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Wang X, Li H, Xu A, Peng J, Wu Y, Liu Y, Zhang J, Cai C, Ma S, Zhang K. Inhibition of the long non-coding RNA MALAT1 downregulates MAP2K1, suppressing the progression of hypopharyngeal squamous cell carcinoma. BIOMOLECULES & BIOMEDICINE 2025; 25:1023-1037. [PMID: 39319867 PMCID: PMC11984367 DOI: 10.17305/bb.2024.11151] [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: 08/16/2024] [Revised: 09/19/2024] [Accepted: 09/19/2024] [Indexed: 09/26/2024]
Abstract
This study aimed to explore the role of long non-coding RNAs metastasis-associated lung adenocarcinoma transcript (lncRNA MALAT1), and its underlying mechanisms in hypopharyngeal squamous cell carcinoma (HSCC). Quantitative real-time PCR (qRT-PCR) was employed to measure lncRNA MALAT1 expression in HSCC and adjacent non-cancerous tissues, along with the expression of the downstream target mitogen-activated protein kinase kinase 1 (MAP2K1). The independent prognostic significance of lncRNA MALAT1 was assessed using Cox regression analysis. Potential downstream targets of MALAT1 were identified through parallel reaction monitoring (PRM) analysis and validated using the TCGA-HNSC database, Western blotting, and immunohistochemistry. CCK-8, flow cytometry, and Transwell assays were conducted to assess the effects of the lncRNA MALAT1/MAP2K1 axis on FaDu cells. Additionally, a nude mouse xenograft model was used to confirm the role of lncRNA MALAT1/MAP2K1 in tumor growth. LncRNA MALAT1 was significantly upregulated in HSCC tissues and closely associated with poor prognosis. Bioinformatics analysis, including PRM screening and TCGA-HNSC data, identified FERMT2, CSNK2A2, and MAP2K1 as potential downstream targets of MALAT1. Validation through qPCR, Western blotting, and immunohistochemistry confirmed MAP2K1 as a downstream target. In vitro and in vivo experiments demonstrated that inhibiting lncRNA MALAT1 suppressed cell proliferation, migration, and epithelial-to-mesenchymal transition (EMT) by downregulating MAP2K1 expression. Additionally, it induced apoptosis, affected the cell cycle, and inhibited tumor growth. Our study uniquely demonstrates that targeting MALAT1 significantly impedes HSCC progression by downregulating its novel downstream target, MAP2K1, offering new insights into potential therapeutic strategies.
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Affiliation(s)
- Xiaomin Wang
- Anhui Medical University, Hefei, China
- Department of Otolaryngology and Head and Neck surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Hui Li
- Anhui Medical University, Hefei, China
- Department of Otolaryngology and Head and Neck surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Aoxuan Xu
- Department of Otolaryngology and Head and Neck surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Jie Peng
- Department of Otolaryngology and Head and Neck surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Yanqing Wu
- Department of Otolaryngology and Head and Neck surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Yunfan Liu
- Department of Otolaryngology and Head and Neck surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Junjie Zhang
- Department of Otolaryngology and Head and Neck surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Changqi Cai
- Department of Otolaryngology and Head and Neck surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Shiyin Ma
- Department of Otolaryngology and Head and Neck surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Kai Zhang
- Anhui Medical University, Hefei, China
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China
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Wei X, Si A, Zhao S, Fu Y, Li J, Aishanjiang K, Ma Y, Yu C, Yu B, Cui C, Wang H, Kong X, Li S, Kong X, Tong Y, Wu H. CircUCK2(2,3) promotes cancer progression and enhances synergistic cytotoxicity of lenvatinib with EGFR inhibitors via activating CNIH4-TGFα-EGFR signaling. Cell Mol Biol Lett 2025; 30:15. [PMID: 39885395 PMCID: PMC11781035 DOI: 10.1186/s11658-025-00690-1] [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: 08/20/2024] [Accepted: 01/08/2025] [Indexed: 02/01/2025] Open
Abstract
BACKGROUND Circular (circ)RNAs have emerged as crucial contributors to cancer progression. Nonetheless, the expression regulation, biological functions, and underlying mechanisms of circRNAs in mediating hepatocellular carcinoma (HCC) progression remain insufficiently elucidated. METHODS We identified circUCK2(2,3) through circRNA sequencing, RT-PCR, and Sanger sequencing. CircUCK2(2,3) levels were measured in two independent HCC cohorts using quantitative real-time PCR (qRT-PCR). We explored the functions of circUCK2(2,3) using gain- and loss-of-function assays. Techniques such as RNA-sequencing, RNA immunoprecipitation (RIP), polysome fractionation, RNA pulldown, dual luciferase reporter assay, inhibitors of EGFR downstream signaling, CRISPR-Cas9, and medium transfer assays were employed to investigate the regulatory mechanisms and the protumoral activities of circUCK2(2,3). Additionally, in vitro cytotoxic assays and patient-derived xenograft (PDX) models assessed the effects of circUCK2(2,3) on the cytotoxic synergy of lenvatinib and EGFR inhibitors. RESULTS CircUCK2(2,3) is upregulated in HCC tissues and serves as an independent risk factor for poor recurrence-free survival. The expression of circUCK2(2,3) is independent on its host gene, UCK2, but is regulated by its upstream promoter and flanking inverted complementary sequences. Functionally, circUCK2(2,3) enhances HCC proliferation, migration, and invasion, both in vitro and in vivo. Mechanistically, by sponging miR-149-5p, circUCK2(2,3) increases CNIH4 levels, which in turn amplifies TGFα secretion, resulting in the activation of EGFR and downstream pAKT and pERK signaling pathways. Moreover, circUCK2(2,3) overexpression sensitizes HCC cells to EGFR inhibitors, and increases the synergistic cytotoxicity of combined lenvatinib and EGFR inhibitor treatment. CONCLUSIONS CircUCK2(2,3) regulates a novel oncogenic pathway, miR-149-5p-CNIH4-TGFα-EGFR, in HCC, presenting a viable therapeutic target and biomarker for the precision treatment of HCC.
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Affiliation(s)
- Xindong Wei
- Clinical Research Center, Jiading District Central Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, 201800, China
- Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, 201203, China
- Collaborative Research Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Anfeng Si
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210015, China
| | - Shuai Zhao
- Department of Transplantation, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Yi Fu
- Clinical Research Center, Jiading District Central Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, 201800, China
- Collaborative Research Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Jilei Li
- Clinical Research Center, Jiading District Central Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, 201800, China
- Collaborative Research Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Kedeerya Aishanjiang
- Clinical Research Center, Jiading District Central Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, 201800, China
- Department of Transplantation, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
- People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 831399, China
| | - Yujie Ma
- Clinical Research Center, Jiading District Central Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, 201800, China
- Collaborative Research Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Chang Yu
- Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, 201203, China
| | - Bo Yu
- School of Clinical Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Chunhong Cui
- Basic Medical College, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Hui Wang
- Basic Medical College, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Xianming Kong
- Collaborative Research Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Shibo Li
- Department of Infectious Disease, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, 316100, China.
| | - Xiaoni Kong
- Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, 201203, China.
| | - Ying Tong
- Department of Liver Surgery, School of Medicine, Renji Hospital, Shanghai JiaoTong University, Shanghai, 200003, China.
| | - Hailong Wu
- Clinical Research Center, Jiading District Central Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, 201800, China.
- Collaborative Research Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China.
- School of Pharmacy, Joint Innovation Laboratory for Cell Therapy Technology, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China.
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Wu H, Sun C, Cao W, Teng Q, Ma X, Schiöth HB, Dong R, Zhang Q, Kong B. Blockade of the lncRNA-PART1-PHB2 axis confers resistance to PARP inhibitor and promotes cellular senescence in ovarian cancer. Cancer Lett 2024; 602:217192. [PMID: 39181433 DOI: 10.1016/j.canlet.2024.217192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 08/09/2024] [Accepted: 08/14/2024] [Indexed: 08/27/2024]
Abstract
PARPi is currently the most important breakthrough in the treatment of ovarian cancer in decades, and it has been integrated into the initial maintenance therapy for ovarian cancer. However, the mechanism leading to PARPi resistance remains unelucidated. Our study aims to screen novel targets to better predict and reverse resistance to PARPi and explore the potential mechanism. Here, we conducted a comparative analysis of differentially expressed genes between platinum-sensitive and platinum-resistant groups within the TCGA ovarian cancer cohort. The analysis indicated that lncRNA PART1 was significantly highly expressed in platinum-sensitive patients compared to platinum-resistant individuals in TCGA-OV cohort and further validated in the GEO dataset and Qilu hospital cohort. Moreover, the upregulation of PART1 was positively correlated with a favorable prognosis in ovarian cancer. Furthermore, in vitro and in vivo experiments showed that inhibition of PART1 conferred resistance to both cisplatin and PARP inhibitor and promoted cellular senescence. Senescent cells are more resistant to chemotherapeutics. RNA antisense purification and RNA immunoprecipitation assays revealed an interaction between PART1 and PHB2, a crucial mitophagy receptor. Knockdown of PART1 could promote the degradation of PHB2, impairing mitophagy and leading to cellular senescence. Rescue assays indicated that overexpression of PHB2 remarkably diminished the resistance to PARPi and cellular senescence caused by PART1 knockdown. PDX models were utilized to further confirm the findings. Altogether, our study demonstrated that lncRNA PART1 has the potential to serve as a novel promising target to reverse resistance to PARPi and improve prognosis in ovarian cancer.
