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Shi L, Zhang Y, Yang C, Wang Y, Han Y, Li C, Yang Y, Dong D, Du M, Li H. TROAP promotes esophageal squamous cell carcinoma progression via the PI3K/AKT pathway. J Cancer Res Clin Oncol 2025; 151:144. [PMID: 40252097 PMCID: PMC12009240 DOI: 10.1007/s00432-025-06200-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2025] [Accepted: 04/11/2025] [Indexed: 04/21/2025]
Abstract
PURPOSE Trophinin-associated protein (TROAP) plays a crucial role in various human cancers. However, its involvement in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aimed to explore the clinical significance and biological function of TROAP in ESCC. METHODS The expression and clinical relevance of TROAP in ESCC were analyze using GEO and TCGA databases. TROAP expression in ESCC samples was further validated by qRT-PCR, western blotting, and immunohistochemistry. In vitro and in vivo experiments were performed to assess TROAP's role in ESCC progression. RNA-seq analysis followed by western blotting and pathway-specific activator were conducted to explore the underlying mechanism. RESULTS TROAP was found to be overexpressed in ESCC and was positively correlated with higher histological grade and advanced clinical stage. Overexpression of TROAP promoted the proliferation, migration, and invasion of ESCC cells in vitro, whereas knockdown of TROAP suppressed ESCC progression both in vitro and in vivo. Mechanistically, TROAP facilitated ESCC progression by activating PI3K/AKT signaling pathway. CONCLUSION This study revealed that TROAP promotes ESCC progression via activating PI3K/AKT pathway, suggesting that TROAP might be a promising therapeutic target for ESCC.
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Affiliation(s)
- Liqiang Shi
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China
| | - Yajie Zhang
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China
| | - Cong Yang
- Cancer Center, School of Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Yaxin Wang
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China
| | - Yichao Han
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China
| | - Chuanyin Li
- Department of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China
| | - Yun Yang
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Sciences, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China
| | - Dong Dong
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China
| | - Mingyuan Du
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China
| | - Hecheng Li
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China.
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Duan D, Zhou S, Wang Z, Qiao C, Han J, Li M, Zhou H, Li X, Xin W. Genome-Wide Association Study Pinpoints Novel Candidate Genes Associated with the Gestation Length of the First Parity in French Large White Sows. Animals (Basel) 2025; 15:447. [PMID: 39943217 PMCID: PMC11815982 DOI: 10.3390/ani15030447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 01/09/2025] [Accepted: 01/22/2025] [Indexed: 02/16/2025] Open
Abstract
Gestation length (GL) is a critical indicator of reproductive performance in sows and is closely associated with other reproductive traits, such as total number born (TNB) and number born alive (NBA). Despite its importance, the genetic mechanisms underlying GL and its impact on reproductive traits remain poorly understood. In this study, we investigated the relationship between GL and reproductive traits using 7013 farrowing records and conducted an imputed whole-genome sequence-based genome-wide association study (GWAS) for GL in first-parity sows, involving 3005 French Large White sows. Our findings revealed that the heritability of GL ranged from 0.22 to 0.26. Both excessively short and long GLs were associated with negative impacts on TNB, NBA, and other reproductive traits. A total of 64 SNPs exceeded the significance threshold, leading to the identification of two novel quantitative trait loci (QTLs) on chromosome 5 (QTL-1: 15.29-15.39 Mb and QTL-2: 12.86-12.94 Mb) and three promising candidate genes: TROAP, RFX4, and ADCY6. Gene ontology and KEGG pathway enrichment analyses revealed that these candidate genes are enriched in key biological processes, including ovarian steroidogenesis, the GnRH signaling pathway, and the regulation of cAMP biosynthesis, all of which are crucial for gestation and pregnancy maintenance. These findings improve our understanding of the genetic architecture of GL in sows and offer valuable genetic markers for enhancing reproductive efficiency in breeding programs.
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Affiliation(s)
- Dongdong Duan
- Sanya Institute, Hainan Academy of Agricultural Sciences, Sanya 572025, China; (D.D.); (S.Z.); (Z.W.); (C.Q.); (J.H.); (M.L.); (H.Z.)
| | - Shenping Zhou
- Sanya Institute, Hainan Academy of Agricultural Sciences, Sanya 572025, China; (D.D.); (S.Z.); (Z.W.); (C.Q.); (J.H.); (M.L.); (H.Z.)
- Institute of Animal Science and Veterinary Medicine, Hainan Academy of Agricultural Sciences, Haikou 571100, China
| | - Zhenyu Wang
- Sanya Institute, Hainan Academy of Agricultural Sciences, Sanya 572025, China; (D.D.); (S.Z.); (Z.W.); (C.Q.); (J.H.); (M.L.); (H.Z.)
| | - Chuanmin Qiao
- Sanya Institute, Hainan Academy of Agricultural Sciences, Sanya 572025, China; (D.D.); (S.Z.); (Z.W.); (C.Q.); (J.H.); (M.L.); (H.Z.)
| | - Jinyi Han
- Sanya Institute, Hainan Academy of Agricultural Sciences, Sanya 572025, China; (D.D.); (S.Z.); (Z.W.); (C.Q.); (J.H.); (M.L.); (H.Z.)
| | - Mengyu Li
- Sanya Institute, Hainan Academy of Agricultural Sciences, Sanya 572025, China; (D.D.); (S.Z.); (Z.W.); (C.Q.); (J.H.); (M.L.); (H.Z.)
| | - Hao Zhou
- Sanya Institute, Hainan Academy of Agricultural Sciences, Sanya 572025, China; (D.D.); (S.Z.); (Z.W.); (C.Q.); (J.H.); (M.L.); (H.Z.)
| | - Xinjian Li
- Sanya Institute, Hainan Academy of Agricultural Sciences, Sanya 572025, China; (D.D.); (S.Z.); (Z.W.); (C.Q.); (J.H.); (M.L.); (H.Z.)
- Institute of Animal Science and Veterinary Medicine, Hainan Academy of Agricultural Sciences, Haikou 571100, China
| | - Wenshui Xin
- Sanya Institute, Hainan Academy of Agricultural Sciences, Sanya 572025, China; (D.D.); (S.Z.); (Z.W.); (C.Q.); (J.H.); (M.L.); (H.Z.)
- Institute of Animal Science and Veterinary Medicine, Hainan Academy of Agricultural Sciences, Haikou 571100, China
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3
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Qiao Y, Chen Z, Li W, Li H, Zhou L. Clinical significance of TROAP in endometrial cancer and the antiproliferative and proapoptotic effects of TROAP knockdown in endometrial cancer cells: integrated utilization of bioinformatic analysis and in vitro test verification. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:10049-10059. [PMID: 38967825 DOI: 10.1007/s00210-024-03260-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 06/24/2024] [Indexed: 07/06/2024]
Abstract
Trophinin-associated protein (TROAP), a cytoplasmic protein essential for spindle assembly and centrosome integrity during mitosis, has been reported to serve as an oncogene in various tumors. However, its role in endometrial cancer (EC) progression is still undefined. TROAP expression in EC was analyzed via GEPIA and HPA databases. The diagnostic and prognostic values of TROAP were examined by ROC curve analysis and Kaplan-Meier plotter, respectively. Cell proliferation was evaluated using CCK-8 and EdU incorporation assays. Apoptosis was assessed using TUNEL and flow cytometry assays. GSEA was performed to explore TROAP-related pathways in EC. Expression of TROAP, proliferating cell nuclear antigen (PCNA), Ki-67, cleaved-caspase-3 (cl-caspase-3), caspase-3, active β-catenin, and total β-catenin was detected using western blot analysis. TROAP was upregulated in EC. TROAP served as a potential diagnostic and prognostic marker in EC patients. TROAP silencing suppressed proliferation and enhanced apoptosis in EC cells. GSEA revealed that EC and Wnt signaling pathways were related to the expression of TROAP. We further demonstrated that TROAP knockout repressed the Wnt/β-catenin pathway in EC cells. Moreover, SKL2001, a Wnt/β-catenin activator, partially abrogated the effects of TROAP silencing on EC cell proliferation and apoptosis, while the signaling inhibitor XAV-939 had the opposite effect. In conclusion, TROAP knockout retarded proliferation and elicited apoptosis in EC cells by blocking the Wnt/β-catenin pathway.
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Affiliation(s)
- Yan Qiao
- Department of Radiation Oncology, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, 223001, China
| | - Zheng Chen
- Department of Radiation Oncology, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, 223001, China
| | - Wei Li
- Department of Radiation Oncology, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, 223001, China
| | - Hongliang Li
- Department of Radiation Oncology, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, 223001, China
| | - Liqing Zhou
- Department of Radiation Oncology, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, 223001, China.
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Tan Q, Kong P, Chen G, Cai Y, Liu K, Chen C, Mo H, Huang Y, Lu J, Wu Y. Evaluating trophinin associated protein as a biomarker of prognosis and therapy response in renal cell carcinoma. BMC Cancer 2024; 24:1021. [PMID: 39153983 PMCID: PMC11330045 DOI: 10.1186/s12885-024-12802-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Accepted: 08/13/2024] [Indexed: 08/19/2024] Open
Abstract
BACKGROUND Trophinin Associated Protein (TROAP) has been implicated in some tumors, yet its role in renal cell carcinoma (RCC) remains underexplored. This study aims to elucidate the prognostic and therapeutic implications of TROAP in RCC, encompassing different subtypes. METHODS Firstly, we identified the expression patterns of TROAP across various tumors within the TCGA pan-cancer cohort. Subsequently, the prognostic significance of TROAP was validated in three TCGA RCC cohorts and a local cohort. Finally, we conducted functional enrichment analysis, somatic mutations and copy number variations, assessed therapeutic response cohorts, and performed in vitro experiments to explore the biological characteristics of TROAP. RESULTS TROAP serves as an unfavorable factor in both the TCGA RCC datasets and our local cohort. Functional enrichment analysis and in vitro experiments have demonstrated its oncogene effect in promoting tumor progression. Additionally, the relationship between TROAP expression and gene mutations in RCC appears to be limited. Furthermore, elevated TROAP expression is associated with reduced efficacy of RCC therapies, including nivolumab and everolimus. CONCLUSIONS Our findings illustrate TROAP as a pivotal biomarker for prognosis and therapeutic response in RCC. Elevated TROAP expression is indicative of aggressive tumor behavior and resistance to conventional therapies, making it a valuable target for personalized treatment strategies in RCC management.
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Affiliation(s)
- Qinglin Tan
- Department of Oncology, Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, Dongguan Institute of Clinical Cancer Research, The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital), Dongguan, 523059, China
| | - Peiliang Kong
- Department of Pulmonary & Critical Care Medicine, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan, 523059, China
| | - Guobiao Chen
- Department of Thoracic Surgery, The Tenth Affiliated Hospital of Southern Medical University, Dongguan People's Hospital), Dongguan, 523059, China
| | - Yanmin Cai
- Department of Oncology, Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, Dongguan Institute of Clinical Cancer Research, The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital), Dongguan, 523059, China
| | - Kejun Liu
- Department of Oncology, Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, Dongguan Institute of Clinical Cancer Research, The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital), Dongguan, 523059, China
| | - Chen Chen
- Department of Oncology, Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, Dongguan Institute of Clinical Cancer Research, The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital), Dongguan, 523059, China
| | - Huiting Mo
- Department of Oncology, Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, Dongguan Institute of Clinical Cancer Research, The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital), Dongguan, 523059, China
| | - Yuancheng Huang
- Department of Oncology, Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, Dongguan Institute of Clinical Cancer Research, The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital), Dongguan, 523059, China
| | - Jianming Lu
- Center for medical research on innovation and translation, Institute of Clinical Medicine, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China
| | - Yifen Wu
- Department of Oncology, Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, Dongguan Institute of Clinical Cancer Research, The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital), Dongguan, 523059, China.
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Tu C, Liu B, Li C, Feng C, Wang H, Zhang H, He S, Li Z. Integrative analysis of TROAP with molecular features, carcinogenesis, and related immune and pharmacogenomic characteristics in soft tissue sarcoma. MedComm (Beijing) 2023; 4:e369. [PMID: 37731946 PMCID: PMC10507284 DOI: 10.1002/mco2.369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 07/30/2023] [Accepted: 08/18/2023] [Indexed: 09/22/2023] Open
Abstract
Soft tissue sarcoma (STS) is an uncommon malignancy that often carries a grim prognosis. Trophinin-associated protein (TROAP) is augmented in a variety of tumors and can affect tumor proliferation. Nevertheless, the prognostic value and specific functions of TROAP in STS are still vague. Herein, we display that TROAP exhibits an augmented trend in STS, and its elevation correlates with a poor prognosis of STS. Furthermore, its reduction is related to increased immune cell infiltration, enhanced stroma, and elevation of immune activation. Meanwhile, the TROAP-derived genomic signature is validated to predict patient prognosis, immunotherapy, and drug response reliably. A nomogram constructed based on age, metastatic status, and a TROAP-derived risk score of an STS individual could be used to quantify the survival probability of STS. In addition, in vitro experiments have demonstrated that TROAP is overexpressed in STS, and the downregulation of TROAP could affect the proliferation, migration, metastasis, and cell cycle of STS cells. In summary, the TROAP expression is elevated in STS tissues and cells, which is related to the poor prognosis and malignant biological behaviors of STS. It could act as a potential prognostic biomarker for diagnosis and treatment of STS.
