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Cheng G, Chen F, Li S, Hu Y, Dai Z, Hu Z, Gan Z, Sun Y, Zheng X. Precise design of dual active-site catalysts for synergistic catalytic therapy of tumors. J Mater Chem B 2024; 12:1512-1522. [PMID: 38251988 DOI: 10.1039/d3tb02145a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2024]
Abstract
A proven and promising method to improve the catalytic performance of single-atom catalysts through the interaction between bimetallic atoms to change the active surface sites or adjust the catalytic sites of reactants is reported. In this work, we used an iron-platinum bimetallic reagent as the metal source to precisely synthesise covalent organic framework-derived diatomic catalysts (FePt-DAC/NC). Benefiting from the coordination between the two metal atoms, the presence of Pt single atoms can successfully regulate Fe-N3 activity. FePt-DAC/NC exhibited a stronger ability to catalyze H2O2 to produce toxic hydroxyl radicals than Fe single-atom catalysts (Fe-SA/NC) to achieve chemodynamic therapy of tumors (the catalytic efficiency improved by 186.4%). At the same time, under the irradiation of an 808 nm laser, FePt-DAC/NC exhibited efficient photothermal conversion efficiency to achieve photothermal therapy of tumors. Both in vitro and in vivo results indicate that FePt-DAC/NC can efficiently suppress tumor cell growth by a synergistic therapeutic effect with photothermally augmented nanocatalytic therapy. This novel bimetallic dual active-site monodisperse catalyst provides an important example for the application of single-atom catalysts in the biomedical field, highlighting its promising clinical potential.
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Affiliation(s)
- Guodong Cheng
- College of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, P. R. China.
- Key Laboratory of Functional Nanomaterials and Technology in Universities of Shandong, Linyi University, Linyi 276000, P. R. China.
- Qilu Normal University, Jinan, 250013, P. R. China
| | - Fuying Chen
- College of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, P. R. China.
- Key Laboratory of Functional Nanomaterials and Technology in Universities of Shandong, Linyi University, Linyi 276000, P. R. China.
| | - Shulian Li
- Linyi Cancer Hospital, Linyi, 272067, P. R. China
| | - Yu Hu
- Zhucheng City People's Hospital, Zhucheng, 262200, P. R. China
| | - Zhichao Dai
- College of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, P. R. China.
- Key Laboratory of Functional Nanomaterials and Technology in Universities of Shandong, Linyi University, Linyi 276000, P. R. China.
| | - Zunfu Hu
- College of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, P. R. China.
- Key Laboratory of Functional Nanomaterials and Technology in Universities of Shandong, Linyi University, Linyi 276000, P. R. China.
| | - Zibao Gan
- College of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, P. R. China.
- Key Laboratory of Functional Nanomaterials and Technology in Universities of Shandong, Linyi University, Linyi 276000, P. R. China.
| | - Yunqiang Sun
- College of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, P. R. China.
- Key Laboratory of Functional Nanomaterials and Technology in Universities of Shandong, Linyi University, Linyi 276000, P. R. China.
| | - Xiuwen Zheng
- Key Laboratory of Functional Nanomaterials and Technology in Universities of Shandong, Linyi University, Linyi 276000, P. R. China.
- Qilu Normal University, Jinan, 250013, P. R. China
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2
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Expression and function of FRA1 protein in tumors. Mol Biol Rep 2019; 47:737-752. [PMID: 31612408 DOI: 10.1007/s11033-019-05123-9] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Accepted: 10/09/2019] [Indexed: 12/24/2022]
Abstract
AP-1 is a dimeric complex that is composed of JUN, FOS, ATF and MAF protein families. FOS-related antigen 1 (FRA1) which encoded by FOSL1 gene, belongs to the FOS protein family, and mainly forms an AP-1 complex with the protein of the JUN family to exert an effect. Regulation of FRA1 occurs at levels of transcription and post-translational modification, and phosphorylation is the major post-translational modification. FRA1 is mainly regulated by the mitogen-activated protein kinases signaling pathway and is degraded by ubiquitin-independent proteasomes. FRA1 can affect biological functions, such as tumor proliferation, differentiation, invasion and apoptosis. Studies have demonstrated that FRA1 is abnormally expressed in many tumors and plays a relevant role, but the specific condition varies from the target organs. FRA1 is overexpressed in breast cancer, lung cancer, colorectal cancer, prostate cancer, nasopharyngeal cancer, thyroid cancer and other tumors. However, the expression of FRA1 is decreased in cervical cancer, and the expression of FRA1 in ovarian cancer and oral squamous cell carcinoma is still controversial. In this review, we present a detailed description of the regulatory factors and functions of FRA1, also, the expression of FRA1 in various tumors and its function in relative tumor.