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Affiliation(s)
- Huan Wu
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong, 250012, PR China; Gynecology Oncology Key Laboratory, Qilu Hospital of Shandong University, Ji'nan, Shandong, 250012, PR China
| | - Chenggong Sun
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong, 250012, PR China; Gynecology Oncology Key Laboratory, Qilu Hospital of Shandong University, Ji'nan, Shandong, 250012, PR China
| | - Wenyu Cao
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong, 250012, PR China; Gynecology Oncology Key Laboratory, Qilu Hospital of Shandong University, Ji'nan, Shandong, 250012, PR China
| | - Qiuli Teng
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong, 250012, PR China; Gynecology Oncology Key Laboratory, Qilu Hospital of Shandong University, Ji'nan, Shandong, 250012, PR China
| | - Xinyue Ma
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong, 250012, PR China; Gynecology Oncology Key Laboratory, Qilu Hospital of Shandong University, Ji'nan, Shandong, 250012, PR China
| | - Helgi B Schiöth
- Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden
| | - Ruifen Dong
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong, 250012, PR China; Gynecology Oncology Key Laboratory, Qilu Hospital of Shandong University, Ji'nan, Shandong, 250012, PR China
| | - Qing Zhang
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong, 250012, PR China; Gynecology Oncology Key Laboratory, Qilu Hospital of Shandong University, Ji'nan, Shandong, 250012, PR China.
| | - Beihua Kong
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong, 250012, PR China; Gynecology Oncology Key Laboratory, Qilu Hospital of Shandong University, Ji'nan, Shandong, 250012, PR China.
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Zeng J, Feng Y, Lin L, Ye H, Shen H, Sun Y. Circ_0000069 promotes the development of hepatocellular carcinoma by regulating CCL25. BMC Cancer 2024; 24:827. [PMID: 38992592 PMCID: PMC11238365 DOI: 10.1186/s12885-024-12594-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Accepted: 07/02/2024] [Indexed: 07/13/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally, influenced by aberrant circRNA expression. Investigating circRNA-miRNA-mRNA interactions can unveil underlying mechanisms of HCC and identify potential therapeutic targets. METHODS In this study, we conducted differential analyses of mRNAs, miRNAs, and circRNAs, and established their relationships using various databases such as miRanda, miRDB, and miTarBase. Additionally, functional enrichment and immune infiltration analyses were performed to evaluate the roles of key genes. We also conducted qPCR assays and western blotting (WB) to examine the expression levels of circRNA, CCL25, and MAP2K1 in both HCC cells and clinical samples. Furthermore, we utilized overexpression and knockdown techniques for circ_0000069 and conducted wound healing, transwell invasion assays, and a tumorigenesis experiment to assess the migratory and invasive abilities of HCC cells. RESULTS Our findings revealed significant differential expression of 612 upregulated genes and 1173 downregulated genes in HCC samples compared to normal liver tissue. Additionally, 429 upregulated circRNAs and 453 downregulated circRNAs were identified. Significantly, circ_0000069 exhibited upregulation in HCC tissues and cell lines. The overexpression of circ_0000069 notably increased the invasion and migration capacity of Huh7 cells, whereas the downregulation of circ_0000069 reduced this capability in HepG2 cells. Furthermore, this effect was counteracted by CCL25 silencing or overexpression, separately. Animal studies further confirmed that the overexpression of hsa_circ_0000069 facilitated tumor growth in xenografted nude mice, while the inhibition of CCL25 attenuated this effect. CONCLUSION Circ_0000069 appears to promote HCC progression by regulating CCL25, suggesting that both circ_0000069 and CCL25 can serve as potential therapeutic targets.
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Affiliation(s)
- Junshao Zeng
- Department of Oncology, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang City People's Hospital, Guigang, Guangxi, China
| | - Yi Feng
- Department of Clinical Laboratory, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang City People's Hospital, No. 1, Zhong Shan Road, Guigang, 537100, Guangxi, China
| | - Liwen Lin
- Department of Clinical Laboratory, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang City People's Hospital, No. 1, Zhong Shan Road, Guigang, 537100, Guangxi, China
| | - Huifeng Ye
- Department of Clinical Laboratory, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang City People's Hospital, No. 1, Zhong Shan Road, Guigang, 537100, Guangxi, China
| | - Haoming Shen
- Department of Clinical Laboratory, Hunan Cancer Hospital &, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
| | - Yifan Sun
- Department of Clinical Laboratory, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang City People's Hospital, No. 1, Zhong Shan Road, Guigang, 537100, Guangxi, China.
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Li D, Wan M, Liu X, Ojha SC, Sheng Y, Li Y, Sun C, Deng C. PART1 facilitates tumorigenesis and inhibits ferroptosis by regulating the miR-490-3p/SLC7A11 axis in hepatocellular carcinoma. Aging (Albany NY) 2024; 16:11339-11358. [PMID: 39029955 PMCID: PMC11315397 DOI: 10.18632/aging.206009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 06/10/2024] [Indexed: 07/21/2024]
Abstract
BACKGROUND Ferroptosis is associated with cancer progression and has a promising application for treating hepatocellular carcinoma (HCC). Long non-coding RNA (lncRNA) participates widely in the regulation of ferroptosis, but the key lncRNA regulators implicated in ferroptosis and their molecular mechanisms remain to be identified. METHODS Bioinformatic analysis was performed in R based on The Cancer Genome Atlas Program (TCGA) public database. The relative expression of genes was detected by real-time quantitative PCR. Cell viability was assessed by the CCK8 assay. The cell cycle and apoptosis were detected by flow cytometry. Migration and invasion of HCC cells were detected by Transwell assay and wound healing assay. Expression of relevant proteins was detected by Western blotting. A dual-luciferase reporter assay was used to detect interactions between PART1 (or SLC7A11) and miR-490-3p. RESULTS The PART1/miR-490-3p/SLC7A11 axis was identified as a potential regulatory pathway of ferroptosis in HCC. PART1 silencing reduced HCC cell proliferation, migration, and metastasis and promoted apoptosis and erastin-reduced ferroptosis. Further investigation revealed that PART1 acted as a competitive endogenous RNA (ceRNA) for miR-490-3p to enhance SLC7A11 expression. Overexpression of miR-490-3p downregulated the expression of SLC7A11, inhibiting the proliferation, invasion, and metastasis of HCC cells while promoting apoptosis and erastin-induced ferroptosis. Knockdown of PART1 in HCC cells significantly improved the sensitivity of HCC cells to sorafenib. CONCLUSION Our results revealed that the PART1/miR-490-3p/SLC7A11 axis enhances HCC cell malignancy and suppresses ferroptosis, which provides a new perspective for understanding of the function of long chain non-coding RNAs in HCC. The PART1/miR-490-3p/SLC7A11 axis may be target for improving sorafenib sensitivity in HCC.
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Affiliation(s)
- Decheng Li
- Department of Infectious Diseases, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
- Laboratory of Infection and Immunity, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Meiling Wan
- Department of Infectious Diseases, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
- Laboratory of Infection and Immunity, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Xiaoling Liu
- Department of Infectious Diseases, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
- Laboratory of Infection and Immunity, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Suvash Chandra Ojha
- Department of Infectious Diseases, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
- Laboratory of Infection and Immunity, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Yunjian Sheng
- Department of Infectious Diseases, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
- Laboratory of Infection and Immunity, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Yaling Li
- Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Changfeng Sun
- Department of Infectious Diseases, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
- Laboratory of Infection and Immunity, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Cunliang Deng
- Department of Infectious Diseases, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
- Laboratory of Infection and Immunity, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
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Ge J, Tao M, Zhang G, Cai J, Li D, Tao L. New HCC Subtypes Based on CD8 Tex-Related lncRNA Signature Could Predict Prognosis, Immunological and Drug Sensitivity Characteristics of Hepatocellular Carcinoma. J Hepatocell Carcinoma 2024; 11:1331-1355. [PMID: 38983937 PMCID: PMC11232885 DOI: 10.2147/jhc.s459150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 06/28/2024] [Indexed: 07/11/2024] Open
Abstract
Purpose Hepatocellular carcinoma has become one of the severe diseases threatening human health. T cell exhaustion is deemed as a reason for immunotherapy resistance. However, little is known about the roles of CD8 Tex-related lncRNAs in HCC. Materials and Methods We processed single-cell RNA sequencing to identify CD8 Tex-related genes. CD8 Tex-related lncRNAs were identified based on their correlations with mRNAs. Unsupervised clustering approach was used to identify molecular clusters of CD8 Tex-related lncRNAs. Differences in prognosis and immune infiltration between the clusters were explored. Machine learning algorithms were used to construct a prognostic signature. Samples were classified as low- and high-risk groups based on their risk scores. We identified prognosis-related lncRNAs and constructed a ceRNA network. In vitro experiments were conducted to investigate the impacts of CD8 Tex-related lncRNAs on proliferation and apoptosis of HCC cells. Results We clarified cell types within two HCC single-cell datasets. We identified specific markers of CD8 Tex cells and analyzed their potential functions. Twenty-eight lncRNAs were identified as CD8 Tex-related. Based on CD8 Tex-related lncRNAs, samples were categorized into two distinct clusters, which exhibited significant differences in survival rates and immune infiltration. Ninety-six algorithm combinations were employed to establish a prognostic signature. RSF emerged as the one with the highest C-index. Patients in high- and low-risk groups exhibited marked differences in prognosis, enriched pathways, mutations and drug sensitivities. MCM3AP-AS1, MAPKAPK5-AS1 and PART1 were regarded as prognosis-related lncRNAs. A ceRNA network was constructed based on CD8 Tex-related lncRNAs and mRNAs. Experiments on cell lines and organoids indicated that downregulation of MCM3AP-AS1, MAPKAPK5-AS1 and PART1 suppressed cell proliferation and induced apoptosis. Conclusion CD8 Tex-related lncRNAs played crucial roles in HCC progression. Our findings provided new insights into the regulatory mechanisms of CD8 Tex-related lncRNAs in HCC.