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Affiliation(s)
- Chao Tu
- Department of OrthopaedicsThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina
- Hunan Key Laboratory of Tumor Models and Individualized MedicineThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina
- Shenzhen Research Institute of Central South UniversityGuangdongChina
| | - Binfeng Liu
- Department of OrthopaedicsThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina
- Hunan Key Laboratory of Tumor Models and Individualized MedicineThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina
| | - Chenbei Li
- Department of OrthopaedicsThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina
- Hunan Key Laboratory of Tumor Models and Individualized MedicineThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina
| | - Chengyao Feng
- Department of OrthopaedicsThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina
- Hunan Key Laboratory of Tumor Models and Individualized MedicineThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina
| | - Hua Wang
- Department of OrthopaedicsThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina
- Hunan Key Laboratory of Tumor Models and Individualized MedicineThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina
| | - Haixia Zhang
- Department of OncologyThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina
| | - Shasha He
- Department of OncologyThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina
| | - Zhihong Li
- Department of OrthopaedicsThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina
- Hunan Key Laboratory of Tumor Models and Individualized MedicineThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina
- Shenzhen Research Institute of Central South UniversityGuangdongChina
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Xu M, Yu J, Liu X, Jia W, Duan Y, Ma D, Ma J, Lei W, Tai W. METTL3 regulatory TROAP can regulate the progression of non-small cell lung cancer through PI3K/AKT and EMT signaling pathway. Med Oncol 2023; 40:274. [PMID: 37608033 DOI: 10.1007/s12032-023-02143-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 07/29/2023] [Indexed: 08/24/2023]
Abstract
TROAP, interacts with trophinin and bystin, polys a key role in embryo implantation. TROAP is required for spindle assembly and centrosome integrity during the mitosis. TROAP has been described to promote tumorigenesis in a diverse range of cancer. We performed this study to assess the biological and clinical significance of TROAP in Non-small cell lung cancer. Forty-eight pairs of lung adenocarcinoma (LUAD) tissues and paraneoplastic tissues were collected. RT-qPCR, western bolt and immunohistochemistry assay was used to test TROAP RNA and protein expression not in LUAD tissues and paraneoplastic tissues but in LUAD cell lines and control cell lines. TROAP knockdown and overexpression vector were constructed and transfected into lung cancer cells. CCK-8, transwell, and wound healing assays were used to assess cell viability, migration, and invasion. The expression of PI3K/AKT and EMT signaling proteins and METTL3 were determined by western blot. We found the TROAP was enriched in NSCLC tissues and cell lines. TROAP knockdown inhibited cell proliferation, migration, invasion compared with control group in NSCLC. Mechanism analysis revealed that TROAP activated PI3K/AKT and EMT signaling pathway. To a certain extent, TROAP was regulated by METTL3. In a word, TROAP accelerated the progression of NSCLC through PI3K/AKT and EMT pathway, and TROAP might be considered as a novel target for NSCLC therapy.
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Affiliation(s)
- Muli Xu
- Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Jiankun Yu
- Chinese Academy of Medical Sciences and Institute of Medical Biology, Peking Union Medical College, Kunming, China
| | - Xiaoxiao Liu
- Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Wanting Jia
- Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Yu Duan
- Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Di Ma
- Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Jiaxuan Ma
- Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Wanyang Lei
- Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Wenlin Tai
- Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
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Wang J, Wan H, Mi Y, Wu S, Li J, Zhu L. TROAP Promotes the Proliferation, Migration, and Metastasis of Kidney Renal Clear Cell Carcinoma with the Help of STAT3. Int J Mol Sci 2023; 24:9658. [PMID: 37298609 PMCID: PMC10253451 DOI: 10.3390/ijms24119658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 05/29/2023] [Accepted: 05/31/2023] [Indexed: 06/12/2023] Open
Abstract
Kidney renal clear cell carcinoma (KIRC) is a subtype of renal cell carcinoma that threatens human health. The mechanism by which the trophinin-associated protein (TROAP)-an important oncogenic factor-functions in KIRC has not been studied. This study investigated the specific mechanism by which TROAP functions in KIRC. TROAP expression in KIRC was analyzed using the RNAseq dataset from the Cancer Genome Atlas (TCGA) online database. The Mann-Whitney U test was used to analyze the expression of this gene from clinical data. The Kaplan-Meier method was used for the survival analysis of KIRC. The expression level of TROAP mRNA in the cells was detected using qRT-PCR. The proliferation, migration, apoptosis, and cell cycle of KIRC were detected using Celigo, MTT, wound healing, cell invasion assay, and flow cytometry. A mouse subcutaneous xenograft experiment was designed to demonstrate the effect of TROAP expression on KIRC growth in vivo. To further investigate the regulatory mechanism of TROAP, we performed co-immunoprecipitation (CO-IP) and shotgun liquid chromatography-tandem mass spectrometry (LC-MS). TCGA-related bioinformatics analysis showed that TROAP was significantly overexpressed in KIRC tissues and was related to higher T and pathological stages, and a poor prognosis. The inhibition of TROAP expression significantly reduced the proliferation of KIRC, affected the cell cycle, promoted cell apoptosis, and reduced cell migration and invasion. The subcutaneous xenograft experiments showed that the size and weight of the tumors in mice were significantly reduced after TROAP-knockdown. CO-IP and post-mass spectrometry bioinformatics analyses revealed that TROAP may combine with signal transducer and activator of transcription 3 (STAT3) to achieve tumor progression in KIRC; this was verified by functional recovery experiments. TROAP may regulate KIRC proliferation, migration, and metastasis by binding to STAT3.
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Affiliation(s)
- Jun Wang
- Department of Urology, Affiliated Hospital of Jiangnan University, Wuxi 214122, China (Y.M.)
- Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210008, China
| | - Hongyuan Wan
- Department of Urology, Affiliated Hospital of Jiangnan University, Wuxi 214122, China (Y.M.)
- Wuxi Medical College, Jiangnan University, Wuxi 214122, China
| | - Yuanyuan Mi
- Department of Urology, Affiliated Hospital of Jiangnan University, Wuxi 214122, China (Y.M.)
| | - Sheng Wu
- Department of Urology, Affiliated Hospital of Jiangnan University, Wuxi 214122, China (Y.M.)
| | - Jie Li
- Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210008, China
| | - Lijie Zhu
- Department of Urology, Affiliated Hospital of Jiangnan University, Wuxi 214122, China (Y.M.)
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He X, Hu J, Yan C, Liu X, Zhao Y, Yang P, Wang J, Li S, Zhang W, Dong G, Zhang W, Jing H. High trophinin-associated protein expression predicts good survival in acute myeloid leukemia with normal cytogenetics. Cancer Biomark 2023; 36:221-230. [PMID: 36938721 DOI: 10.3233/cbm-210042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
BACKGROUND Nearly half of adult acute myeloid leukemia (AML) patients were classified into cytogenetic normal acute myeloid leukemia (CN-AML). The expression level of Trophinin associated protein (TROAP) was proven to be associated with the prognosis of several cancers, but it is still unclear in the prognosis of patients with CN-AML. METHODS We integrated CN-AML patients samples from 4 datasets to analyze the relationship between TROAP expression and the survival of CN-AML. In addition, we investigated 92 AML patients of The Cancer Genome Atlas (TCGA) database to analyze the relationship between TROAP expression and the survival of AML patients received chemotherapy. We investigated the relationship between the expression of TROAP and drug sensitivity in AML cell lines. RESULTS CN-AML patients with high TROAP expression were related to good event-free survival (EFS) and overall survival (OS). In AML patients received chemotherapy, high TROAP expression was associated with good survival prognosis. Additionally, the expression of TROAP gene in leukemia stem cells (LSC) + group was lower. Among multiple drugs, the lower the expression of TROAP, the lower the IC50. CONCLUSION TROAP could serve as an independent predictor of CN-AML patients and could act as a potential biomarker for the prognosis of CN-AML. TROAP expression levels were closely correlated with the drug sensitivity of multiple drugs.
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Affiliation(s)
- Xue He
- Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,Department of Pathology, Capital Medical University, Beijing, China.,Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Jing Hu
- Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing, China.,Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Changjian Yan
- The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China.,Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Xiaoni Liu
- Department of Respiratory Medicine, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
| | - Yali Zhao
- General Practice Medicine, The First People's Hospital of Huzhou, Huzhou, Zhejiang, China
| | - Ping Yang
- Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing, China
| | - Jing Wang
- Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing, China
| | - Shaoxiang Li
- Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,Department of Pathology, Capital Medical University, Beijing, China
| | - Wei Zhang
- Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,Department of Pathology, Capital Medical University, Beijing, China
| | - Gehong Dong
- Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,Department of Pathology, Capital Medical University, Beijing, China
| | - Weilong Zhang
- Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing, China
| | - Hongmei Jing
- Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing, China
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Siriwardena D, Boroviak TE. Evolutionary divergence of embryo implantation in primates. Philos Trans R Soc Lond B Biol Sci 2022; 377:20210256. [PMID: 36252209 DOI: 10.1098/rstb.2021.0256] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Implantation of the conceptus into the uterus is absolutely essential for successful embryo development. In humans, our understanding of this process has remained rudimentary owing to the inaccessibility of early implantation stages. Non-human primates recapitulate many aspects of human embryo development and provide crucial insights into trophoblast development, uterine receptivity and embryo invasion. Moreover, primate species exhibit a variety of implantation strategies and differ in embryo invasion depths. This review examines conservation and divergence of the key processes required for embryo implantation in different primates and in comparison with the canonical rodent model. We discuss trophectoderm compartmentalization, endometrial remodelling and embryo adhesion and invasion. Finally, we propose that studying the mechanism controlling invasion depth between different primate species may provide new insights and treatment strategies for placentation disorders in humans. This article is part of the theme issue 'Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom'.
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Affiliation(s)
- Dylan Siriwardena
- Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.,Centre for Trophoblast Research, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.,Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge CB2 0AW, UK
| | - Thorsten E Boroviak
- Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.,Centre for Trophoblast Research, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.,Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge CB2 0AW, UK
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10
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Li Z, Pu Z, Yang Z, Zhu Y, Deng Y, Li N, Peng F. Pan-cancer analysis of trophinin-associated protein with potential implications in clinical significance, prognosis, and tumor microenvironment in human cancers. Front Oncol 2022; 12:971618. [PMID: 36419876 PMCID: PMC9677944 DOI: 10.3389/fonc.2022.971618] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 10/13/2022] [Indexed: 08/24/2023] Open
Abstract
BACKGROUND Trophinin-associated protein (TROAP), a cytoplasmic protein, is essential for microtubule cytoskeleton assembly. Mounting evidence demonstrates the vital role of TROAP in regulating the proliferation and migration of cells, but it is unclear how it contributes to cancer progression. METHODS The online portals of GEPIA2, Cancer Cell Line Encyclopedia, UALCAN, Human Protein Atlas, and PrognoScan were used to analyze TROAP expression in various tumors and further evaluate its correlation with prognosis. With Western blot and quantitative real-time PCR analysis, we validated TROAP expression levels in hepatocellular carcinoma (HCC) and colorectal cancer (CRC). Ten pairs of HCC and CRC tissues were selected for immunohistochemistry to determine TROAP expression levels in tumors and adjacent tissues, respectively. TROAP knockdown in CRC and HCC cells to verify its role in malignant phenotypes. The genomic and post-transcriptional alterations of TROAP in tumors were determined using the cBioPortal and SangerBox databases. Also, TISIDB was used to investigate the relationship between TROAP expression and tumor microenvironment(TME) among different cancer types. Moreover, a correlation was found between the expression of TROAP and drug sensitivity using GSCALite and CellMiner databases. RESULTS TROAP expression was significantly upregulated in most cancer types, which is consistent with our validated experimental results in HCC and CRC cells, and immunohistochemistry results. And a poor prognosis was linked to TROAP aberrant expression. Our findings indicated that malignant phenotypes and tumorigenesis induced by TROAP could be due to an activation of the PI3K/Akt/GSK-3β signaling pathway. Furthermore, we found a correlation between TROAP expression and genomic and post-transcriptional alterations in various tumors, including tumor mutation burden, and microsatellite instability. Next, we demonstrated that TROAP expression was associated with the infiltration of immune cells, such as neutrophils and macrophages, and correlated with immunomodulation-related genes in the TME. Additionally, the potential role of TROAP expression in predicting the sensitivity of drugs, including melphalan and chlorambucil, was demonstrated. CONCLUSIONS Collectively, these findings indicated a significant correlation between TROAP expression and malignant phenotype, functional mechanism, survival possibility, TME, therapeutic potential, and prediction of drug sensitivity in various cancers. Hence, TROAP is a promising biomarker and therapeutic target for predicting cancer outcomes.