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Affiliation(s)
- Jiachen Ge
- Department of Hepatobiliary Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Ming Tao
- Department of General Surgery, Peking University Third Hospital, Beijing, People's Republic of China
| | - Gaolei Zhang
- Department of Hepatobiliary Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Jianping Cai
- Department of Hepatobiliary Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Deyu Li
- Department of Hepatobiliary Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Lianyuan Tao
- Department of Hepatobiliary Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
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Pu L, Sun Y, Pu C, Zhang X, Wang D, Liu X, Guo P, Wang B, Xue L, Sun P. Machine learning-based disulfidptosis-related lncRNA signature predicts prognosis, immune infiltration and drug sensitivity in hepatocellular carcinoma. Sci Rep 2024; 14:4354. [PMID: 38388539 PMCID: PMC10883983 DOI: 10.1038/s41598-024-54115-8] [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: 09/05/2023] [Accepted: 02/08/2024] [Indexed: 02/24/2024] Open
Abstract
Disulfidptosis a new cell death mode, which can cause the death of Hepatocellular Carcinoma (HCC) cells. However, the significance of disulfidptosis-related Long non-coding RNAs (DRLs) in the prognosis and immunotherapy of HCC remains unclear. Based on The Cancer Genome Atlas (TCGA) database, we used Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression model to construct DRL Prognostic Signature (DRLPS)-based risk scores and performed Gene Expression Omnibus outside validation. Survival analysis was performed and a nomogram was constructed. Moreover, we performed functional enrichment annotation, immune infiltration and drug sensitivity analyses. Five DRLs (AL590705.3, AC072054.1, AC069307.1, AC107959.3 and ZNF232-AS1) were identified to construct prognostic signature. DRLPS-based risk scores exhibited better predictive efficacy of survival than conventional clinical features. The nomogram showed high congruence between the predicted survival and observed survival. Gene set were mainly enriched in cell proliferation, differentiation and growth function related pathways. Immune cell infiltration in the low-risk group was significantly higher than that in the high-risk group. Additionally, the high-risk group exhibited higher sensitivity to Afatinib, Fulvestrant, Gefitinib, Osimertinib, Sapitinib, and Taselisib. In conclusion, our study highlighted the potential utility of the constructed DRLPS in the prognosis prediction of HCC patients, which demonstrated promising clinical application value.
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Affiliation(s)
- Lei Pu
- The Key Laboratory of Adolescent Health Assessment and Exercise Intervention of the Ministry of Education, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, People's Republic of China
| | - Yan Sun
- Department of Veterinary Medicine, Shandong Vocational Animal Science and Veterinary College, Weifang, 261071, Shandong, People's Republic of China
| | - Cheng Pu
- School of Martial Arts, Shanghai University of Sport, Shanghai, 200438, People's Republic of China
| | - Xiaoyan Zhang
- The Key Laboratory of Adolescent Health Assessment and Exercise Intervention of the Ministry of Education, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, People's Republic of China
| | - Dong Wang
- Jiangsu Vocational Institute of Architectural Technology, Xuzhou, 221116, Jiangsu, People's Republic of China
| | - Xingning Liu
- The Key Laboratory of Adolescent Health Assessment and Exercise Intervention of the Ministry of Education, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, People's Republic of China
| | - Pin Guo
- Department of Veterinary Medicine, Shandong Vocational Animal Science and Veterinary College, Weifang, 261071, Shandong, People's Republic of China
| | - Bing Wang
- Department of Oncological Surgery, Minhang Branch of Shanghai Cancer Center, Fudan University, Shanghai, 200240, People's Republic of China.
| | - Liang Xue
- Zhejiang Institute of Sports Science, Hangzhou, 310004, Zhejiang, People's Republic of China.
| | - Peng Sun
- The Key Laboratory of Adolescent Health Assessment and Exercise Intervention of the Ministry of Education, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, People's Republic of China.
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Shen M, Zhang Q, Pan W, Wang B. CircUCK2 promotes hepatocellular carcinoma development by upregulating UCK2 in a mir-149-5p-dependent manner. Discov Oncol 2024; 15:14. [PMID: 38245591 PMCID: PMC10799813 DOI: 10.1007/s12672-024-00863-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 01/08/2024] [Indexed: 01/22/2024] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) participate in the regulation of Hepatocellular Carcinoma (HCC) progression. The objective of this study was to explore the function and mechanism of circUCK2 in HCC development. METHODS The RNA levels of circUCK2, miR-149-5p and uridine-cytidine kinase 2 (UCK2) were examined by quantitative real-time polymerase chain reaction (qRT-PCR). EdU incorporation assay and colony formation assay were respectively performed to analyze cell proliferation and colony formation. Wound healing assay and transwell assay were conducted for cell migration and invasion. Flow cytometry was used for cell apoptosis analysis. Western blot assay was conducted to determine the protein levels of E-cadherin, N-cadherin, matrix metallopeptidase 9 (MMP-9) and UCK2. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay were conducted to confirm the interaction between miR-149-5p and circUCK2 or UCK2. The xenograft model was established to explore the role of circUCK2 in tumor growth in vivo. RESULTS CircUCK2 level was elevated in HCC, and circUCK2 depletion suppressed HCC cell proliferation, colony formation, migration and invasion and accelerated cell apoptosis. Mechanistically, circUCK2 could positively modulate UCK2 expression by interacting with miR-149-5p. Furthermore, the repressive effects of circUCK2 knockdown on the malignant behaviors of HCC cells were alleviated by UCK2 overexpression or miR-149-5p inhibition. The promoting effects of circUCK2 overexpression on HCC cell malignancy were alleviated by UCK2 silencing or miR-149-5p introduction. Additionally, circUCK2 knockdown hampered tumor growth in vivo. CONCLUSION CircUCK2 contributed to HCC malignant progression in vitro and in vivo via targeting miR-149-5p/UCK2 axis, demonstrating that circUCK2 might be a novel therapeutic target for HCC.
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Affiliation(s)
- Minghai Shen
- Department of General Surgury, Xixi Hospital of Hangzhou, Hangzhou, 310023, China
| | - Qinghua Zhang
- Department of General Surgury, Xixi Hospital of Hangzhou, Hangzhou, 310023, China
| | - Wanneng Pan
- Department of General Surgury, Xixi Hospital of Hangzhou, Hangzhou, 310023, China
| | - Bei Wang
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, No. 79, Qingchun Road, Shangcheng District, Hangzhou, 310023, China.
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9
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Cui Y, Li C, Zeng X, Wei X, Li P, Cheng J, Xu Q, Yang Y. ATP purinergic receptor signalling promotes Sca-1 + cell proliferation and migration for vascular remodelling. Cell Commun Signal 2023; 21:173. [PMID: 37430253 PMCID: PMC10332060 DOI: 10.1186/s12964-023-01185-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 06/06/2023] [Indexed: 07/12/2023] Open
Abstract
AIMS Vascular resident stem cells expressing stem cell antigen-1 (Sca-1+ cells) promote vascular regeneration and remodelling following injury through migration, proliferation and differentiation. The aim of this study was to examine the contributions of ATP signalling through purinergic receptor type 2 (P2R) isoforms in promoting Sca-1+ cell migration and proliferation after vascular injury and to elucidate the main downstream signalling pathways. METHODS AND RESULTS ATP-evoked changes in isolated Sca-1+ cell migration were examined by transwell assays, proliferation by viable cell counting assays and intracellular Ca2+ signalling by fluorometry, while receptor subtype contributions and downstream signals were examined by pharmacological or genetic inhibition, immunofluorescence, Western blotting and quantitative RT-PCR. These mechanisms were further examined in mice harbouring TdTomato-labelled Sca-1+ cells with and without Sca-1+-targeted P2R knockout following femoral artery guidewire injury. Stimulation with ATP promoted cultured Sca-1+ cell migration, induced intracellular free calcium elevations primarily via P2Y2R stimulation and accelerated proliferation mainly via P2Y6R stimulation. Enhanced migration was inhibited by the ERK blocker PD98059 or P2Y2R-shRNA, while enhanced proliferation was inhibited by the P38 inhibitor SB203580. Femoral artery guidewire injury of the neointima increased the number of TdTomato-labelled Sca-1+ cells, neointimal area and the ratio of neointimal area to media area at 3 weeks post-injury, and all of these responses were reduced by P2Y2R knockdown. CONCLUSIONS ATP induces Sca-1+ cell migration through the P2Y2R-Ca2+-ERK signalling pathway, and enhances proliferation through the P2Y6R-P38-MAPK signalling pathway. Both pathways are essential for vascular remodelling following injury. Video Abstract.
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Affiliation(s)
- Yiqin Cui
- Key Lab of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological, 1-1 Xianglin Road, Luzhou, 646000, China
| | - Chunshu Li
- Key Lab of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological, 1-1 Xianglin Road, Luzhou, 646000, China
| | - Xinyi Zeng
- Key Lab of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological, 1-1 Xianglin Road, Luzhou, 646000, China
| | - Xiaoyu Wei
- Key Lab of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological, 1-1 Xianglin Road, Luzhou, 646000, China
| | - Pengyun Li
- Key Lab of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological, 1-1 Xianglin Road, Luzhou, 646000, China
| | - Jun Cheng
- Key Lab of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological, 1-1 Xianglin Road, Luzhou, 646000, China
| | - Qingbo Xu
- Key Lab of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological, 1-1 Xianglin Road, Luzhou, 646000, China.
| | - Yan Yang
- Key Lab of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological, 1-1 Xianglin Road, Luzhou, 646000, China.
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10
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Hashemi M, Mirzaei S, Zandieh MA, Rezaei S, Amirabbas Kakavand, Dehghanpour A, Esmaeili N, Ghahremanzade A, Saebfar H, Heidari H, Salimimoghadam S, Taheriazam A, Entezari M, Ahn KS. Long non-coding RNAs (lncRNAs) in hepatocellular carcinoma progression: Biological functions and new therapeutic targets. PROGRESS IN BIOPHYSICS AND MOLECULAR BIOLOGY 2023; 177:207-228. [PMID: 36584761 DOI: 10.1016/j.pbiomolbio.2022.12.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 11/29/2022] [Accepted: 12/22/2022] [Indexed: 12/28/2022]
Abstract
Liver is an important organ in body that performs vital functions such as detoxification. Liver is susceptible to development of cancers, and hepatocellular carcinoma (HCC) is among them. 75-85% of liver cancer cases are related to HCC. Therefore, much attention has been directed towards understanding factors mediating HCC progression. LncRNAs are epigenetic factors with more than 200 nucleotides in length located in both nucleus and cytoplasm and they are promising candidates in cancer therapy. Directing studies towards understanding function of lncRNAs in HCC is of importance. LncRNAs regulate cell cycle progression and growth of HCC cells, and they can also induce/inhibit apoptosis in tumor cells. LncRNAs affect invasion and metastasis in HCC mainly by epithelial-mesenchymal transition (EMT) mechanism. Revealing the association between lncRNAs and downstream signaling pathways in HCC is discussed in the current manuscript. Infectious diseases can affect lncRNA expression in mediating HCC development and then, altered expression level of lncRNA is associated with drug resistance and radio-resistance. Biomarker application of lncRNAs and their role in prognosis and diagnosis of HCC are also discussed to pave the way for treatment of HCC patients.
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Affiliation(s)
- Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Sepideh Mirzaei
- Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Mohammad Arad Zandieh
- Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Sahar Rezaei
- Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Amirabbas Kakavand
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Amir Dehghanpour
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Negin Esmaeili
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Azin Ghahremanzade
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Hamidreza Saebfar
- European University Association, League of European Research Universities, University of Milan, Italy
| | - Hajar Heidari
- Department of Biomedical Sciences, School of Public Health University at Albany State University of New York, Albany, NY, 12208, USA
| | - Shokooh Salimimoghadam
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Afshin Taheriazam
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Maliheh Entezari
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Kwang Seok Ahn
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
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11
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Ghafouri-Fard S, Harsij A, Hussen BM, Abdullah SR, Baniahmad A, Taheri M, Sharifi G. A review on the role of long non-coding RNA prostate androgen-regulated transcript 1 (PART1) in the etiology of different disorders. Front Cell Dev Biol 2023; 11:1124615. [PMID: 36875771 PMCID: PMC9974648 DOI: 10.3389/fcell.2023.1124615] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 02/06/2023] [Indexed: 02/17/2023] Open
Abstract
LncRNA prostate androgen-regulated transcript 1 (PART1) is an important lncRNA in the carcinogenesis whose role has been firstly unraveled in prostate cancer. Expression of this lncRNA is activated by androgen in prostate cancer cells. In addition, this lncRNA has a role in the pathogenesis intervertebral disc degeneration, myocardial ischemia-reperfusion injury, osteoarthritis, osteoporosis and Parkinson's disease. Diagnostic role of PART1 has been assessed in some types of cancers. Moreover, dysregulation of PART1 expression is regarded as a prognostic factor in a variety of cancers. The current review provides a concise but comprehensive summary of the role of PART1 in different cancers and non-malignant disorders.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atefeh Harsij
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bashdar Mahmud Hussen
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Kurdistan Region, Iraq
| | - Snur Rasool Abdullah
- Medical Laboratory Science, Lebanese French University, Erbil, Kurdistan Region, Iraq
| | - Aria Baniahmad
- Institute of Human Genetics, Jena University Hospital, Jena, Germany
| | - Mohammad Taheri
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Guive Sharifi
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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12
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MicroRNA-34c-5p exhibits anticancer properties in gastric cancer by targeting MAP2K1 to inhibit cell proliferation, migration, and invasion. BIOMED RESEARCH INTERNATIONAL 2022; 2022:7375661. [PMID: 36203485 PMCID: PMC9532111 DOI: 10.1155/2022/7375661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 08/27/2022] [Indexed: 12/02/2022]
Abstract
Purpose Gastric cancer(GC)is one of the deadliest digestive tract tumors worldwide，existing studies suggest that dysregulated expression of microRNAs (miRNAs) plays an important role in the pathogenesis and progression of GC. This study aimed to investigate the expression, biological function, and downstream mechanism of miR-34c-5p in GC, provide new targets for gastric cancer diagnosis and treatment. Methods The expression of miR-34c-5p in GC tissues and cell lines was examined by RT-qPCR. Cell wound healing, transwell and cell cloning assays were used to detect the effect of miR-34c-5p on the migration and invasion abilities, respectively, of GC cells. Western blot was performed to detect the expression of related proteins. Bioinformatics analysis was used to predict the binding of MAP2K1 to miR-34c-5p and the targeting relationship was confirmed by dual luciferase reporter assay. Results The expression level of miR-34c-5p was significantly decreased in GC tissues and cell lines. miR-34c-5p overexpression inhibited migration, invasion, and colony formation of gastric cancer cells, the related protein E-cadherin expression was significantly increased and N-cadherin, vimentin, and PCNA expression were significantly decreased, while miR-34c-5p knockdown exerted the opposite effects. In addition, the targeting relationship between miR-34c-5p and MAP2K1 was predicted and confirmed, and further confirmed by rescue experiments that MAP2K1 alleviated the inhibitory effect of miR-34c-5p in GC. Conclusion MiR-34c-5p is lowly expressed in GC, and it can target MAP2K1 to exert inhibitory effects on GC proliferation, invasion, and migration. These findings provide a promising biomarker and a potential therapeutic target for gastric cancer.
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13
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Tumor-Suppressive and Oncogenic Roles of microRNA-149-5p in Human Cancers. Int J Mol Sci 2022; 23:ijms231810823. [PMID: 36142734 PMCID: PMC9501226 DOI: 10.3390/ijms231810823] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/07/2022] [Accepted: 09/14/2022] [Indexed: 12/24/2022] Open
Abstract
Malignant tumors are always a critical threat to human health, with complex pathogenesis, numerous causative factors, and poor prognosis. The features of cancers, such as gene mutations, epigenetic alterations, and the activation and inhibition of signaling pathways in the organism, play important roles in tumorigenesis and prognosis. MicroRNA (miRNA) enables the control of various molecular mechanisms and plays a variety of roles in human cancers, such as radiation sensitivity and tumor immunity, through the regulation of target genes. MiR-149-5p participates in the process and is closely related to lipogenesis, the migration of vascular endothelial cells, and the expression of stem-cell-related proteins. In recent years, its role in cancer has dramatically increased. In this review, we summarize the regular physiological roles of miRNAs, specifically miR-149-5p, in the organism and discuss the tumor-suppressive or oncogenic roles of miR-149-5p in different human cancers with respect to signaling pathways involved in regulation. Possible clinical applications of miR-149-5p in future targeted therapies and prognosis improvement in oncology are suggested.
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14
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Ran R, Gong CY, Wang ZQ, Zhou WM, Zhang SB, Shi YQ, Ma CW, Zhang HH. Long non‑coding RNA PART1: dual role in cancer. Hum Cell 2022; 35:1364-1374. [PMID: 35864416 DOI: 10.1007/s13577-022-00752-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 07/14/2022] [Indexed: 12/24/2022]
Abstract
Increasing evidence has shown that long non-coding RNAs (lncRNAs), which are non-coding endogenous single-stranded RNAs, play an essential role in various physiological and pathological processes through transcriptional interference, post-transcriptional regulation, and epigenetic modification. Moreover, lncRNAs, as oncogenes or tumor suppressor genes, play an important role in the occurrence and development of human cancers. Prostate androgen-regulated transcript 1 (PART1) was initially identified as a carcinogenic lncRNA in prostate adenomas. The upregulated expression of PART1 plays a tumor-promoting role in liver, prostate, lung cancers, and other tumors. In contrast, the expression of PART1 is downregulated in esophageal squamous cell carcinoma, glioma, and other tumors, which may inhibit the tumor. PART1 plays a dual role in cancer and regulates cell proliferation, apoptosis, invasion, and metastasis through a variety of potential mechanisms. These findings suggest that PART1 is a promising tumor biomarker and therapeutic target. This article reviews the biological functions, related mechanisms, and potential clinical significance of PART1 in a variety of human cancers.