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Affiliation(s)
- Zhenfen Li
- Department of Blood Transfusion, Clinical Transfusion Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Health Commission (NHC) Key Laboratory of Cancer Proteomics, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Zhangya Pu
- Department of Infectious Diseases and Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
| | - Ziyue Yang
- Department of Blood Transfusion, Clinical Transfusion Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Health Commission (NHC) Key Laboratory of Cancer Proteomics, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yuanyuan Zhu
- Department of Blood Transfusion, Clinical Transfusion Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Health Commission (NHC) Key Laboratory of Cancer Proteomics, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Ying Deng
- Department of Scientific Research Management, Ningxiang People’s Hospital, Hunan University Traditional Chinese Medicine, Ningxiang, Changsha, Hunan, China
| | - Ning Li
- Department of Blood Transfusion, Clinical Transfusion Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Fang Peng
- Department of Blood Transfusion, Clinical Transfusion Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Health Commission (NHC) Key Laboratory of Cancer Proteomics, Xiangya Hospital, Central South University, Changsha, Hunan, China
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11
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Zhao P, Du H, Jiang L, Zheng X, Feng W, Diao C, Zhou L, Liu GE, Zhang H, Chamba Y, Zhang Q, Li B, Liu JF. PRE-1 Revealed Previous Unknown Introgression Events in Eurasian Boars during the Middle Pleistocene. Genome Biol Evol 2021; 12:1751-1764. [PMID: 33151306 PMCID: PMC7643367 DOI: 10.1093/gbe/evaa142] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/03/2020] [Indexed: 12/22/2022] Open
Abstract
Introgression events and population admixture occurred among Sus species across the Eurasian mainland in the Middle Pleistocene, which reflects the local adaption of different populations and contributes to evolutionary novelty. Previous findings on these population introgressions were largely based on extensive genome-wide single-nucleotide polymorphism information, ignoring structural variants (SVs) as an important alternative resource of genetic variations. Here, we profiled the genome-wide SVs and explored the formation of pattern-related SVs, indicating that PRE1-SS is a recently active subfamily that was strongly associated with introgression events in multiple Asian and European pig populations. As reflected by the three different combination haplotypes from two specific patterns and known phylogenetic relationships in Eurasian boars, we identified the Asian Northern wild pigs as having experienced introgression from European wild boars around 0.5–0.2 Ma and having received latitude-related selection. During further exploration of the influence of pattern-related SVs on gene functions, we found substantial sequence changes in 199 intron regions of 54 genes and 3 exon regions of 3 genes (HDX, TRO, and SMIM1), implying that the pattern-related SVs were highly related to positive selection and adaption of pigs. Our findings revealed novel introgression events in Eurasian wild boars, providing a timeline of population admixture and divergence across the Eurasian mainland in the Middle Pleistocene.
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Affiliation(s)
- Pengju Zhao
- National Engineering Laboratory for Animal Breeding; Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture; College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Heng Du
- National Engineering Laboratory for Animal Breeding; Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture; College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Lin Jiang
- Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, China
| | - Xianrui Zheng
- National Engineering Laboratory for Animal Breeding; Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture; College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Wen Feng
- National Engineering Laboratory for Animal Breeding; Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture; College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Chenguang Diao
- National Engineering Laboratory for Animal Breeding; Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture; College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Lei Zhou
- National Engineering Laboratory for Animal Breeding; Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture; College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - George E Liu
- Animal Genomics and Improvement Laboratory, BARC, USDA-ARS, Maryland
| | - Hao Zhang
- National Engineering Laboratory for Animal Breeding; Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture; College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Yangzom Chamba
- College of Animal Science and Technology, Tibet Agriculture and Animal Husbandry College, Linzhi, Tibet, China
| | - Qin Zhang
- National Engineering Laboratory for Animal Breeding; Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture; College of Animal Science and Technology, China Agricultural University, Beijing, China.,College of Animal Science and Technology, Shandong Agricultural University, Taian, Shandong, PR China
| | - Bugao Li
- Department of Animal Sciences and Veterinary Medicine, Shanxi Agricultural University, Taigu, China
| | - Jian-Feng Liu
- National Engineering Laboratory for Animal Breeding; Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture; College of Animal Science and Technology, China Agricultural University, Beijing, China
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12
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Gao B, Wang L, Zhang Y, Zhang N, Han M, Liu H, Sun D, Liu Y. MiR-532-3p suppresses cell viability, migration and invasion of clear cell renal cell carcinoma through targeting TROAP. Cell Cycle 2021; 20:1578-1588. [PMID: 34287099 DOI: 10.1080/15384101.2021.1953767] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
Clear cell renal cell carcinoma (ccRCC) is a subtype of renal cell cancer with the highest mortality, infiltration, and metastasis rate, threatening human health. Despite oncogenic role of TROAP in various cancers, its function in ccRCC remains to be unraveled. The differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) were obtained by analyzing the related data sets of ccRCC in TCGA. The expression levels of mRNAs and miRNAs in the cell were detected by qRT-PCR, while the protein levels were characterized by western blot. The viability, migratory and invasive abilities of ccRCC cells were determined by MTT, wound healing and cell invasion assays. The combination of miRNA target site prediction and dual-luciferase reporter gene assay verified the binding relationship between miR-532-3p and TROAP. Research on ccRCC displayed that TROAP expression was upregulated, while miR-532-3p was down-regulated. Besides, upregulation of TROAP could accelerate viability, migratory and invasive potentials of ccRCC cells. On the contrary, miR-532-3p could downregulate TROAP level, but TROAP upregulation reversed the viability, migration, and invasion of ccRCC cells. MiR-532-3p could attenuate the viability, migration and invasion of ccRCC cells by targeting TROAP. This may generate novel insights into molecular therapeutic targets for ccRCC.
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Affiliation(s)
- Bin Gao
- Department of Urology, Tangshan Central Hospital, Tangshan, Hebei, P.R. China
| | - Lijuan Wang
- Department of Urology, Tangshan Central Hospital, Tangshan, Hebei, P.R. China
| | - Yubo Zhang
- Department of Urology, Tangshan Central Hospital, Tangshan, Hebei, P.R. China
| | - Na Zhang
- Department of Urology, Tangshan Central Hospital, Tangshan, Hebei, P.R. China
| | - Miaomiao Han
- Department of Urology, Tangshan Central Hospital, Tangshan, Hebei, P.R. China
| | - Huancai Liu
- Department of Urology, Tangshan Central Hospital, Tangshan, Hebei, P.R. China
| | - Dongli Sun
- Department of Urology, Tangshan Central Hospital, Tangshan, Hebei, P.R. China
| | - Yifei Liu
- Department of Urology, Tangshan Central Hospital, Tangshan, Hebei, P.R. China
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13
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Shinkai Y, Kuramochi M, Miyafusa T. New Family Members of FG Repeat Proteins and Their Unexplored Roles During Phase Separation. Front Cell Dev Biol 2021; 9:708702. [PMID: 34322491 PMCID: PMC8311347 DOI: 10.3389/fcell.2021.708702] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 06/17/2021] [Indexed: 12/26/2022] Open
Abstract
The condensation and compartmentalization of biomacromolecules in the cell are driven by the process of phase separation. The main effectors of phase separation are intrinsically disordered proteins, which include proteins with a phenylalanine-glycine (FG) repeat domain. Our understanding of the biological function of FG repeat proteins during phase separation has been mainly derived from recent research on a member of the nuclear pore complex proteins, nucleoporins containing FG repeat domain (FG-NUPs). FG-NUPs form meshwork structures by inter- and intra-molecular FG domain interactions, which confine the nucleo-cytoplasmic exchange. Whereas FG-NUPs localize in the nuclear membrane, other FG repeat proteins reside in the cytoplasm and the nucleoplasm, and the biological function of the FG repeat domain of these proteins is not well described. In the present review, we list the FG repeat proteins that are known to phase separate in the cell, and review their biological functions. We extract the unraveled features of FG repeat proteins as an activator of barrier formation and homotypic cell-cell interactions. Understanding the regulatory mechanisms of FG repeat proteins will provide a potential delivery tool for therapeutic reagents.
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Affiliation(s)
- Yoichi Shinkai
- Molecular Neurobiology Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
| | - Masahiro Kuramochi
- Graduate School of Science and Engineering, Ibaraki University, Hitachi, Japan
| | - Takamitsu Miyafusa
- Bio-System Research Group, Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
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14
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Zhao Z, Wu X, Cheng Y, Zhou Y, Ma X, Zhang J, Heng X, Feng F. TROAP regulates cell cycle and promotes tumor progression through Wnt/β-Catenin signaling pathway in glioma cells. CNS Neurosci Ther 2021; 27:1064-1076. [PMID: 34077623 PMCID: PMC8339535 DOI: 10.1111/cns.13688] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 05/02/2021] [Accepted: 05/17/2021] [Indexed: 12/28/2022] Open
Abstract
AIMS Experimental evidence demonstrated a crucial role of TROAP (Trophinin-associated protein) in regulating the cell proliferation of multiple tumors, while TROAP expression and function were largely unknown in glioma. We aimed to investigate the oncogenic role of TROAP and its potential mechanisms in gliomagenesis. METHODS Four gene expression databases (GEO, TCGA, GTEx and CCLE) were enrolled in our study and used for TROAP expression and survival analysis. TROAP expression was quantified by qRT-PCR, western blot and immunohistochemistry assays in glioma tissues and cell lines. TROAP knockdown and overexpression vector were constructed and transfected into glioma cells. CCK-8, colony formation, transwell, and wound healing assays were used to evaluate cell viability, migration and invasion, flow cytometry to determine cell cycle arrest. Gene set enrichment analysis (GSEA) was conducted to screen the pathway involved in TROAP-high phenotype. The expression of cell cycle and Wnt/β-Catenin signaling proteins were analyzed by immunofluorescence and western blot. RESULTS Based on the bioinformatic analysis and a series of functional assays, we found the TROAP was enriched in glioma tissues and cell lines, its overexpression was correlated with the clinicopathologic characteristics and poor prognosis. TROAP knockdown inhibited cell proliferation, migration, invasion, and G1/S cell cycle arrest compared with control group in glioma. Mechanism analysis revealed that TROAP activated Wnt/β-Catenin pathway and upregulated its downstream targets expression, while silencing β-Catenin or Axin2 could reverse the tumor-promoting effects caused by TROAP, confirming that TROAP-induced malignant phenotype and tumorigenesis via Wnt/β-Catenin signaling pathway. CONCLUSION The present study found that TROAP accelerated the progression of gliomagenesis through Wnt/β-Catenin pathway, and TROAP might be considered as a novel target for glioma therapy.
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Affiliation(s)
- Zong‐qing Zhao
- Department of NeurosurgeryLinyi People’s HospitalLinyiChina
- Institute of Brain Science and Brain‐Like IntelligenceLinyi People’s HospitalLinyiChina
| | - Xiu‐jie Wu
- Department of NeurosurgeryLinyi People’s HospitalLinyiChina
- Institute of Brain Science and Brain‐Like IntelligenceLinyi People’s HospitalLinyiChina
| | - Yan‐hao Cheng
- Department of NeurosurgeryLinyi People’s HospitalLinyiChina
- Institute of Brain Science and Brain‐Like IntelligenceLinyi People’s HospitalLinyiChina
| | - Yun‐fei Zhou
- Institute of Brain Science and Brain‐Like IntelligenceLinyi People’s HospitalLinyiChina
| | - Xi‐meng Ma
- Institute of Brain Science and Brain‐Like IntelligenceLinyi People’s HospitalLinyiChina
| | - Jian Zhang
- Department of NeurosurgeryLinyi People’s HospitalLinyiChina
- Institute of Brain Science and Brain‐Like IntelligenceLinyi People’s HospitalLinyiChina
| | - Xue‐yuan Heng
- Department of NeurosurgeryLinyi People’s HospitalLinyiChina
- Institute of Brain Science and Brain‐Like IntelligenceLinyi People’s HospitalLinyiChina
| | - Fan Feng
- Department of NeurosurgeryLinyi People’s HospitalLinyiChina
- Institute of Brain Science and Brain‐Like IntelligenceLinyi People’s HospitalLinyiChina
- Institute of Clinical Medicine CollegeGuangzhou University of Chinese MedicineGuangzhouChina
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15
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Jin L, Zhou Y, Chen G, Dai G, Fu K, Yang D, Zhu J. EZH2-TROAP Pathway Promotes Prostate Cancer Progression Via TWIST Signals. Front Oncol 2021; 10:592239. [PMID: 33692939 PMCID: PMC7938320 DOI: 10.3389/fonc.2020.592239] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 12/31/2020] [Indexed: 12/27/2022] Open
Abstract
Trophinin-associated protein (TROAP) has been shown to be overexpressed and promotes tumor progression in some tumors. We performed this study to assess the biological and clinical significance of TROAP in prostate cancer. We downloaded TROAP mRNA expression data from TCGA and GEO databases. We analyzed expressions of TROAP and other genes in prostate cancer tumors at different stages and assessed Gleason scores. We used Celigo image, Transwell, and rescue assays, and flow cytometry detection to assess growth, apoptosis, proliferation, migration, and invasion of the prostate cancer cells. We identified and validated up- and down-stream genes in the TROAP pathway. The mRNA data suggested that TROAP expression was markedly upregulated in prostate cancer compared with its expression in normal tissues, especially in cancers with high stages and Gleason scores. Moreover, a high TROAP expression was associated with poor patient survival. Results of our in vitro assay showed that TROAP knockdown inhibited DU145 and PC3 cell proliferation and viability via cell apoptosis and S phase cycle arrest. The Transwell assay showed that TROAP knockdown inhibited cell migration and invasion, probably through MMP-9 and E-Cadherin modulation. Overexpression of TWIST partially abrogated the inhibitory effects of TROAP knockdown on prostate cancer cells. Our integrative mechanism dissection revealed that TROAP is in a pathway downstream of EZH2 and that it activates the TWIST/c-Myc pathway to regulate prostate cancer progression. In all, we identified TROAP as a driver of prostate cancer development and progression, providing a novel target for prostate cancer treatments.
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Affiliation(s)
- Lu Jin
- Department of Urology, Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yibin Zhou
- Department of Urology, Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Guangqiang Chen
- Department of Radiology, Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Guangcheng Dai
- Department of Urology, Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Kai Fu
- Department of Urology, Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Dongrong Yang
- Department of Urology, Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Jin Zhu
- Department of Urology, Second Affiliated Hospital of Soochow University, Suzhou, China
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16
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Li L, Wei JR, Song Y, Fang S, Du Y, Li Z, Zeng TT, Zhu YH, Li Y, Guan XY. TROAP switches DYRK1 activity to drive hepatocellular carcinoma progression. Cell Death Dis 2021; 12:125. [PMID: 33500384 PMCID: PMC7838256 DOI: 10.1038/s41419-021-03422-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/17/2020] [Accepted: 12/21/2020] [Indexed: 12/24/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the common malignancy and lacks effective therapeutic targets. Here, we demonstrated that ectopic expression of trophinin-associated protein (TROAP) dramatically drove HCC cell growth assessed by foci formation in monolayer culture, colony formation in soft agar and orthotopic liver transplantation in nude mice. Inversely, silencing TROAP expression with short-hairpin RNA attenuated the malignant proliferation of HCC cells in vitro and in vivo. Next, mechanistic investigation revealed that TROAP directly bound to dual specificity tyrosine phosphorylation regulated kinase 1A/B (DYRK1A/B), resulting in the cytoplasmic retention of proteins DYRK1A/B and promoting cell cycle process via activation of Akt/GSK-3β signaling. Combination of cisplatin with an inhibitor of DYRK1 AZ191 effectively inhibited tumor growth in mouse model for HCC cells with high level of TROAP. Clinically, TROAP was significantly upregulated by miR-142-5p in HCC tissues, which predicted the poor survival of patients with HCC. Therefore, TROAP/DYRK1/Akt axis may be a promising therapeutic target and prognostic indicator for patients with HCC.
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Affiliation(s)
- Lei Li
- State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 510060, Guangzhou, China.
- Department of Clinical Oncology, State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.
- Department of Clinical Oncology Center, The University of Hongkong-Shenzhen Hospital, 518053, Shenzhen, China.
| | - Jia-Ru Wei
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, China
| | - Ye Song
- Affiliated Cancer Hospital & Institutes of Guangzhou Medical University, Guangzhou Key Medical Discipline Construction Project, 510095, Guangzhou, China
| | - Shuo Fang
- The Seventh Affiliated Hospital, Sun Yat-sen University, 518100, Shenzhen, China
| | - Yanyu Du
- The Seventh Affiliated Hospital, Sun Yat-sen University, 518100, Shenzhen, China
| | - Zhuo Li
- State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 510060, Guangzhou, China
| | - Ting-Ting Zeng
- State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 510060, Guangzhou, China
| | - Ying-Hui Zhu
- State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 510060, Guangzhou, China
| | - Yan Li
- State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 510060, Guangzhou, China
| | - Xin-Yuan Guan
- State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 510060, Guangzhou, China.
- Department of Clinical Oncology, State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.
- Department of Clinical Oncology Center, The University of Hongkong-Shenzhen Hospital, 518053, Shenzhen, China.
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17
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D'Occhio MJ, Campanile G, Zicarelli L, Visintin JA, Baruselli PS. Adhesion molecules in gamete transport, fertilization, early embryonic development, and implantation-role in establishing a pregnancy in cattle: A review. Mol Reprod Dev 2020; 87:206-222. [PMID: 31944459 DOI: 10.1002/mrd.23312] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 12/19/2019] [Indexed: 12/11/2022]
Abstract
Cell-cell adhesion molecules have critically important roles in the early events of reproduction including gamete transport, sperm-oocyte interaction, embryonic development, and implantation. Major adhesion molecules involved in reproduction include cadherins, integrins, and disintegrin and metalloprotease domain-containing (ADAM) proteins. ADAMs on the surface of sperm adhere to integrins on the oocyte in the initial stages of sperm-oocyte interaction and fusion. Cadherins act in early embryos to organize the inner cell mass and trophectoderm. The trophoblast and uterine endometrial epithelium variously express cadherins, integrins, trophinin, and selectin, which achieve apposition and attachment between the elongating conceptus and uterine epithelium before implantation. An overview of the major cell-cell adhesion molecules is presented and this is followed by examples of how adhesion molecules help shape early reproductive events. The argument is made that a deeper understanding of adhesion molecules and reproduction will inform new strategies that improve embryo survival and increase the efficiency of natural mating and assisted breeding in cattle.
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Affiliation(s)
- Michael J D'Occhio
- School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia
| | - Giuseppe Campanile
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Naples, Italy
| | - Luigi Zicarelli
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Naples, Italy
| | - José A Visintin
- Department of Animal Reproduction, Faculty of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo, Brazil
| | - Pietro S Baruselli
- Department of Animal Reproduction, Faculty of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo, Brazil
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18
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He Y, Chang Y, Bao L, Yu M, Li R, Niu J, Fan G, Song W, Seim I, Qin Y, Li X, Liu J, Kong X, Peng M, Sun M, Wang M, Qu J, Wang X, Liu X, Wu X, Zhao X, Wang X, Zhang Y, Guo J, Liu Y, Liu K, Wang Y, Zhang H, Liu L, Wang M, Yu H, Wang X, Cheng J, Wang Z, Xu X, Wang J, Yang H, Lee SMY, Liu X, Zhang Q, Qi J. A chromosome-level genome of black rockfish, Sebastes schlegelii, provides insights into the evolution of live birth. Mol Ecol Resour 2019; 19:1309-1321. [PMID: 31077549 DOI: 10.1111/1755-0998.13034] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 04/29/2019] [Accepted: 05/06/2019] [Indexed: 12/26/2022]
Abstract
The black rockfish (Sebastes schlegelii) is a teleost in which eggs are fertilized internally and retained in the maternal reproductive system, where they undergo development until live birth (viviparity). In the present study, we report a chromosome-level black rockfish genome assembly. High-throughput transcriptome analysis (RNA-seq and ATAC-seq) coupled with in situ hybridization (ISH) and immunofluorescence reveal several candidate genes for maternal preparation, sperm storage and release, and hatching. We propose that zona pellucida (ZP) proteins retain sperm at the oocyte envelope, while genes in two distinct astacin metalloproteinase subfamilies serve to release sperm from the ZP and free the embryo from chorion at prehatching stage. We present a model of black rockfish reproduction, and propose that the rockfish ovarian wall has a similar function to the uterus of mammals. Together, these genomic data reveal unprecedented insights into the evolution of an unusual teleost life history strategy, and provide a sound foundation for studying viviparity in nonmammalian vertebrates and an invaluable resource for rockfish ecological and evolutionary research.
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Affiliation(s)
- Yan He
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China.,Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Yue Chang
- BGI-Shenzhen, Shenzhen, China.,BGI-Qingdao, BGI-Shenzhen, Qingdao, China
| | - Lisui Bao
- The University of Chicago, Chicago, Illinois
| | - Mengjun Yu
- BGI-Qingdao, BGI-Shenzhen, Qingdao, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, China
| | - Rui Li
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Jingjing Niu
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Guangyi Fan
- BGI-Qingdao, BGI-Shenzhen, Qingdao, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, China.,State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, Macao, China
| | - Weihao Song
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Inge Seim
- Integrative Biology Laboratory, College of Life Sciences, Nanjing Normal University, Nanjing, China.,Comparative and Endocrine Biology Laboratory, Translational Research Institute-Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia
| | - Yating Qin
- BGI-Qingdao, BGI-Shenzhen, Qingdao, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, China
| | - Xuemei Li
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Jinxiang Liu
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Xiangfu Kong
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Meiting Peng
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Minmin Sun
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Mengya Wang
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Jiangbo Qu
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Xuangang Wang
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Xiaobing Liu
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Xiaolong Wu
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Xi Zhao
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Xuliang Wang
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Yaolei Zhang
- BGI-Qingdao, BGI-Shenzhen, Qingdao, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, China
| | - Jiao Guo
- BGI-Qingdao, BGI-Shenzhen, Qingdao, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, China
| | - Yang Liu
- BGI-Qingdao, BGI-Shenzhen, Qingdao, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, China
| | - Kaiqiang Liu
- BGI-Qingdao, BGI-Shenzhen, Qingdao, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, China
| | - Yilin Wang
- BGI-Qingdao, BGI-Shenzhen, Qingdao, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, China
| | - He Zhang
- BGI-Qingdao, BGI-Shenzhen, Qingdao, China.,Department of Biology, Hong Kong Baptist University, Hong Kong, China
| | - Longqi Liu
- BGI-Shenzhen, Shenzhen, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, China
| | - Mingyue Wang
- BGI-Shenzhen, Shenzhen, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, China
| | - Haiyang Yu
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Xubo Wang
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Jie Cheng
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Zhigang Wang
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Xun Xu
- BGI-Shenzhen, Shenzhen, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, China
| | - Jian Wang
- BGI-Shenzhen, Shenzhen, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, China
| | - Huanming Yang
- BGI-Shenzhen, Shenzhen, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, China
| | - Simon Ming-Yuen Lee
- State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, Macao, China
| | - Xin Liu
- BGI-Qingdao, BGI-Shenzhen, Qingdao, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, China.,BGI-Fuyang, BGI-Shenzhen, Fuyang, China
| | - Quanqi Zhang
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China.,Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Jie Qi
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China
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19
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Ma X, Li P, Zhang Q, He L, Su G, Huang Y, Lu Z, Hu W, Ding H, Huang R. Transcriptome analysis of the endometrium from Chinese Erhualian sows that differ in calcium ion concentration and litter size. Anim Genet 2019; 50:326-333. [PMID: 31058330 DOI: 10.1111/age.12788] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/12/2019] [Indexed: 12/31/2022]
Abstract
Embryonic survival rate, an important factor in the fecundity of sows, is affected by endometrium-secreting histotroph. A higher concentration of calcium ion has been observed in the uterus of highly prolific Erhualian sows (EH) compared with those of less prolific (EL) sows. This suggests that EH sows have better establishment and maintenance of pregnancies, thus increasing embryonic survival rate during the peri-implantation period. To understand the mechanisms of how the endometrium-secreting histotroph affects embryonic survival rate during the Erhualian peri-implantation period, the expression patterns of endometrial mRNA in the EH and EL sows on day 12 of gestation were analyzed using RNA sequencing technology. A total of 164 differentially expressed genes (DEGs) were identified (Padj < 0.05, |log2 (FC)| ≥ 1), including 46 upregulated and 118 downregulated genes in EH compared to EL. Gene Ontology enrichment indicated that a subset of DEGs was involved in calcium ion binding and cell adhesion. Solute carrier family 8 member A3 and solute carrier family 24 member 4, identified as upregulated genes (Padj < 0.05) in EH, were considered key candidate genes expressed in the endometrium affecting embryonic survival rate during the peri-implantation period. The results improve understanding of the genetic mechanism underlying the variation in litter size of Erhualian pigs during the peri-implantation period.