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Affiliation(s)
- Rui Ran
- Lanzhou University Second Hospital, 82 Cuiying Men, Lanzhou, 730000, People's Republic of China.,Orthopaedics Key Laboratory of Gansu Province, Lanzhou, 730000, People's Republic of China
| | - Chao-Yang Gong
- Lanzhou University Second Hospital, 82 Cuiying Men, Lanzhou, 730000, People's Republic of China.,Orthopaedics Key Laboratory of Gansu Province, Lanzhou, 730000, People's Republic of China
| | - Zhi-Qiang Wang
- Lanzhou University Second Hospital, 82 Cuiying Men, Lanzhou, 730000, People's Republic of China.,Orthopaedics Key Laboratory of Gansu Province, Lanzhou, 730000, People's Republic of China
| | - Wen-Ming Zhou
- Lanzhou University Second Hospital, 82 Cuiying Men, Lanzhou, 730000, People's Republic of China.,Orthopaedics Key Laboratory of Gansu Province, Lanzhou, 730000, People's Republic of China
| | - Shun-Bai Zhang
- Lanzhou University Second Hospital, 82 Cuiying Men, Lanzhou, 730000, People's Republic of China.,Orthopaedics Key Laboratory of Gansu Province, Lanzhou, 730000, People's Republic of China
| | - Yong-Qiang Shi
- Lanzhou University Second Hospital, 82 Cuiying Men, Lanzhou, 730000, People's Republic of China.,Orthopaedics Key Laboratory of Gansu Province, Lanzhou, 730000, People's Republic of China
| | - Chun-Wei Ma
- Lanzhou University Second Hospital, 82 Cuiying Men, Lanzhou, 730000, People's Republic of China.,Orthopaedics Key Laboratory of Gansu Province, Lanzhou, 730000, People's Republic of China
| | - Hai-Hong Zhang
- Lanzhou University Second Hospital, 82 Cuiying Men, Lanzhou, 730000, People's Republic of China.
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15
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Abstract
The tumor microenvironment (TME) is a well-recognized system that plays an essential role in tumor initiation, development, and progression. Intense intercellular communication between tumor cells and other cells (especially macrophages) occurs in the TME and is mediated by cell-to-cell contact and/or soluble messengers. Emerging evidence indicates that noncoding RNAs (ncRNAs) are critical regulators of the relationship between cells within the TME. In this review, we provide an update on the regulation of ncRNAs (primarily micro RNAs [miRNAs], long ncRNAs [lncRNAs], and circular RNAs [circRNAs]) in the crosstalk between macrophages and tumor cells in hepatocellular carcinoma (HCC). These ncRNAs are derived from macrophages or tumor cells and act as oncogenes or tumor suppressors, contributing to tumor progression not only by regulating the physiological and pathological processes of tumor cells but also by controlling macrophage infiltration, activation, polarization, and function. Herein, we also explore the options available for clinical therapeutic strategies targeting crosstalk-related ncRNAs to treat HCC. A better understanding of the relationship between macrophages and tumor cells mediated by ncRNAs will uncover new diagnostic biomarkers and pharmacological targets in cancer.
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16
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Chen MJ, Fei JG, Song ZW, Chen F. Long non-coding RNA PART1 in cancer: Friend or foe? Dig Liver Dis 2022; 54:709. [PMID: 35016858 DOI: 10.1016/j.dld.2021.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 12/14/2021] [Indexed: 12/11/2022]
Affiliation(s)
- Min-Jie Chen
- Department of Hepatobiliary Surgery, Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, PR China
| | - Jian-Guo Fei
- Department of Hepatobiliary Surgery, Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, PR China
| | - Zheng-Wei Song
- Department of Hepatobiliary Surgery, Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, PR China.
| | - Fei Chen
- Department of Hepatobiliary Surgery, Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, PR China.
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17
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Cai S, Du R, Zhang Y, Yuan Z, Shang J, Yang Y, Han B, Zhong W, Yuan H, Li Z. Construction and Comprehensive Analysis of ceRNA Networks and Tumor-Infiltrating Immune Cells in Hepatocellular Carcinoma With Vascular Invasion. FRONTIERS IN BIOINFORMATICS 2022; 2:836981. [PMID: 36304284 PMCID: PMC9580849 DOI: 10.3389/fbinf.2022.836981] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Accepted: 03/23/2022] [Indexed: 12/24/2022] Open
Abstract
Background: Hepatocellular carcinoma (HCC) is a common malignant cancer. Metastasis plays a critical role in tumor progression, and vascular invasion is considered one of the most crucial factors for HCC metastasis. However, comprehensive analysis focusing on competitive endogenous RNA (ceRNA) and immune infiltration in the vascular invasion of HCC is lacking. Methods: The gene expression profiles of 321 samples, including 210 primary HCC cases and 111 HCC cases with vascular invasion, were downloaded from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma project, and used in identifying significant differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs). The RNAs associated with vascular invasion were used in constructing a ceRNA network. A multigene-based risk signature was constructed using the least absolute shrinkage and selection operator algorithm. We detected the fractions of 28 immune cell types in HCC through single-sample gene set enrichment analysis (ssGSEA). Finally, the relationship between the ceRNA network and immune cells was determined through correlation analysis and used in clarifying the potential mechanism involved in vascular invasion. Results: Overall, 413 DElncRNAs, 27 DEmiRNAs, and 397 DEmRNAs were recognized in HCC. A specific ceRNA network based on the interaction among 3 lncRNA–miRNA pairs and 24 miRNA–mRNA pairs were established. A ceRNA-based prognostic signature was constructed and used in dividing samples into high- and low-risk subgroups. The signature showed significant efficacy; its 3- and 5-year areas under the receiver operating characteristic curves were 0.712 and 0.653, respectively. ceRNA and ssGSEA integration analysis demonstrated that PART1 (p = 0, R = −0.33) and CDK5R2 (p = 0.01, R = −0.15) were negatively correlated to natural killer cells. Conclusion: This study demonstrated that vascular invasion in HCC might be related to PART1, and its role in regulating CDK5R2 and NK cells. A nomogram was developed to predict the prognosis of patients with HCC and demonstrated the value of the ceRNA network and tumor-infiltrating immune cells value in improving personalized management.
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Affiliation(s)
- Shijiao Cai
- Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin, China
| | - Renle Du
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Yuan Zhang
- Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin, China
| | - Zhengyi Yuan
- Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin, China
| | - Jie Shang
- Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin, China
| | - Yang Yang
- Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin, China
| | - Bin Han
- Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin, China
| | - Weilong Zhong
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- *Correspondence: Weilong Zhong, ; Hengjie Yuan, ; Zhengxiang Li,
| | - Hengjie Yuan
- Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin, China
- *Correspondence: Weilong Zhong, ; Hengjie Yuan, ; Zhengxiang Li,
| | - Zhengxiang Li
- Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin, China
- *Correspondence: Weilong Zhong, ; Hengjie Yuan, ; Zhengxiang Li,
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Wang Y, Jiang F, Chen F, Zhang D, Wang J. LncRNA XIST engages in psoriasis via sponging miR-338-5p to regulate keratinocyte proliferation and inflammation. Skin Pharmacol Physiol 2022; 35:196-205. [PMID: 35231918 DOI: 10.1159/000523781] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 02/24/2022] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Psoriasis is an immune-mediated polygenic inflammatory skin disease, keratinocyte proliferation is an important mechanism. The study investigated the role and regulatory relationship between lncRNA XIST and miR-338-5p in psoriatic patients and cell models. METHODS Serum samples were collected from 55 psoriasis patients. HaCaT was recruited for the cell experiments, and induced by M5 cytokines to mimic psoriasis in vitro. XIST and miR-338-5p levels were detected via qRT-PCR. Cell viability under different treatments was evaluated using CCK-8. ELISA was applied to measure the concentration of inflammatory cytokines. The regulatory relationship was confirmed using luciferase reporter gene assay. RESULTS Serum XIST was elevated in patients with psoriasis, and can distinguish the psoriasis patients from healthy controls according to the ROC curve. High level of XIST was positively correlated with with PASI score and serum TNF-α, IL-17A and IL-22 concentrations in psoriasis patients. XIST silencing suppressed M5-induced keratinocyte proliferation and restrained the discharge of inflammatory cytokines (TNF-α, IL-17A, IL-22) and chemokines (CXCL1, CXCL8, CCL20). XIST can sponge miR-338-5p, and miR-338-5p downregulation abolished the inhibitory effect of XIST silencing on cell proliferation and inflammation. miR-338-5p was at high expression in the clinical serum samples from psoriasis patients. The target relationship between miR-338-5p and IL-6 was proved. CONCLUSION LncRNA XIST is highly expressed in the serum of patients with psoriasis, and was positively correlated with disease severity and inflammation. XIST may regulate keratinocyte proliferation and inflammation via regulating miR-338-5p/IL-6 axis.