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Affiliation(s)
- X Ma
- Institute of Swine Science, Nanjing Agricultural University, Nanjing, 210095, China
| | - P Li
- Institute of Swine Science, Nanjing Agricultural University, Nanjing, 210095, China
| | - Q Zhang
- Institute of Swine Science, Nanjing Agricultural University, Nanjing, 210095, China
| | - L He
- Institute of Swine Science, Nanjing Agricultural University, Nanjing, 210095, China
| | - G Su
- Department of Molecular Biology and Genetics, Center for Quantitative Genetics and Genomics, Aarhus University, Tjele, 8830, Denmark
| | - Y Huang
- Changzhou Jiaoxi Cooperatives of Erhualian Pigs, Changzhou, 213116, China
| | - Z Lu
- Changshu Animal Husbandry and Veterinary Station, Suzhou, 215500, China
| | - W Hu
- Changshu Animal Husbandry and Veterinary Station, Suzhou, 215500, China
| | - H Ding
- Changshu Agriculture Committee, Suzhou, 215500, China
| | - R Huang
- Institute of Swine Science, Nanjing Agricultural University, Nanjing, 210095, China
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20
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Chen Z, Zhou Y, Luo R, Liu K, Chen Z. Trophinin-associated protein expression is an independent prognostic biomarker in lung adenocarcinoma. J Thorac Dis 2019; 11:2043-2050. [PMID: 31285897 DOI: 10.21037/jtd.2019.04.86] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Background Lung cancer is the leading cause of cancer-related deaths worldwide, with lung adenocarcinoma (LAC) representing the most common subtype. Trophinin-associated protein (TROAP) is a cytoplasmic protein first identified to mediate the process of embryo transplantation, which has been recently found to be involved in microtubule regulation. However, limited information about the role of TROAP in LAC is available. Methods We evaluated the relationship of TROAP expression in LAC tissues with clinical pathologic parameters and the survival time in LAC patients based on a statistical analysis of The Cancer Genome Atlas (TCGA) lung cancer data (N=528). Differences in survival between high and low expression groups (median expression cutoff) from the Cox univariate/multivariate regression analysis were then compared. Results According to the Chi-square tests, we found high TROAP expression correlated with younger age (≤60) (P=0.047), male sex (P<0.005), an earlier T-stage (P=0.011), N-stage (P=0.017), M-stage (P=0.022), TNM (P=0.007), and a longer smoking history (>30 pack-year) (P<0.001). A Kaplan-Meier analysis demonstrated that high TROAP expression may correspond with poor overall survival of LAC patients in T3 stage (P=0.0013), N0 stage (P=0.014), and M0 stage (P=0.0023). Multivariate analysis confirmed that TROAP expression was related to overall survival in LAC patients independently [hazard ratio (HR): 1.784, 95% confidence interval (CI): 1.072-2.968, P=0.026]. Conclusions Our results suggested that TROAP is an independent prognostic biomarker of poor survival in LAC.
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Affiliation(s)
- Zhao Chen
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China
| | - Yuhan Zhou
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China
| | - Raojun Luo
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China
| | - Kai Liu
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China
| | - Zhoumiao Chen
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China
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21
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Bremer S, Brittebo E, Dencker L, Knudsen LE, Mathisien L, Olovsson M, Pazos P, Pellizzer C, Paulesu LR, Schaefer W, Schwarz M, Staud F, Stavreus-Evers A, Vähänkangas K. In Vitro Tests for Detecting Chemicals Affecting the Embryo Implantation Process. Altern Lab Anim 2019; 35:421-39. [PMID: 17850188 DOI: 10.1177/026119290703500407] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Susanne Bremer
- ECVAM, Institute for Health and Consumer Protection, European Commission Joint Research Centre, Ispra, Italy.
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22
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Hu H, Xu L, Chen Y, Luo SJ, Wu YZ, Xu SH, Liu MT, Lin F, Mei Y, Yang Q, Qiang YY, Lin YW, Deng YJ, Lin T, Sha YQ, Huang BJ, Zhang SJ. The Upregulation of Trophinin-Associated Protein (TROAP) Predicts a Poor Prognosis in Hepatocellular Carcinoma. J Cancer 2019; 10:957-967. [PMID: 30854102 PMCID: PMC6400818 DOI: 10.7150/jca.26666] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2018] [Accepted: 01/04/2019] [Indexed: 12/12/2022] Open
Abstract
Purpose: Trophinin-associated protein (TROAP) is a cytoplasmic protein that plays a significant role in the processes of embryo transplantation and microtubule regulation. However, the relevant survival analysis and cancer progression analysis have not yet been reported. Methods: Eighteen matched pairs of tumor and adjacent non-tumor samples were evaluated to detect the TROAP mRNA level. Immunohistochemistry (IHC) was used to evaluate the TROAP expression in 108 hepatocellular carcinoma patients who underwent surgical resection. Meanwhile, data from the TCGA database was statistically evaluated. Results: In the present study, we detected a significant increase in the TROAP mRNA level in tumor tissues when compared with adjacent non-tumor tissues. Moreover, the upregulation of TROAP was associated with increased serum AFP and GGT; the greater the tumor number was, the larger the tumor size, differentiation grade, and cancer embolus in clinical analysis. In HCC patients, elevated TROAP expression in the primary tumor was positively related to clinical severity, such as poor overall survival and disease-free survival. In addition, both univariate and multivariate survival analysis validated that TROAP expression was a promising independent risk factor for overall survival and disease-free survival in HCC patients. Furthermore, the results derived from the analysis of data from the TCGA database were consistent with previous results. Altogether, our results show that TROAP is a novel crucial regulator of HCC progression and is a potential therapeutic biomarker for HCC patients. Conclusions: Elevated TROAP expression predicted a poor prognosis, and TROAP may serve as a potential biomarker for application in oncotherapy.
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Affiliation(s)
- Hao Hu
- Department of Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, P. R. China
| | - Liang Xu
- State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P. R. China
| | - Yan Chen
- Department of Chinese Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, Guangdong, P. R. China
| | - Shao-Ju Luo
- Department of Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, P. R. China
| | - Ying-Zi Wu
- Department of Chinese Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, Guangdong, P. R. China
| | - Shi-Hua Xu
- Department of Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, P. R. China
| | - Meng-Ting Liu
- Department of Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, P. R. China
| | - Fen Lin
- State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P. R. China
| | - Yan Mei
- State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P. R. China
| | - Qin Yang
- State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P. R. China
| | - Yuan-Yuan Qiang
- State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P. R. China
| | - You-Wu Lin
- Department of Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, P. R. China
| | - Yuan-Jiang Deng
- Department of Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, P. R. China
| | - Tong Lin
- Department of Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, P. R. China
| | - Yong-Qiang Sha
- Department of Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, P. R. China
| | - Bi-Jun Huang
- State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P. R. China
| | - Shi-Jun Zhang
- Department of Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, P. R. China
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23
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Jiao Y, Li Y, Lu Z, Liu Y. High Trophinin-Associated Protein Expression Is an Independent Predictor of Poor Survival in Liver Cancer. Dig Dis Sci 2019; 64:137-143. [PMID: 30284652 DOI: 10.1007/s10620-018-5315-x] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Accepted: 09/29/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Trophinin-associated protein (TROAP) is a cytoplasmic protein that functions as an adhesion molecule in processes such as embryo implantation, spindle formation, and cancer. OBJECTIVE To evaluate the relationship of TROAP expression in hepatocellular carcinoma (HCC) tissue with clinicopathologic parameters and survival time in liver cancer patients based on an analysis of The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) data. METHODS RNA-sequencing (RNA-Seq) expression data and clinical information were downloaded for the TCGA-LIHC cohort. Associations between TROAP expression in HCC tissues and clinical parameters were evaluated by Chi-square tests. Differences in survival between high and low expression groups (median expression cutoff) from Cox regression analysis were compared, and P values were calculated by a log-rank test. Kaplan-Meier curves were compared with the log-rank test. RESULTS Analysis of RNA-Seq gene expression data for 373 patients with primary tumors revealed overexpression of TROAP in liver cancer. High TROAP expression was associated with survival status (P = 0.015), T stage (P = 0.049), clinical stage (P = 0.048), and gender (P = 0.033). Patients with high TROAP-expressing liver cancers had a shorter median overall survival of 3.83 years compared with 5.80 years for patients with low TROAP-expressing liver cancers (P = 0.00422). Multivariate analysis identified TROAP expression as an independent prognostic variable for overall survival in liver cancer patients. CONCLUSION TROAP expression is an independent predictor of poor survival in liver cancer.
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Affiliation(s)
- Yan Jiao
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, 130021, Jilin, People's Republic of China
| | - Yanqing Li
- Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, Jilin, People's Republic of China
| | - Zhengyang Lu
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, 130041, Jilin, People's Republic of China
| | - Yahui Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, 130021, Jilin, People's Republic of China.
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24
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Yoshinaga K. A historical review of blastocyst implantation research. Biol Reprod 2018; 99:175-195. [PMID: 30010858 PMCID: PMC6279068 DOI: 10.1093/biolre/ioy093] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 04/17/2018] [Accepted: 04/23/2018] [Indexed: 02/07/2023] Open
Abstract
Research development on blastocyst implantation was reviewed in three sections: primate implantation, ungulate farm animal implantation, and the general process of blastocyst implantation in small rodents. Future research directions of this area are suggested.
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Affiliation(s)
- Koji Yoshinaga
- Fertility and Infertility Branch, Division of Extramural Research, NICHD, NIH,
Bethesda, Maryland, USA
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25
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Jing K, Mao Q, Ma P. Decreased expression of TROAP suppresses cellular proliferation, migration and invasion in gastric cancer. Mol Med Rep 2018; 18:3020-3026. [PMID: 29956806 DOI: 10.3892/mmr.2018.9230] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Accepted: 11/11/2017] [Indexed: 11/06/2022] Open
Abstract
Trophinin associated protein (TROAP) is a cytoplasmic protein required for spindle assembly and cell invasion; however, its biological function in cancer remains to be elucidated. In the present study, by analyzing three independent datasets from the Oncomine database, it was identified that TROAP mRNA expression was upregulated in gastric cancer (GC) tissues compared with normal counterparts. Furthermore, elevated expression of TROAP was associated with poor survival in patients with GC, as predicted using Kaplan‑Meier analysis. TROAP was knocked down to verify its functional role in gastric cancer cell lines, SGC‑7901 and MGC80‑3. MTT assay was used to analyze cell proliferation. Cell cycle progression, and migration and invasion were determined using flow cytometry and Transwell assay, respectively. In vitro experiments demonstrated that knockdown of TROAP significantly suppressed cell proliferation, G1 to S cell cycle transition, and the migration and invasion ability of GC cells. The results of the present study suggest that TROAP is overexpressed in GC and serves an oncogenic role in gastric cancer by affecting cell proliferation and invasion.
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Affiliation(s)
- Ke Jing
- Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Qinsheng Mao
- Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Peng Ma
- Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
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26
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Ye X, Lv H. MicroRNA-519d-3p inhibits cell proliferation and migration by targeting TROAP in colorectal cancer. Biomed Pharmacother 2018; 105:879-886. [PMID: 30021381 DOI: 10.1016/j.biopha.2018.04.114] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Revised: 04/09/2018] [Accepted: 04/16/2018] [Indexed: 02/06/2023] Open
Abstract
Increasing evidence suggests that miR-519d-3p functions as tumor suppressor in several tumors, including breast cancer. However, its biological role in the development of colorectal cancer (CRC) still remains unclear. In this study, we found that miR-519d-3p expression level was remarkably down-regulated in CRC tissues samples and cell lines when compared to adjacent normal tissues and cell line by using qRT-PCR detection. Lower miR-519d-3p expression was significantly correlated with TNM stage, tumor size and lymph node metastasis. CRC patients with high level of miR-519d-3p had higher five-year survival rate than those with low expression of miR-519d-3p (p = 0.01178) using Kaplan-Meier analysis. Moreover, multivariate analysis suggested that miR-519d-3p expression might be an independent prognostic indicator for the survival of CRC patients. The in vitro functional analysis, including MTT, flow cytometry and transwell assays indicated that miR-519d-3p overexpression significantly suppressed cell proliferation, migration and invasion, induced cell cycle G0/G1 phase arrest and cell apoptosis of CRC cells. Furthermore, bioinformatics and luciferase reporter assays verified that trophinin associated protein (TROAP) was a direct target of miR-519d-3p in CRC cells. Using Oncomine database analysis, TROAP was confirmed to be upregulated in human CRC tissues. In addition, we found knockdown of TROAP presented similar inhibitory effects of miR-519d-3p overexpression in CRC cell function. In conclusion, miR-519d-3p might be a promising therapeutic strategy against human CRC by directly targeting TROAP.
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Affiliation(s)
- Xiaoyong Ye
- Department of Forensic Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Huizeng Lv
- Department of Forensic Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
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27
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28
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Lian Y, Fan W, Huang Y, Wang H, Wang J, Zhou L, Wu X, Deng M, Huang Y. Downregulated Trophinin-Associated Protein Plays a Critical Role in Human Hepatocellular Carcinoma Through Upregulation of Tumor Cell Growth and Migration. Oncol Res 2017; 26:691-701. [PMID: 29117881 PMCID: PMC7844635 DOI: 10.3727/096504017x15101398724809] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Trophinin-associated protein (TROAP) was a protein first identified to mediate the process of embryo transplantation and later found to be involved in microtubule regulation. However, little is known about the role of TROAP in hepatocellular carcinoma (HCC). In the present study, we reported that both TROAP mRNA and protein expressions were downregulated in human HCC samples as well as cell lines. A high level of TROAP was associated with small tumor size (p < 0.05), minor tumor nodules (p < 0.01), and mild vein invasion (p < 0.05). We further constructed in vitro TROAP depletion and overexpression HCC cell models. TROAP depletion significantly enhanced the proliferation and colony formation abilities, whereas TROAP overexpression had an inhibitory effect on the growth of HCC cells. The G1/S phase arrest by TROAP overexpression correlated with increased cell cycle inhibitors p21 and p27, and declined cell cycle promoting kinase complex CDK6/cyclin D1. Depressed TROAP expression enhanced the migration ability, while the opposite influence was observed in TROAP-overexpressed HCC cells. Taken together, these results indicate that TROAP suppresses cellular growth and migration in HCC. This discovery will further our understanding of the pathogenic mechanisms of human HCC.
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Affiliation(s)
- Yifan Lian
- Guangdong Province Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China
| | - Weiming Fan
- Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China
| | - Yanlin Huang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China
| | - Hongbo Wang
- Guangdong Province Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China
| | - Jialiang Wang
- Guangdong Province Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China
| | - Liang Zhou
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China
| | - Xiaojuan Wu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China
| | - Meihai Deng
- Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China
| | - Yuehua Huang
- Guangdong Province Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China
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29
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Zal F, Khademi F, Taheri R, Mostafavi-Pour Z. Antioxidant ameliorating effects against H2O2-induced cytotoxicity in primary endometrial cells. Toxicol Mech Methods 2017; 28:122-129. [DOI: 10.1080/15376516.2017.1372540] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- F. Zal
- Biochemistry Department, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
- Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - F. Khademi
- Biochemistry Department, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
| | - R. Taheri
- Biochemistry Department, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Z. Mostafavi-Pour
- Biochemistry Department, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
- Recombinant Protein Lab, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
- Maternal-Fetal Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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Fox C, Morin S, Jeong JW, Scott RT, Lessey BA. Local and systemic factors and implantation: what is the evidence? Fertil Steril 2016; 105:873-84. [PMID: 26945096 PMCID: PMC4821679 DOI: 10.1016/j.fertnstert.2016.02.018] [Citation(s) in RCA: 103] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Revised: 02/08/2016] [Accepted: 02/10/2016] [Indexed: 01/06/2023]
Abstract
Significant progress has been made in the understanding of embryonic competence and endometrial receptivity since the inception of assisted reproductive technology. The endometrium is a highly dynamic tissue that plays a crucial role in the establishment and maintenance of normal pregnancy. In response to steroid sex hormones, the endometrium undergoes marked changes during the menstrual cycle that are critical for acceptance of the nascent embryo. There is also a wide body of literature on systemic factors that impact assisted reproductive technology outcomes. Patient prognosis is impacted by an array of factors that tip the scales in her favor or against success. Recognizing the local and systemic factors will allow clinicians to better understand and optimize the maternal environment at the time of implantation. This review will address the current literature on endometrial and systemic factors related to impaired implantation and highlight recent advances in this area of reproductive medicine.
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Affiliation(s)
- Chelsea Fox
- Department of Obstetrics and Gynecology, Greenville Health System, Greenville, South Carolina
| | - Scott Morin
- Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey; Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology, and Reproductive Sciences, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey
| | - Jae-Wook Jeong
- Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, Michigan
| | - Richard T Scott
- Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey; Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology, and Reproductive Sciences, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey
| | - Bruce A Lessey
- Department of Obstetrics and Gynecology, Greenville Health System, Greenville, South Carolina.
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Dolanbay EG, Yardimoglu M, Yalcinkaya E, Yazir Y, Aksoy A, Karaoz E, Caliskan E. Expression of trophinin and dipeptidyl peptidase IV in endometrial co-culture in the presence of an embryo: A comparative immunocytochemical study. Mol Med Rep 2016; 13:3961-8. [PMID: 27035766 DOI: 10.3892/mmr.2016.5020] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Accepted: 02/12/2016] [Indexed: 11/06/2022] Open
Abstract
Recurrent implantation failure leads to a reduced pregnancy rate. The expression patterns of trophinin and dipeptidyl peptidase IV (CD26) indicate the involvement of embryo implantation and early placental development. The purpose of the present study was to evaluate endometrial co‑culture cells in the presence of embryo with trophinin and CD26 immunofluorescence staining. Patients with recurrent implantation failure were enrolled in the present study. The patients were aged between 26 and 36 years. Co‑cultures were prepared from endometrial biopsies for each patient. Controlled ovarian hyperstimulation was performed on each of the patients. Certain embryos were maintained in a conventional culture environment (n=80), and others in an endometrial co‑culture environment (n=25). Following embryo transfer, the co‑culture cells were examined under an inverted wide‑field fluorescence microscope. The ratio of a successful pregnancy was 0.38 in the present study (n=5/13 pregnancies). The average age of the successful group (28±3.54 years) was younger compared with the unsuccessful (32.67±2.81) group (P≤0.05). The number of trophinin (+) endometrial cells in the presence of an embryo was significantly lower (P=0.046) in the successful group on the first day. No significant difference between the groups was observed in terms of the number of CD26 (+) cells on the first to the fourth days (P≤0.05). Trophinin and CD26 immunostaining is important in the early period of pregnancy, and it will be beneficial in terms of providing the deficit of conventional culture medium in performed studies with the endometrial co‑culture medium. The co‑culture may be important, particularly in the early period, in patients with recurrent implantation failure in terms of enabling a connection between the cells belonging to the endometrium and the embryo.
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Affiliation(s)
- Elif Gelenli Dolanbay
- Department of Histology and Embryology, Faculty of Medicine, Kocaeli University, Campus of Umuttepe, Kocaeli 41380, Turkey
| | - Melda Yardimoglu
- Department of Histology and Embryology, Faculty of Medicine, Kocaeli University, Campus of Umuttepe, Kocaeli 41380, Turkey
| | - Ender Yalcinkaya
- Training and Research Hospital, IVF Unit, Faculty of Medicine, Kocaeli University, Campus of Umuttepe, Kocaeli 41380, Turkey
| | - Yusufhan Yazir
- Department of Histology and Embryology, Faculty of Medicine, Kocaeli University, Campus of Umuttepe, Kocaeli 41380, Turkey
| | - Ayca Aksoy
- Center of Stem Cell and Gene Therapies Research and Practice, Kocaeli University, Campus of Umuttepe, Kocaeli 41380, Turkey
| | - Erdal Karaoz
- Center for Regenerative Medicine and Stem Cell Research and Manufacturing (LivMedCell), Liv Hospital, İstanbul 34340, Turkey
| | - Eray Caliskan
- Department of Obstetrics and Gynecology, Faculty of Medicine, Bahçeşehir University, İstanbul 34353, Turkey
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Guerenne L, Beurlet S, Said M, Gorombei P, Le Pogam C, Guidez F, de la Grange P, Omidvar N, Vanneaux V, Mills K, Mufti GJ, Sarda-Mantel L, Noguera ME, Pla M, Fenaux P, Padua RA, Chomienne C, Krief P. GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways. J Hematol Oncol 2016; 9:5. [PMID: 26817437 PMCID: PMC4728810 DOI: 10.1186/s13045-016-0235-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2015] [Accepted: 01/19/2016] [Indexed: 12/13/2022] Open
Abstract
Background In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS) patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. Methods We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS) and acute myeloid leukemia (AML) post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. Results Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. Conclusions These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study. Electronic supplementary material The online version of this article (doi:10.1186/s13045-016-0235-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Laura Guerenne
- Université Paris-Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Unité Mixte de Recherche (UMR-S) 1131, Paris, France. .,Institut National de la Santé et de la Recherche Médicale (INSERM) Unité (U) 1131, Paris, France.
| | - Stéphanie Beurlet
- Université Paris-Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Unité Mixte de Recherche (UMR-S) 1131, Paris, France. .,Institut National de la Santé et de la Recherche Médicale (INSERM) Unité (U) 1131, Paris, France.
| | - Mohamed Said
- Department of Haematological Medicine, King's College London and Kings College Hospital, London, UK.
| | - Petra Gorombei
- Université Paris-Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Unité Mixte de Recherche (UMR-S) 1131, Paris, France. .,Institut National de la Santé et de la Recherche Médicale (INSERM) Unité (U) 1131, Paris, France.
| | - Carole Le Pogam
- Université Paris-Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Unité Mixte de Recherche (UMR-S) 1131, Paris, France. .,Institut National de la Santé et de la Recherche Médicale (INSERM) Unité (U) 1131, Paris, France.
| | - Fabien Guidez
- Université Paris-Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Unité Mixte de Recherche (UMR-S) 1131, Paris, France. .,Institut National de la Santé et de la Recherche Médicale (INSERM) Unité (U) 1131, Paris, France.
| | - Pierre de la Grange
- GenoSplice technology, iPEPS-ICM, Hôpital de la Pitié Salpêtrière, Paris, France.
| | - Nader Omidvar
- Haematology Department, Cardiff University School of Medicine, Cardiff, UK.
| | - Valérie Vanneaux
- Assistance Publique-Hôpitaux de Paris (AP-HP), Unité de Thérapie Cellulaire, Hôpital Saint Louis, Paris, France.
| | - Ken Mills
- Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
| | - Ghulam J Mufti
- Department of Haematological Medicine, King's College London and Kings College Hospital, London, UK.
| | - Laure Sarda-Mantel
- Université Paris-Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie Hôpital Saint Louis, Paris, France. .,Assistance Publique-Hôpitaux de Paris (AP-HP), Service de Médecine Nucléaire, Hôpital Lariboisière, Paris, France.
| | - Maria Elena Noguera
- Assistance Publique-Hôpitaux de Paris (AP-HP), Laboratoire d'Hématologie, Hôpital Saint Louis, Paris, France.
| | - Marika Pla
- Université Paris-Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Unité Mixte de Recherche (UMR-S) 1131, Paris, France. .,Institut National de la Santé et de la Recherche Médicale (INSERM) Unité (U) 1131, Paris, France. .,Université Paris-Diderot, Sorbonne Paris Cité, Département d'Expérimentation Animale, Institut Universitaire d'Hématologie, Paris, France.
| | - Pierre Fenaux
- Université Paris-Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Unité Mixte de Recherche (UMR-S) 1131, Paris, France. .,Institut National de la Santé et de la Recherche Médicale (INSERM) Unité (U) 1131, Paris, France. .,Assistance Publique-Hôpitaux de Paris (AP-HP), Laboratoire d'Hématologie, Hôpital Saint Louis, Paris, France.
| | - Rose Ann Padua
- Université Paris-Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Unité Mixte de Recherche (UMR-S) 1131, Paris, France. .,Institut National de la Santé et de la Recherche Médicale (INSERM) Unité (U) 1131, Paris, France. .,Assistance Publique-Hôpitaux de Paris (AP-HP), Laboratoire d'Hématologie, Hôpital Saint Louis, Paris, France.
| | - Christine Chomienne
- Université Paris-Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Unité Mixte de Recherche (UMR-S) 1131, Paris, France. .,Institut National de la Santé et de la Recherche Médicale (INSERM) Unité (U) 1131, Paris, France. .,Assistance Publique-Hôpitaux de Paris (AP-HP), Laboratoire d'Hématologie, Hôpital Saint Louis, Paris, France.
| | - Patricia Krief
- Université Paris-Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Unité Mixte de Recherche (UMR-S) 1131, Paris, France. .,Institut National de la Santé et de la Recherche Médicale (INSERM) Unité (U) 1131, Paris, France.
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Kim SW, Yang HG, Kang MC, Lee S, Namkoong H, Lee SW, Sung YC. KIAA1114, a full-length protein encoded by the trophinin gene, is a novel surface marker for isolating tumor-initiating cells of multiple hepatocellular carcinoma subtypes. Oncotarget 2015; 5:1226-40. [PMID: 24713374 PMCID: PMC4012722 DOI: 10.18632/oncotarget.1677] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Identification of novel biomarkers for tumor-initiating cells (TICs) is of critical importance for developing diagnostic and therapeutic strategies against cancers. Here we identified the role of KIAA1114, a full-length translational product of the trophinin gene, as a distinctive marker for TICs in human liver cancer by developing a DNA vaccine-induced monoclonal antibody targeting the putative extracellular domain of KIAA1114. Compared with other established markers of liver TICs, KIAA1114 was unique in that its expression was detected in both alpha fetoprotein (AFP)-positive and AFP-negative hepatocellular carcinoma (HCC) cell lines with the expression levels of KIAA1114 being positively correlated to their tumorigenic potentials. Notably, KIAA1114 expression was strongly detected in primary hepatic tumor, but neither in the adjacent non-tumorous tissue from the same patient nor normal liver tissue. KIAA1114high cells isolated from HCC cell lines displayed TIC-like features with superior functional and phenotypic traits compared to their KIAA1114low counterparts, including tumorigenic abilities in xenotransplantation model, in vitro colony- and spheroid-forming capabilities, expression of stemness-associated genes, and migratory capacity. Our findings not only address the value of a novel antigen, KIAA1114, as a potential diagnostic factor of human liver cancer, but also as an independent biomarker for identifying TIC populations that could be broadly applied to the heterogeneous HCC subtypes.