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Affiliation(s)
- Yitao Wang
- Department of Laboratory, Weihai Municipal Hospital, Weihai, China
| | - Feifei Jiang
- Department of Laboratory, Weihai Maternal and Child Health Care Hospital, Weihai, China
| | - Fang Chen
- Department of Medical Aesthetics, Linyi Central Hospital, Linyi, China
| | - Dapeng Zhang
- Department of Burn Plastic Surgery, Binzhou Medical University Hospital, Binzhou, China
| | - Jian Wang
- Department of Laboratory, Yidu Central Hospital of Weifang, Weifang, China
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Yao J, Hua X, Shi J, Hu X, Lui K, He K, Mai J, Lan T, Lu M. LncRNA THEMIS2-211, a tumor-originated circulating exosomal biomarker, promotes the growth and metastasis of hepatocellular carcinoma by functioning as a competing endogenous RNA. FASEB J 2022; 36:e22238. [PMID: 35224785 DOI: 10.1096/fj.202101564r] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 02/03/2022] [Accepted: 02/16/2022] [Indexed: 12/11/2022]
Abstract
Hepatocellular carcinoma (HCC) is a major challenge for human health. Finding reliable diagnostic biomarkers and therapeutic targets for HCC is highly desired in the clinic. Currently, circulating exosomal lncRNA is a promising biomarker for the diagnosis of cancer and lncRNA is also a potential target in cancer therapy. Here, the diagnostic value of a panel based on exosomal lncRNA THEMIS2-211 and PRKACA-202, superior to that of AFP, was identified for diagnosing human HCC. Besides, the performance of exosomal lncRNA THEMIS2-211 alone exceeds that of AFP in diagnosing early-stage HCC patients (stage I). Furthermore, lncRNA THEMIS2-211 is highly expressed in HCC tissues and correlated with the poor prognosis of HCC patients. LncRNA THEMIS2-211 is upregulated and localized in the cytoplasm of HCC cells. LncRNA THEMIS2-211 exerts its biological function as an oncogene that promotes the proliferation, migration, invasion, EMT of HCC cells by physically interacting with miR-940 and therefore promoting SPOCK1 expressions. Rescue assays show the regulation of SPOCK1 by lncRNA THEMIS2-211 dependents on miR-940. The discovery of lncRNA THEMIS2-211 further illuminates the molecular pathogenesis of HCC and the THEMIS2-211/miR-940/SPOCK1 axis may act as a potential therapeutic target for HCC.
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Affiliation(s)
- Jiyou Yao
- Department of HBP SURGERY II, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, People's Republic of China
| | - Xuefeng Hua
- Department of HBP SURGERY II, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, People's Republic of China
| | - Jiewei Shi
- Department of HBP SURGERY II, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, People's Republic of China
| | - Xiaoyuan Hu
- Department of HBP SURGERY II, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, People's Republic of China
| | - Kayin Lui
- The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Kaitao He
- Department of HBP SURGERY II, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, People's Republic of China
| | - Jialuo Mai
- Department of HBP SURGERY II, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, People's Republic of China
| | - Tian Lan
- Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China
| | - Minqiang Lu
- Department of HBP SURGERY II, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, People's Republic of China
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20
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Liu L, Wang H, Yu S, Gao X, Liu G, Sun D, Jiang X. An Update on the Roles of circRNA-ZFR in Human Malignant Tumors. Front Cell Dev Biol 2022; 9:806181. [PMID: 35186956 PMCID: PMC8848330 DOI: 10.3389/fcell.2021.806181] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Accepted: 12/16/2021] [Indexed: 01/11/2023] Open
Abstract
CircRNAs (circular RNAs) are single-stranded RNAs that form covalently closed loops and function as important regulatory elements of the genome through multiple mechanisms. Increasing evidence had indicated that circRNAs, which might serve as either oncogenes or tumor suppressors, played vital roles in the pathophysiology of human diseases, especially in tumorigenesis and progression. CircRNA-ZFR (circular RNA zinc finger RNA binding protein) is a circular RNA that had attracted much attention in recent years. It has been found that circRNA-ZFR was abnormally expressed in a variety of malignant tumors, and its dysregulated expression was closely related to tumor stage, cancer metastasis and patients’ prognosis. Recent studies had shown that aberrantly expressed circRNA-ZFR could regulate the malignant biological behaviors of tumors through various mechanisms; further exploration of circRNA-ZFR expression in tumors and its regulation on malignant biological behaviors such as tumor proliferation, invasion and drug resistance will provide new ideas for clinical tumors diagnosis and treatment.
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21
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A Review on the Role of miR-149-5p in the Carcinogenesis. Int J Mol Sci 2021; 23:ijms23010415. [PMID: 35008841 PMCID: PMC8745060 DOI: 10.3390/ijms23010415] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 12/28/2021] [Accepted: 12/29/2021] [Indexed: 02/07/2023] Open
Abstract
miR-149 is an miRNA with essential roles in carcinogenesis. This miRNA is encoded by the MIR149 gene on 2q37.3. The miR-149 hairpin produces miR-149-5p and miR-149-3p, which are the “guide” and the sister “passenger” strands, respectively. Deep sequencing experiments have shown higher prevalence of miR-149-5p compared with miR-149-3p. Notably, both oncogenic and tumor suppressive roles have been reported for miR-149-5p. In this review, we summarize the impact of miR-149-5p in the tumorigenesis and elaborate mechanisms of its involvement in this process in a variety of neoplastic conditions based on three lines of evidence, i.e., in vitro, in vivo and clinical settings.
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22
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Ren FJ, Yao Y, Cai XY, Cai YT, Su Q, Fang GY. MiR-149-5p: An Important miRNA Regulated by Competing Endogenous RNAs in Diverse Human Cancers. Front Oncol 2021; 11:743077. [PMID: 34722295 PMCID: PMC8554335 DOI: 10.3389/fonc.2021.743077] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Accepted: 10/01/2021] [Indexed: 12/11/2022] Open
Abstract
MicroRNAs (miRNAs) consist of a large family of small, non-coding RNAs with the ability to result in gene silencing post-transcriptionally. With recent advances in research technology over the past several years, the physiological and pathological potentials of miRNAs have been gradually uncovered. MiR-149-5p, a conserved miRNA, was found to regulate physiological processes, such as inflammatory response, adipogenesis and cell proliferation. Notably, increasing studies indicate miR-149-5p may act as an important regulator in solid tumors, especially cancers in reproductive system and digestive system. It has been acknowledged that miR-149-5p can function as an oncogene or tumor suppressor in different cancers, which is achieved by controlling a variety of genes expression and adjusting downstream signaling pathway. Moreover, the levels of miR-149-5p are influenced by several newly discovered long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). However, there is blank about systematic function and mechanism of miR-149-5p in human cancers. In this review, we firstly summarize the present comprehension of miR-149-5p at the molecular level, its vital role in tumor initiation and progression, as well as its potential roles in monitoring diverse reproductive and digestive malignancies.
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Affiliation(s)
- Fu-jia Ren
- Department of Pharmacy, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, China
| | - Yao Yao
- Department of Pharmacy, Women’s Hospital School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiao-yu Cai
- Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yu-ting Cai
- Department of Pharmacy, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, China
| | - Qian Su
- Department of Pharmacy, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, China
| | - Guo-ying Fang
- Department of Pharmacy, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, China
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23
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Chen J, Meng E, Lin Y, Shen Y, Hu C, Zhou G, Yuan C. The Role of Tumor-related LncRNA PART1 in cancer. Curr Pharm Des 2021; 27:4152-4159. [PMID: 34225608 DOI: 10.2174/1381612827666210705161955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 06/01/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND As we all know, long non-coding RNA (lncRNA) affects tumor progression, which has caused a great upsurge in recent years. It can also affect the growth, migration, and invasion of tumors. When we refer to the abnormal expression of lncRNA, we will find it associated with malignant tumors. In addition, lncRNA has been proved to be a key targeted gene for the treatment of some diseases. PART1, a member of lncRNA, has been reported as a regulator in the process of tumor occurrence and development. This study aims to reveal the biological functions, specific mechanisms, and clinical significance of PART1 in various tumor cells. METHODS Through the careful search of PUBMED, the mechanisms of the effect of PART1 on tumorigenesis and development are summarized. RESULTS On the one hand, the up-regulated expression of PART1 plays a tumor-promoting role in tumors, including lung cancer, prostate cancer, bladder cancer and so on. On the other hand, PART1 is down-regulated in gastric cancer, glioma and other tumors to play a tumor inhibitory role. In addition, PART1 regulates tumor growth mainly by targeting microRNA such as miR-635, directly regulating the expression of proteins such as FUS/EZH2, affecting signal pathways such as the Toll-like receptor pathway, or regulating immune cells. CONCLUSION PART1 is closely related to tumors by regulating a variety of molecular mechanisms. In addition, PART1 can be used as a clinical marker for the early diagnosis of tumors and plays an important role in tumor-targeted therapy.