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Affiliation(s)
- Sae Won Kim
- Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea
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Yoshinaga K. Progesterone and Its Downstream Molecules as Blastocyst Implantation Essential Factors. Am J Reprod Immunol 2014; 72:117-28. [DOI: 10.1111/aji.12253] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Accepted: 03/15/2014] [Indexed: 12/31/2022] Open
Affiliation(s)
- Koji Yoshinaga
- Fertility and Infertility Branch; Division of Extramural Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; DHHS; Bethesda MD USA
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Oviductal and endometrial mRNA expression of implantation candidate biomarkers during early pregnancy in rabbit. ZYGOTE 2013; 23:288-96. [DOI: 10.1017/s0967199413000555] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
SummaryPrenatal losses are a complex problem. Pregnancy requires orchestrated communication between the embryo and the uterus that includes secretions from the embryo to signal pregnancy recognition and secretion and remodelling from the uterine epithelium. Most of these losses are characterized by asynchronization between embryo and uterus. To better understand possible causes, an analysis was conducted of gene expression of a set of transcripts related to maternal recognition and establishment of rabbit pregnancy (uteroglobin,SCGB1A1; integrin α1,ITGA1; interferon-γ,IFNG; vascular endothelial growth factor,VEGF) in oviduct and uterine tissue at 16, 72 or 144 h post-ovulation and insemination. In the oviduct tissue, a significant decrease in the level ofSCGB1A1mRNA expression was observed from 144 h post-ovulation. In the case ofITGA1, the transcript abundance was initially lower, but mRNA expression increased significantly at 72 and 144 h post-ovulation. ForIFNG, a huge decrease was observed from 16 to 72 h post-ovulation. Finally, no significant differences were observed in theVEGFtranscript. For the endometrium, the results showed a significant decline in the level ofSCGB1A1mRNA expression from 16 to 144 h post-ovulation induction. The highest levels ofITGA1transcript were detected at 144 h, followed by the 16 h group and lower at 72 h post-ovulation. ForIFNGthere were no significant differences among post-ovulation induction times. Finally, it was possible to observe thatVEGFmRNA abundance was present at low levels at 16 h post-ovulation and remained low at 72 h, but increased at 144 h. The functional significance of these observations may provide new insights into the maternal role in prenatal losses.
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Takami H, Kanda M, Oya H, Hibino S, Sugimoto H, Suenaga M, Yamada S, Nishikawa Y, Asai M, Fujii T, Nomoto S, Kodera Y. Evaluation of MAGE-D4 expression in hepatocellular carcinoma in Japanese patients. J Surg Oncol 2013; 108:557-62. [PMID: 24068544 DOI: 10.1002/jso.23440] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2013] [Accepted: 08/28/2013] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND OBJECTIVES Though Melanoma-associated antigen (MAGE) family genes have received lots of attention as cancer-related genes and targets for immunotherapy, MAGE-D4 expression in hepatocellular carcinoma (HCC) has not yet been evaluated. METHODS MAGE-D4 mRNA expression was assayed in nine HCC cell lines and 94 HCC surgical specimens obtained from Japanese patients by quantitative real-time reverse transcription polymerase chain reaction, and the correlations between MAGE-D4 mRNA expression and clinicopathological factors were evaluated. The expression and distribution of MAGE-D4b protein were evaluated immunohistochemically. RESULTS MAGE-D4 mRNA was overexpressed in five of nine HCC cell lines and 34 of 94 primary HCCs (36.2%). Median overall survival (14.8 vs. 118 months, P < 0.001) and relapse-free survival (2.7 vs. 18.3 months, P < 0.001) were significantly shorter in patients with high than with low-moderate MAGE-D4 expression. Multivariate analysis for overall survival showed that MAGE-D4 overexpression was independently prognostic for survival (hazard ratio 2.88, P = 0.009) and significantly associated with high alpha-fetoprotein concentration (P < 0.001), poor tumor differentiation (P = 0.003) and vascular invasion (P = 0.021). MAGE-D4b protein expression patterns were consistent with those of MAGE-D4 mRNA. CONCLUSIONS Overexpression of MAGE-D4 may be a predictive marker of early recurrence and mortality in patients with HCC.
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Affiliation(s)
- Hideki Takami
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
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Check JH, Cohen R. The role of progesterone and the progesterone receptor in human reproduction and cancer. Expert Rev Endocrinol Metab 2013; 8:469-484. [PMID: 30754194 DOI: 10.1586/17446651.2013.827380] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Insufficient progesterone, effect possibly more on immune factors rather than adequate endometrial development, can be an easy remedial cause of infertility by simply supplementing the luteal phase with either vaginal or intramuscular or oral (dydrogesterone) progesterone. Progesterone will also help to reduce miscarriage rates when follicle maturing drugs are used for those with regular menses but follicular maturation defects, or women with recurrent miscarriages. One mechanism of action seems to be related to production of an immunomodulatory protein, the progesterone-induced blocking factor either in the cytoplasm or in the circulation. PIBF inhibits cytotoxicity of natural killer cells. Cancer cells may 'borrow' the same mechanism to escape NK cell immunosurveillance.
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Affiliation(s)
- Jerome H Check
- a Department of Obstetrics and Gynecology, Cooper Medical School of Rowan University, Division of Reproductive Endocrinology & Infertility, Camden, NJ, USA
| | - Rachael Cohen
- b Department of Obstetrics and Gynecology, Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA
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Magnusson M, Sierra MI, Sasidharan R, Prashad SL, Romero M, Saarikoski P, Van Handel B, Huang A, Li X, Mikkola HKA. Expansion on stromal cells preserves the undifferentiated state of human hematopoietic stem cells despite compromised reconstitution ability. PLoS One 2013; 8:e53912. [PMID: 23342037 PMCID: PMC3547050 DOI: 10.1371/journal.pone.0053912] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2012] [Accepted: 12/04/2012] [Indexed: 12/15/2022] Open
Abstract
Lack of HLA-matched hematopoietic stem cells (HSC) limits the number of patients with life-threatening blood disorders that can be treated by HSC transplantation. So far, insufficient understanding of the regulatory mechanisms governing human HSC has precluded the development of effective protocols for culturing HSC for therapeutic use and molecular studies. We defined a culture system using OP9M2 mesenchymal stem cell (MSC) stroma that protects human hematopoietic stem/progenitor cells (HSPC) from differentiation and apoptosis. In addition, it facilitates a dramatic expansion of multipotent progenitors that retain the immunophenotype (CD34+CD38-CD90+) characteristic of human HSPC and proliferative potential over several weeks in culture. In contrast, transplantable HSC could be maintained, but not significantly expanded, during 2-week culture. Temporal analysis of the transcriptome of the ex vivo expanded CD34+CD38-CD90+ cells documented remarkable stability of most transcriptional regulators known to govern the undifferentiated HSC state. Nevertheless, it revealed dynamic fluctuations in transcriptional programs that associate with HSC behavior and may compromise HSC function, such as dysregulation of PBX1 regulated genetic networks. This culture system serves now as a platform for modeling human multilineage hematopoietic stem/progenitor cell hierarchy and studying the complex regulation of HSC identity and function required for successful ex vivo expansion of transplantable HSC.
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Affiliation(s)
- Mattias Magnusson
- Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America
| | - Maria I. Sierra
- Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America
| | - Rajkumar Sasidharan
- Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America
| | - Sacha L. Prashad
- Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America
| | - Melissa Romero
- Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America
| | - Pamela Saarikoski
- Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America
| | - Ben Van Handel
- Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America
| | - Andy Huang
- Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America
| | - Xinmin Li
- Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, United States of America
| | - Hanna K. A. Mikkola
- Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America
- Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, California, United States of America
- Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California, United States of America
- Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, United States of America
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Zhang S, Lin H, Kong S, Wang S, Wang H, Wang H, Armant DR. Physiological and molecular determinants of embryo implantation. Mol Aspects Med 2013; 34:939-80. [PMID: 23290997 DOI: 10.1016/j.mam.2012.12.011] [Citation(s) in RCA: 386] [Impact Index Per Article: 32.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2012] [Revised: 12/25/2012] [Accepted: 12/26/2012] [Indexed: 01/19/2023]
Abstract
Embryo implantation involves the intimate interaction between an implantation-competent blastocyst and a receptive uterus, which occurs in a limited time period known as the window of implantation. Emerging evidence shows that defects originating during embryo implantation induce ripple effects with adverse consequences on later gestation events, highlighting the significance of this event for pregnancy success. Although a multitude of cellular events and molecular pathways involved in embryo-uterine crosstalk during implantation have been identified through gene expression studies and genetically engineered mouse models, a comprehensive understanding of the nature of embryo implantation is still missing. This review focuses on recent progress with particular attention to physiological and molecular determinants of blastocyst activation, uterine receptivity, blastocyst attachment and uterine decidualization. A better understanding of underlying mechanisms governing embryo implantation should generate new strategies to rectify implantation failure and improve pregnancy rates in women.
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Affiliation(s)
- Shuang Zhang
- State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China; Graduate School of the Chinese Academy of Sciences, Beijing 100039, PR China
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Park SK, Yoon J, Wang L, Shibata TK, Motamedchaboki K, Shim KJ, Chang MS, Lee SH, Tamura N, Hatakeyama S, Nadano D, Sugihara K, Fukuda MN. Enhancement of mouse sperm motility by trophinin-binding peptide. Reprod Biol Endocrinol 2012; 10. [PMID: 23194061 PMCID: PMC3551822 DOI: 10.1186/1477-7827-10-101] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Trophinin is an intrinsic membrane protein that forms a complex in the cytoplasm with bystin and tastin, linking it microtubule-associated motor dynein (ATPase) in some cell types. Previously, we found that human sperm tails contain trophinin, bystin and tastin proteins, and that trophinin-binding GWRQ (glycine, tryptophan, arginine, glutamine) peptide enhanced motility of human sperm. METHODS Immunohistochemistry was employed to determine trophinin protein in mouse spermatozoa from wild type mouse, by using spermatozoa from trophinin null mutant mice as a negative control. Multivalent 8-branched GWRQ (glycine, tryptophan, arginine, glutamine) peptide or GWRQ-MAPS, was chemically synthesized, purified by HPLC and its structure was confirmed by MALDI-TOF mass spectrometry. Effect of GWRQ-MAPS on mouse spermatozoa from wild type and trophinin null mutant was assessed by a computer-assisted semen analyzer (CASA). RESULTS Anti-trophinin antibody stained the principal (central) piece of the tail of wild type mouse sperm, whereas the antibody showed no staining on trophinin null sperm. Phage particles displaying GWRQ bound to the principal piece of sperm tail from wild type but not trophinin null mice. GWRQ-MAPS enhanced motility of spermatozoa from wild type but not trophinin null mice. CASA showed that GWRQ-MAPS enhanced both progressive motility and rapid motility in wild type mouse sperm. CONCLUSIONS Present study established the expression of trophinin in the mouse sperm tail and trophinin-dependent effect of GWRQ-MAPS on sperm motility. GWRQ causes a significant increase in sperm motility.
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Affiliation(s)
- Seong Kyu Park
- Tumor Microenvironment Program, Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Rd, La Jolla, CA 92037, USA
- Department of Prescriptionology, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea
| | - Jiwon Yoon
- Tumor Microenvironment Program, Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Rd, La Jolla, CA 92037, USA
- Department of Prescriptionology, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea
| | - Ling Wang
- Tumor Microenvironment Program, Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Rd, La Jolla, CA 92037, USA
| | - Toshiaki K Shibata
- Tumor Microenvironment Program, Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Rd, La Jolla, CA 92037, USA
- Department of Gynecology and Obstetrics, Hamamatsu University School of Medicine, Hamamatsu City, Shizuoka, 431-3192, Japan
| | - Khatereh Motamedchaboki
- Tumor Microenvironment Program, Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Rd, La Jolla, CA 92037, USA
| | - Kyung Jun Shim
- Tumor Microenvironment Program, Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Rd, La Jolla, CA 92037, USA
- Department of Prescriptionology, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea
| | - Mun Seog Chang
- Department of Prescriptionology, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea
| | - Seung Ho Lee
- Tumor Microenvironment Program, Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Rd, La Jolla, CA 92037, USA
| | - Naoaki Tamura
- Tumor Microenvironment Program, Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Rd, La Jolla, CA 92037, USA
- Department of Gynecology and Obstetrics, Hamamatsu University School of Medicine, Hamamatsu City, Shizuoka, 431-3192, Japan
| | - Shingo Hatakeyama
- Tumor Microenvironment Program, Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Rd, La Jolla, CA 92037, USA
- Department of Urology, Hirosaki University School of Medicine, Hirosaki, Aomori, 036-8562, Japan
| | - Daita Nadano
- Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya, 464-8601, Japan
| | - Kazuhiro Sugihara
- Department of Gynecology and Obstetrics, Hamamatsu University School of Medicine, Hamamatsu City, Shizuoka, 431-3192, Japan
| | - Michiko N Fukuda
- Tumor Microenvironment Program, Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Rd, La Jolla, CA 92037, USA
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41
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Kaneko Y, Murphy CR, Day ML. Extracellular matrix proteins secreted from both the endometrium and the embryo are required for attachment: a study using a co-culture model of rat blastocysts and Ishikawa cells. J Morphol 2012; 274:63-72. [PMID: 22972746 DOI: 10.1002/jmor.20076] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2012] [Revised: 06/25/2012] [Accepted: 08/09/2012] [Indexed: 11/08/2022]
Abstract
Integrins are expressed in a highly regulated manner at the maternal-fetal interface during implantation. However, the significance of extracellular matrix (ECM) ligands during the integrin-mediated embryo attachment to the endometrium is not fully understood. Thus, the distribution of fibronectin in the rat uterus and blastocyst was studied at the time of implantation. Fibronectin was absent in the uterine luminal epithelial cells but was intensely expressed in the trophoblast cells and the inner cell mass suggesting that fibronectin secreted from the blastocyst may be a possible bridging ligand for the integrins expressed at the maternal-fetal interface. An Arg-Gly-Asp (RGD) peptide was used to block the RGD recognition sites on integrins, and the effect on rat blastocyst attachment to Ishikawa cells was examined. There was a significant reduction in blastocyst attachment when either the blastocysts or the Ishikawa cells were pre-incubated with the RGD-blocking peptide. Thus, successful attachment of the embryo to the endometrium requires the interaction of integrins on both the endometrium and the blastocyst with the RGD sequence of ECM ligands, such as fibronectin. Pre-treatment of both blastocysts and Ishikawa cells with the RGD peptide also inhibited blastocyst attachment, but not completely, suggesting that ECM bridging ligands that do not contain the RGD sequence are also involved in embryo attachment.
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Affiliation(s)
- Yui Kaneko
- Discipline of Anatomy and Histology, School of Medical Sciences and The Bosch Institute, The University of Sydney, Sydney, New South Wales 2006, Australia.
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42
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Jiang K, Toedt G, Montenegro Gouveia S, Davey NE, Hua S, van der Vaart B, Grigoriev I, Larsen J, Pedersen LB, Bezstarosti K, Lince-Faria M, Demmers J, Steinmetz MO, Gibson TJ, Akhmanova A. A Proteome-wide screen for mammalian SxIP motif-containing microtubule plus-end tracking proteins. Curr Biol 2012; 22:1800-7. [PMID: 22885064 DOI: 10.1016/j.cub.2012.07.047] [Citation(s) in RCA: 167] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2012] [Revised: 07/10/2012] [Accepted: 07/23/2012] [Indexed: 11/26/2022]
Abstract
Microtubule plus-end tracking proteins (+TIPs) are structurally and functionally diverse factors that accumulate at the growing microtubule plus-ends, connect them to various cellular structures, and control microtubule dynamics [1, 2]. EB1 and its homologs are +TIPs that can autonomously recognize growing microtubule ends and recruit to them a variety of other proteins. Numerous +TIPs bind to end binding (EB) proteins through natively unstructured basic and serine-rich polypeptide regions containing a core SxIP motif (serine-any amino acid-isoleucine-proline) [3]. The SxIP consensus sequence is short, and the surrounding sequences show high variability, raising the possibility that undiscovered SxIP containing +TIPs are encoded in mammalian genomes. Here, we performed a proteome-wide search for mammalian SxIP-containing +TIPs by combining biochemical and bioinformatics approaches. We have identified a set of previously uncharacterized EB partners that have the capacity to accumulate at the growing microtubule ends, including protein kinases, a small GTPase, centriole-, membrane-, and actin-associated proteins. We show that one of the newly identified +TIPs, CEP104, interacts with CP110 and CEP97 at the centriole and is required for ciliogenesis. Our study reveals the complexity of the mammalian +TIP interactome and provides a basis for investigating the molecular crosstalk between microtubule ends and other cellular structures.
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Affiliation(s)
- Kai Jiang
- Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands
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Huang Q, Huang HQ. Alterations of protein profile in zebrafish liver cells exposed to methyl parathion: a membrane proteomics approach. CHEMOSPHERE 2012; 87:68-76. [PMID: 22182705 DOI: 10.1016/j.chemosphere.2011.11.061] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2011] [Revised: 11/13/2011] [Accepted: 11/19/2011] [Indexed: 05/31/2023]
Abstract
Methyl parathion (MP) is an extensively used organophosphorus pesticide, which has been associated with a wide spectrum of toxic effects on environmental organisms. The aim of this study is to investigate the alterations of membrane protein profiles in zebrafish liver (ZFL) cell line exposed to MP for 24 h using proteomic approaches. Two-dimensional gel electrophoresis revealed a total of 13 protein spots, whose expression levels were significantly altered by MP. These differential proteins were subjected to matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry analysis, and nine proteins were identified to be membrane proteins, among which seven were up-regulated, while two were down-regulated. In addition, the mRNA levels corresponding to these differential membrane proteins were further analyzed by quantitative real-time PCR. And the differential expression of arginase-2 was specially validated via Western blotting. Regarding the physiological functions, these proteins are involved in molecular chaperon, cytoskeleton system, cell metabolism, signal transduction, transport and hormone receptor respectively, suggesting the complexity of MP-mediated toxicity to ZFL cell. These data could provide useful insights for better understanding the hepatotoxic mechanisms of MP and develop novel protein biomarkers for effectively monitoring MP contamination level in aquatic environment.
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Affiliation(s)
- Qingyu Huang
- State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China
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Abstract
OBJECTIVE To provide a focused review of the scientific literature pertaining to endometrial receptivity. DESIGN Review of the literature and appraisal of relevant articles. SETTING Academic teaching hospital. PATIENT(S) Women with infertility. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Critical review of the literature. RESULT(S) Although a consensus has been achieved regarding the existence of a temporally defined period during which embryo attachment and invasion can occur (called the "window of implantation"), reliable methods to assess "receptivity" have not been established or adequately validated. In women with certain gynecologic disorders, including endometriosis, tubal disease, and polycystic ovary syndrome, endometrial receptivity seems to be compromised, leading to infertility and pregnancy loss. The establishment of reliable biomarkers for the detection of defects in endometrial receptivity has been a long-sought goal that remains an elusive target. The validation of endometrial biomarkers will require properly designed and implemented studies based on the recognition that endometrial receptivity defects are not equally distributed in women with endometriosis or these other conditions. CONCLUSION(S) Rapidly advancing technologies are bringing new biomarkers to the clinical arena that promise to further reveal the complexities of the implantation process.
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Tamura N, Sugihara K, Akama TO, Fukuda MN. Trophinin-mediated cell adhesion induces apoptosis of human endometrial epithelial cells through PKC-δ. Cell Cycle 2011; 10:135-43. [PMID: 21191175 DOI: 10.4161/cc.10.1.14448] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Trophinin is an intrinsic membrane protein expressed in trophectoderm cells of embryos and in uterine epithelial cells. Trophinin potentially mediates apical cell adhesion at human embryo implantation sites through trophinin-trophinin binding in these two cell types. Trophinin-mediated cell adhesion activates trophectoderm cells for invasion, whereas the effect of adhesion on maternal side is not known. We show that addition of GWRQ peptide, a previously established peptide that mimics trophinin-mediated cell adhesion, to human endometrial epithelial cells expressing trophinin induces their apoptosis. FAS involvement was excluded, as GWRQ did not bind to FAS, and FAS knockdown did not alter GWRQ-induced apoptosis. Immunoblotting analyses of protein kinases revealed an elevation of PKC-d protein in GWRQ-bound endometrial epithelial cells. In the absence of GWRQ, PKC-d associated with trophinin and remained cytoplasmic, but after GWRQ binding to the trophinin extracellular domain, PKC-d became tyrosine phosphorylated, dissociated from trophinin, and entered the nucleus. In PKC-d knockdown endometrial cells, GWRQ did not induce apoptosis.
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Affiliation(s)
- Naoaki Tamura
- Tumor Microenvironment Program, Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA
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46
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Fujii H, Fujiwara H, Horie A, Sato Y, Konishi I. Ephrin A1 induces intercellular dissociation in Ishikawa cells: possible implication of the Eph-ephrin A system in human embryo implantation. Hum Reprod 2010; 26:299-306. [DOI: 10.1093/humrep/deq340] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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47
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Chen W, Cao G, Zhang SL. Is CD146 pivotal in neoplasm invasion and blastocyst embedding? Med Hypotheses 2010; 76:378-80. [PMID: 21095067 DOI: 10.1016/j.mehy.2010.10.045] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2010] [Revised: 10/25/2010] [Accepted: 10/28/2010] [Indexed: 12/31/2022]
Abstract
Blastocyst embedding is very similar to neoplasm invasion. Blastocyst embedding is seeding the young plant of life, while neoplasm invasion is knocking at the door of death. Overexpression of melanoma cell adhesion molecule (CD146 or MCAM), a novel member of the immunoglobulingene superfamily, promotes invasion, metastasis, growth and survival of malignant cells, and implantation of blastocyst embedding in placenta. We hypothesize that CD146 may be a key gene both in neoplasm invasion and blastocyst embedding because of its ability in regulating cell invasion. The regulation of CD146 expression may be a control switch in the progress of the neoplasm invasion and blastocyst embedding. If the hypothesis is correct, the inhibition of CD146 can be used to prevent and/or treat tumor invasion. Current treatment modalities of tumor invasion include different therapies: surgical resection, radiotherapy, chemotherapy, etc. These treatments are all non-specific to tumor cells. If further studies proof our hypothesis, CD146 may be a candidate target gene in gene therapy of tumor invasion and in regulation of blastocyst embedding.
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Affiliation(s)
- Wei Chen
- Department of Stomatology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, PR China.
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48
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Yang L, Zhang X, Chen J, Wang Q, Wang L, Jiang Y, Pan Y. ReCGiP, a database of reproduction candidate genes in pigs based on bibliomics. Reprod Biol Endocrinol 2010; 8:96. [PMID: 20707928 PMCID: PMC3224910 DOI: 10.1186/1477-7827-8-96] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2010] [Accepted: 08/14/2010] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Reproduction in pigs is one of the most economically important traits. To improve the reproductive performances, numerous studies have focused on the identification of candidate genes. However, it is hard for one to read all literatures thoroughly to get information. So we have developed a database providing candidate genes for reproductive researches in pig by mining and processing existing biological literatures in human and pigs, named as ReCGiP. DESCRIPTION Based on text-mining and comparative genomics, ReCGiP presents diverse information of reproduction-relevant genes in human and pig. The genes were sorted by the degree of relevance with the reproduction topics and were visualized in a gene's co-occurrence network where two genes were connected if they were co-cited in a PubMed abstract. The 'hub' genes which had more 'neighbors' were thought to be have more important functions and could be identified by the user in their web browser. In addition, ReCGiP provided integrated GO annotation, OMIM and biological pathway information collected from the Internet. Both pig and human gene information can be found in the database, which is now available. CONCLUSIONS ReCGiP is a unique database providing information on reproduction related genes for pig. It can be used in the area of the molecular genetics, the genetic linkage map, and the breeding of the pig and other livestock. Moreover, it can be used as a reference for human reproduction research.
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Affiliation(s)
- Lun Yang
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China
- Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Xiangzhe Zhang
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China
- Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai, 200240, China
| | - Jian Chen
- Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Qishan Wang
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Lishan Wang
- Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Yue Jiang
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Yuchun Pan
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China
- Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai, 200240, China
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49
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Singh H, Aplin JD. Adhesion molecules in endometrial epithelium: tissue integrity and embryo implantation. J Anat 2009; 215:3-13. [PMID: 19453302 PMCID: PMC2714633 DOI: 10.1111/j.1469-7580.2008.01034.x] [Citation(s) in RCA: 114] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/14/2008] [Indexed: 12/16/2022] Open
Abstract
Cell adhesion in endometrial epithelium is regulated to maintain the continuity and protectiveness of the luminal covering cell layer while permitting interstitial implantation of the embryo during a restricted period of about 4 days. Many apparently normal embryos fail to implant, and epithelial-embryo adhesion remains a poorly understood phenomenon. After menstruation, epithelial regeneration occurs by epiboly from the basal residues of glands, an activity that requires migration on extracellular matrix as well as cell-cell cohesion. Here we review current knowledge of adhesion molecules in the epithelium.
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Affiliation(s)
- Harmeet Singh
- Maternal and Fetal Health Research Group, University of Manchester, Manchester, UK
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50
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Sasaki A, Hinck L, Watanabe K. RumMAGE-D the Members: Structure and Function of a New Adaptor Family of MAGE-D Proteins. J Recept Signal Transduct Res 2008; 25:181-98. [PMID: 16194933 DOI: 10.1080/10799890500210511] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
MAGE genes were first described as cancer-testis antigens, which are silenced in normal adult tissues but aberrantly expressed in tumor cells. The short peptides, derived from the degradation of MAGE transcripts, are the source of antigens that cause tumor rejection reactions when presented in the context of major histocompatibility complex. The recent discovery of a subset of genes that contain the structurally conserved MAGE homology domain (MHD) has accelerated the investigation into the normal function of MAGE genes. This new type of MAGE gene is normally expressed in embryonal and adult tissue, especially the brain. MAGE-D1, also known as NRAGE or Dlxin-1, functions as an adaptor protein that mediates multiple signaling pathways, including NGFR (p75NTR) and UNC5H1-induced apoptosis and Dlx/Msx-mediated transcription. Loss of a different MAGE family member, Necdin, which works as a cell cycle regulator, may play a role in the pathogenesis of Prader-Willi syndrome, a neurobehavioral disorder. In this article, the authors discuss recent findings concerning the structure and function of new MAGE genes, primarily focusing on MAGE-D1. Because some MAGE-D subfamily proteins share significant homology within the MHD, these recent discoveries on MAGE-D1 may give insight into the function of other MAGE-D proteins.
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Affiliation(s)
- Aya Sasaki
- Division of the Clinical Pathology, Sapporo Medical University Hospital, Hokkaido, Japan
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