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Affiliation(s)
- Jinlan Chen
- College of Medical Science, China Three Gorges University, Yichang 443002, China
| | - Enqing Meng
- College of Medical Science, China Three Gorges University, Yichang 443002, China
| | - Yexiang Lin
- College of Medical Science, China Three Gorges University, Yichang 443002, China
| | - Yujie Shen
- College of Medical Science, China Three Gorges University, Yichang 443002, China
| | - Chengyu Hu
- College of Medical Science, China Three Gorges University, Yichang 443002, China
| | - Gang Zhou
- College of Traditional Chinese Medicine, China Three Gorges University, Yichang, China
| | - Chengfu Yuan
- College of Medical Science, China Three Gorges University, Yichang 443002, China
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24
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Liang J, Zhi Y, Deng W, Zhou W, Li X, Cai Z, Zhu Z, Zeng J, Wu W, Dong Y, Huang J, Zhang Y, Xu S, Feng Y, Ding F, Zhang J. Development and validation of ferroptosis-related lncRNAs signature for hepatocellular carcinoma. PeerJ 2021; 9:e11627. [PMID: 34178478 PMCID: PMC8202323 DOI: 10.7717/peerj.11627] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 05/26/2021] [Indexed: 12/24/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) with high heterogeneity is one of the most frequent malignant tumors throughout the world. However, there is no research to establish a ferroptosis-related lncRNAs (FRlncRNAs) signature for the patients with HCC. Therefore, this study was designed to establish a novel FRlncRNAs signature to predict the survival of patients with HCC. Method The expression profiles of lncRNAs were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. FRlncRNAs co-expressed with ferroptosis-related genes were utilized to establish a signature. Cox regression was used to construct a novel three FRlncRNAs signature in the TCGA cohort, which was verified in the GEO validation cohort. Results Three differently expressed FRlncRNAs significantly associated with prognosis of HCC were identified, which composed a novel FRlncRNAs signature. According to the FRlncRNAs signature, the patients with HCC could be divided into low- and high-risk groups. Patients with HCC in the high-risk group displayed shorter overall survival (OS) contrasted with those in the low-risk group (P < 0.001 in TCGA cohort and P = 0.045 in GEO cohort). This signature could serve as a significantly independent predictor in Cox regression (multivariate HR > 1, P < 0.001), which was verified to a certain extent in the GEO cohort (univariate HR > 1, P < 0.05). Meanwhile, it was also a useful tool in predicting survival among each stratum of gender, age, grade, stage, and etiology,etc. This signature was connected with immune cell infiltration (i.e., Macrophage, Myeloid dendritic cell, and Neutrophil cell, etc.) and immune checkpoint blockade targets (PD-1, CTLA-4, and TIM-3). Conclusion The three FRlncRNAs might be potential therapeutic targets for patients, and their signature could be utilized for prognostic prediction in HCC.
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Affiliation(s)
- Jiaying Liang
- Guangzhou University of Chinese Medicine, School of Basic Medical Sciences, Guangzhou, China.,Guangzhou University of Chinese Medicine, Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou, China
| | - Yaofeng Zhi
- Guangzhou University of Chinese Medicine, School of Basic Medical Sciences, Guangzhou, China.,Guangzhou University of Chinese Medicine, Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou, China
| | - Wenhui Deng
- Guangzhou University of Chinese Medicine, The fourth Affiliated Hospital of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Weige Zhou
- Guangzhou University of Chinese Medicine, School of Basic Medical Sciences, Guangzhou, China
| | - Xuejun Li
- Guangzhou University of Chinese Medicine, School of Basic Medical Sciences, Guangzhou, China
| | - Zheyou Cai
- Guangzhou University of Chinese Medicine, School of Basic Medical Sciences, Guangzhou, China
| | - Zhijian Zhu
- Guangzhou University of Chinese Medicine, School of Basic Medical Sciences, Guangzhou, China
| | - Jinxiang Zeng
- Guangzhou University of Chinese Medicine, School of Basic Medical Sciences, Guangzhou, China
| | - Wanlan Wu
- Guangzhou University of Chinese Medicine, School of Basic Medical Sciences, Guangzhou, China
| | - Ying Dong
- Guangzhou University of Chinese Medicine, School of Basic Medical Sciences, Guangzhou, China
| | - Jin Huang
- Guangzhou University of Chinese Medicine, Clinic of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yuzhuo Zhang
- Guangzhou University of Chinese Medicine, School of Basic Medical Sciences, Guangzhou, China.,Guangzhou University of Chinese Medicine, Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou, China
| | - Shichao Xu
- Guangzhou University of Chinese Medicine, School of Basic Medical Sciences, Guangzhou, China.,Guangzhou University of Chinese Medicine, Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou, China
| | - Yixin Feng
- Guangzhou University of Chinese Medicine, School of Basic Medical Sciences, Guangzhou, China.,Guangzhou University of Chinese Medicine, Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou, China
| | - Fuping Ding
- Guangzhou University of Chinese Medicine, School of Nursing, Guangzhou, China
| | - Jin Zhang
- Guangzhou University of Chinese Medicine, School of Basic Medical Sciences, Guangzhou, China.,Guangzhou University of Chinese Medicine, Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou, China
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25
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Yang H, Zhang X, Zhu L, Yang Y, Yin X. YY1-Induced lncRNA PART1 Enhanced Resistance of Ovarian Cancer Cells to Cisplatin by Regulating miR-512-3p/CHRAC1 Axis. DNA Cell Biol 2021; 40:821-832. [PMID: 34030482 DOI: 10.1089/dna.2021.0059] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Chemoresistance is one of the major obstacles encountered in ovarian cancer (OC) therapy. Long noncoding RNA PART1 has been reported to be involved in the tumorigenesis of several types of cancers. However, the biological role of PART1 in the chemoresistance of OC is still unclear. In this study, it was found that the expression levels of PART1 and CHRAC1 were increased and miR-512-3p expression was decreased in cisplatin (DDP)-resistant OC cell lines. The depletion of PART1 enhanced the DDP sensitivity of DDP-resistant OC cells, as indicated by the inhibition of cell proliferation, migration, and invasion, and promotion of cell apoptosis. In the upstream mechanism exploration, we discovered that PART1 was induced by YY1 transcription factor. Moreover, it was identified that miR-512-3p was a target of PART1, and PART1 regulated the DDP resistance of OC through miR-512-3p. In addition, we screened the candidate genes of miR-512-3p., and confirmed that CHRAC1 was the downstream gene of miR-512-3p. Furthermore, the knockdown of CHRAC1 inhibited proliferation, migration, and invasion, and accelerated apoptosis of DDP-resistant OC cells, which was counteracted after the inhibition of miR-512-3p. Finally, we observed that PART1 regulated the expression of CHRAC1 through miR-512-3p. In conclusion, we demonstrated that YY1-induced PART1 accelerated DDP resistance of OC through miR-512-3p/CHRAC1 axis, suggesting PART1 may be a promising therapeutic target for DDP-resistant OC patients.
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Affiliation(s)
- Hongbo Yang
- Department of Gynecology, Huai'an Maternity and Child Care Hospital, Huai'an, Jiangsu, China
| | - Xuegang Zhang
- Department of Gynecology, the First People's Hospital of Kunshan, Suzhou, Jiangsu, China
| | - Li Zhu
- Department of Gynecology, the Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Yang Yang
- Department of Gynecology, the Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Xinming Yin
- Department of Gynecology, the Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
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26
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Lv T, Liu H, Wu Y, Huang W. Knockdown of lncRNA DLEU1 inhibits the tumorigenesis of oral squamous cell carcinoma via regulation of miR‑149‑5p/CDK6 axis. Mol Med Rep 2021; 23:447. [PMID: 33880596 PMCID: PMC8060799 DOI: 10.3892/mmr.2021.12086] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 02/03/2021] [Indexed: 12/13/2022] Open
Abstract
Oral squamous cell carcinoma (OSCC) is a frequent malignant tumor worldwide. Long non-coding RNAs (lncRNAs) are known to play key roles in different types of cancer, including OSCC. It was previously reported that lncRNA deleted in lymphocytic leukemia 1 (DLEU1) is notably upregulated in OSCC; however, the role of DLEU1 in OSCC remains unclear. Gene and protein expression levels in OSCC cells were detected by reverse transcription-quantitative PCR and western blotting, respectively, in the present study. A Transwell assay was performed to measure cell migration and invasion. Flow cytometry was used to detect cell apoptosis, and the dual-luciferase reporter assay was applied to confirm the interaction between DLEU1, microRNA (miR)-149-5p and CDK6 in OSCC cells. DLEU1 expression was negatively associated with the survival rate of patients with OSCC. In addition, silencing of DLEU1 notably inhibited the proliferation of OSCC cells by inducing apoptosis. Meanwhile, DLEU1 directly bound to miR-149-5p, and CDK6 was found to be the direct target of miR-149-5p. Furthermore, DLEU1 knockdown-induced inhibition of OSCC cell proliferation was significantly reversed by the miR-149-5p antagomir. Knockdown of lncRNA DLEU1 reversed the proliferation of OSCC cells via regulation of the miR-149-5p/CDK6 axis. Thus, DLEU1 may serve as a novel target for treating OSCC.
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Affiliation(s)
- Tianzhu Lv
- Department of Emergency General, The Affiliated Stomatological Hospital of Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China
| | - Hongjing Liu
- Department of Emergency General, The Affiliated Stomatological Hospital of Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China
| | - Yadong Wu
- Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China
| | - Wentao Huang
- Department of Basic Stomatology, School of Savaid Stomatology, Hangzhou Medical College, Hangzhou, Zhejiang 310053, P.R. China
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27
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Zhang L, Ma T, Tao Q, Tan W, Chen H, Liu W, Lin P, Zhou D, Wang A, Jin Y, Tang K. Bta-miR-34b inhibits proliferation and promotes apoptosis via the MEK/ERK pathway by targeting MAP2K1 in bovine primary Sertoli cells. J Anim Sci 2021; 98:5909278. [PMID: 32954430 DOI: 10.1093/jas/skaa313] [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] [Received: 07/15/2020] [Accepted: 09/18/2020] [Indexed: 12/14/2022] Open
Abstract
Immature Sertoli cell (SC) proliferation determines the final number of mature SCs and further regulates spermatogenesis. Accumulating evidence demonstrated that microRNAs (miRNAs) play an important role in SC proliferation, differentiation, and apoptosis. However, the effect and molecular mechanism of miRNA on bovine immature SC remain to be poorly understood. In this study, miRNA sequencing of testes collected in mature (24-mo old) and immature (neonatal) bulls was conducted to determine the miRNA expression profiles. MicroRNA-34b was one of the differentially expressed miRNAs and was selected for in-depth functional studies pertaining to SC growth. The results showed that miR-34b mimic transfection in primary Sertoli cells (PSC) inhibited cell proliferation and induced cell cycle arrested at G2 phase and decreased the expression of cell cycle-related genes such as CCNB1, CDK1, CDC25C, and C-MYC. MicroRNA-34b overexpression also leads to increased cell apoptosis, with proapoptotic genes P53 and BAX upregulated, while antiapoptotic gene BCL2 decreased. However, miR-34b knockdown had the opposite effects. Through a combination of transcriptome sequencing, bioinformatics analysis, dual-luciferase reporter assay, and Western blotting, mitogen-activated protein kinase kinase1 (MAP2K1), also known as MEK1, was identified as a target of miR-34b. In addition, PSC proliferation inhibition was mediated by cell cycle arrest and apoptosis with MAP2K1 interference. Overexpression of MAP2K1 effectively reversed the miR-34b-repressed PSC cell growth. Moreover, both miR-34b overexpression and MAP2K1 knockdown decreased the protein levels of P-ERK1/2, while MAP2K1 overexpression showed opposite effects. In summary, data suggest that miR-34b regulates PSC proliferation and apoptosis through the MEK/ERK signaling pathway. These data provide a theoretical and experimental framework for further clarifying the regulation of cell growth in PSC of bovine.
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Affiliation(s)
- Linlin Zhang
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.,Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China
| | - Tiantian Ma
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.,Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China
| | - Qibing Tao
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.,Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China
| | - Wushuang Tan
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
| | - Huatao Chen
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.,Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China
| | - Wei Liu
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.,Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China
| | - Pengfei Lin
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.,Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China
| | - Dong Zhou
- Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China.,Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
| | - Aihua Wang
- Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China.,Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
| | - Yaping Jin
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.,Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China
| | - Keqiong Tang
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.,Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China
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28
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Pu J, Tan C, Shao Z, Wu X, Zhang Y, Xu Z, Wang J, Tang Q, Wei H. Long Noncoding RNA PART1 Promotes Hepatocellular Carcinoma Progression via Targeting miR-590-3p/ HMGB2 Axis. Onco Targets Ther 2020; 13:9203-9211. [PMID: 32982307 PMCID: PMC7502387 DOI: 10.2147/ott.s259962] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 08/03/2020] [Indexed: 12/24/2022] Open
Abstract
Introduction In East Asia, hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancer types. Long noncoding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) was reported to play crucial roles in regulating cancer progression. However, roles and mechanisms of action of PART1 in hepatocellular carcinoma (HCC) still remain unknown. Methods Quantitative real-time polymerase chain reaction (RT-qPCR) method was used to detect the PART1 expression level in HCC cells. Cell proliferation, colony formation, and transwell invasion assays were performed to investigate the biological roles of PART1 on HCC cell behaviors. Bioinformatic analysis methods were performed to analyze connections of microRNA-590-3p (miR-590-3p) with PART1 or high mobility group box 2 (HMGB2) in HCC. Moreover, expression levels of PART1, miR-590-3p, and HMGB2 in HCC tissues and normal tissues were analyzed at ENCORI. Results PART1 expression was found to be significantly upregulated in HCC tissues and cells. Functionally, silencing of PART1 significantly suppressed HCC cell proliferation, colony formation and invasion in vitro, while forcing PART1 exerts opposite biological effects. Mechanically, miR-590-3p/HMGB2 axis was downstream target of PART1, and silencing of miR-590-3p or forcing of HMGB2 could rescue the stimulation effects of PART1 overexpression on HCC cell behaviors. Discussion Our results provided evidence that PART1 serves as oncogenic lncRNA through sponging miR-590-3p to upregulate HMGB2 expression in HCC.
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Affiliation(s)
- Jian Pu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, People's Republic of China
| | - Chuan Tan
- Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, People's Republic of China
| | - Zesheng Shao
- Graduate College, Youjiang Medical University for Nationalities, Baise, Guangxi, People's Republic of China
| | - Xianjian Wu
- Graduate College, Youjiang Medical University for Nationalities, Baise, Guangxi, People's Republic of China
| | - Ya Zhang
- Graduate College, Youjiang Medical University for Nationalities, Baise, Guangxi, People's Republic of China
| | - Zuoming Xu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, People's Republic of China
| | - Jianchu Wang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, People's Republic of China
| | - Qianli Tang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, People's Republic of China
| | - Huamei Wei
- Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, People's Republic of China
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Cao L, Qin P, Zhang J, Qiao H, Shi P, Huo H. LncRNA PVT1 Suppresses the Progression of Renal Fibrosis via Inactivation of TGF-β Signaling Pathway. Drug Des Devel Ther 2020; 14:3547-3557. [PMID: 32921988 PMCID: PMC7457787 DOI: 10.2147/dddt.s245244] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Accepted: 07/31/2020] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Renal fibrosis is a frequent pathway leading to end-stage kidney dysfunction. In addition, renal fibrosis is the ultimate manifestation of chronic kidney diseases (CKD). Long noncoding RNAs (lncRNAs) are known to be involved in occurrence of renal fibrosis, and lncRNA plasmacytoma variant translocation 1 (PVT1) has been reported to act as a key biomarker in renal diseases. However, the role of PVT1 in renal fibrosis remains unclear. MATERIALS AND METHODS HK-2 cells were treated with TGF-β1 to mimic renal fibrosis in vitro. Gene and protein expressions in HK-2 cells were measured by qRT-PCR and Western-blot, respectively. ELISA was used to test the level of creatinine (CR) and blood urea nitrogen (BUN) in serum of mice. Additionally, unilateral ureteral obstruction (UUO)-induced renal fibrosis mice model was established to investigate the effect of PVT1 on renal fibrosis in vivo. RESULTS PVT1 was upregulated in TGF-β1-treated HK-2 cells. In addition, TGF-β1-induced upregulation of α-SMA and fibronectin in HK-2 cells was significantly reversed by PVT1 knockdown. Meanwhile, PVT1 bound to miR-181a-5p in HK-2 cells. Moreover, miR-181a-5p directly targeted TGF-βR1. Furthermore, miR-181a-5p antagonist could significantly reverse the anti-fibrotic effect of PVT1 knockdown. Besides, knockdown of PVT1 notably attenuated the symptom of renal fibrosis in vivo. CONCLUSION Knockdown of PVT1 significantly inhibited the progression of renal fibrosis in vitro and in vivo. Thus, PVT1 may serve as a potential target for the treatment of renal fibrosis.
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Affiliation(s)
- Lu Cao
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan450000, People’s Republic of China
| | - Peng Qin
- Department of Cancer Immunotherapy, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan450000, People’s Republic of China
| | - Jianjiang Zhang
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan450000, People’s Republic of China
| | - Huiju Qiao
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan450000, People’s Republic of China
| | - Peipei Shi
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan450000, People’s Republic of China
| | - Huali Huo
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan450000, People’s Republic of China
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Chen X, Li X, Peng X, Zhang C, Liu K, Huang G, Lai Y. Use of a Four-miRNA Panel as a Biomarker for the Diagnosis of Stomach Adenocarcinoma. DISEASE MARKERS 2020; 2020:8880937. [PMID: 33224315 PMCID: PMC7670587 DOI: 10.1155/2020/8880937] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 10/18/2020] [Accepted: 10/27/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND MicroRNAs (miRNAs) have been applied to cancer diagnosis taking into account their role in tumorigenesis. The main purpose of our study was to confirm the possibility of using miRNAs as noninvasive biomarkers for stomach adenocarcinoma (STAD) diagnosis. METHODS A total of 246 participants (130 STAD patients and 116 healthy controls (HCs)) were enrolled in this 3-phase study. Five STAD pools and 3 HC pools (with 4 participants in each pool) were used for the screening of the 28 miRNAs using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The training phase (30 STAD patients vs. 24 HCs) and validation phase (80 STAD patients vs. 80 HCs) were used to further verify the identity of these miRNAs. Kaplan-Meier survival analysis and bioinformatics analysis were also used. RESULTS The expression levels of miR-125b-5p and miR-196a-5p were upregulated in STAD serum, compared with the HCs, while miR-1-3p and miR-149-5p showed the opposite result. A four-serum miRNA panel was constructed, and the area under the receiver operating characteristic curve (AUC) was found to be 0.892 (95% CI: 0.834 to 0.936, sensitivity = 86.25%, specificity = 78.75%). Only miR-125b-5p expression showed a significant difference between STAD patients and NCs in the survival analysis. The neurotrophin signaling pathway was associated with 4 miRNAs identified in STAD patients. CONCLUSION The four-serum miRNA panel has great potential to be used as a noninvasive biomarker for STAD diagnosis.
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Affiliation(s)
- Xuan Chen
- Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, China
- Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Xinji Li
- Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, China
- Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Xiqi Peng
- Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, China
- Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Chunduo Zhang
- Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, China
| | - Kaihao Liu
- Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, China
- Anhui Medical University, Hefei, Anhui 230032, China
| | - Guocheng Huang
- Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, China
- Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Yongqing Lai
- Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, China
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