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Organista-Nava J, Gómez-Gómez Y, Garibay-Cerdenares OL, Leyva-Vázquez MA, Illades-Aguiar B. Cervical cancer stem cell-associated genes: Prognostic implications in cervical cancer. Oncol Lett 2019; 18:7-14. [PMID: 31289465 PMCID: PMC6540231 DOI: 10.3892/ol.2019.10307] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 03/18/2019] [Indexed: 12/14/2022] Open
Abstract
Cervical cancer is the fourth most common type of gynecological malignancy to affect females, worldwide. Although high-risk human papillomavirus (HR-HPV) infection is the primary etiologic agent associated with the development of cervical cancer, cancer stem cells (CSCs) also serve a prominent role in the development, metastasis, recurrence and prognosis of the disease. CSCs are a small subpopulation of cells that have the ability to self-renew and are present in the majority of tumors, including cervical cancer. Studies describing the phenotype of cervical CSCs (CCSCs) vary in their definition of the expression pattern of principal biomarkers, including Musashi-1, aldehyde dehydrogenase 1, Oct3/4, Sox2 and CD49f. However, these markers are not observed in all cancers, although several may be present in multiple tumor types. The present review describes the potential biomarkers of CSCs in cervical cancer. These CCSC biomarkers may serve as molecular targets to enhance the efficacy and reduce the side effects associated with chemotherapeutic treatment in HR-HPV-positive cervical cancer.
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Affiliation(s)
- Jorge Organista-Nava
- Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero 39090, Mexico
| | - Yazmín Gómez-Gómez
- Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero 39090, Mexico
| | - Olga Lilia Garibay-Cerdenares
- Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero 39090, Mexico.,Consejo Nacional de Ciencia y Tecnología, Mexico City 03940, Mexico
| | - Marco Antonio Leyva-Vázquez
- Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero 39090, Mexico
| | - Berenice Illades-Aguiar
- Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero 39090, Mexico
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4
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Chokchaichamnankit D, Watcharatanyatip K, Subhasitanont P, Weeraphan C, Keeratichamroen S, Sritana N, Kantathavorn N, Diskul-Na-Ayudthaya P, Saharat K, Chantaraamporn J, Verathamjamras C, Phoolcharoen N, Wiriyaukaradecha K, Paricharttanakul NM, Udomchaiprasertkul W, Sricharunrat T, Auewarakul C, Svasti J, Srisomsap C. Urinary biomarkers for the diagnosis of cervical cancer by quantitative label-free mass spectrometry analysis. Oncol Lett 2019; 17:5453-5468. [PMID: 31186765 PMCID: PMC6507435 DOI: 10.3892/ol.2019.10227] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Accepted: 03/27/2019] [Indexed: 12/15/2022] Open
Abstract
Due to the invasive procedure associated with Pap smears for diagnosing cervical cancer and the conservative culture of developing countries, identifying less invasive biomarkers is of great interest. Quantitative label-free mass spectrometry was performed to identify potential biomarkers in the urine samples of patients with cervical cancer. This technique was used to study the differential expression of urinary proteomes between normal individuals and cancer patients. The alterations in the levels of urinary proteomes in normal and cancer patients were analyzed by Progenesis label-free software and the results revealed that 60 proteins were upregulated while 73 proteins were downregulated in patients with cervical cancer. This method could enrich high molecular weight proteins from 100 kDa. The protein-protein interactions were obtained by Search Tool for the Retrieval of Interacting Genes/Proteins analysis and predicted the biological pathways involving various functions including cell-cell adhesion, blood coagulation, metabolic processes, stress response and the regulation of morphogenesis. Two notable upregulated urinary proteins were leucine-rich α-2-glycoprotein (LRG1) and isoform-1 of multimerin-1 (MMRN1), while the 3 notable downregulated proteins were S100 calcium-binding protein A8 (S100A8), serpin B3 (SERPINB3) and cluster of differentiation-44 antigen (CD44). The validation of these 5 proteins was performed by western blot analysis and the biomarker sensitivity of these proteins was analyzed individually and in combination with receiver operator characteristic curve (ROC) analysis. Quantitative mass spectrometry analysis may allow for the identification of urinary proteins of high molecular weight. The proteins MMRN1 and LRG1 were presented, for the first time, to be highly expressed urinary proteins in cervical cancer. ROC analysis revealed that LRG1 and SERPINB3 could be individually used, and these 5 proteins could also be combined, to detect the occurrence of cervical cancer.
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Affiliation(s)
| | | | | | - Churat Weeraphan
- Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand.,Department of Molecular Biotechnology and Bioinformatics Faculty of Science, Prince of Songkla University, Songkla 90110, Thailand
| | | | - Narongrit Sritana
- Molecular and Genomic Research Laboratory, Research and International Relations Division, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok 10210, Thailand
| | - Nuttavut Kantathavorn
- Gynecologic Oncology Unit, Woman Health Center, Chulabhorn Royal Academy, Bangkok 10210, Thailand
| | | | - Kittirat Saharat
- Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand
| | | | - Chris Verathamjamras
- Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand
| | - Natacha Phoolcharoen
- Gynecologic Oncology Unit, Woman Health Center, Chulabhorn Royal Academy, Bangkok 10210, Thailand
| | - Kriangpol Wiriyaukaradecha
- Molecular and Genomic Research Laboratory, Research and International Relations Division, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok 10210, Thailand
| | | | - Wandee Udomchaiprasertkul
- Molecular and Genomic Research Laboratory, Research and International Relations Division, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok 10210, Thailand
| | - Thaniya Sricharunrat
- Pathology Laboratory Unit, Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok 10210, Thailand
| | - Chirayu Auewarakul
- Research and International Relations Division, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok 10210, Thailand.,Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Jisnuson Svasti
- Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand.,Applied Biological Sciences Program, Chulabhorn Graduate Institute, Bangkok 10210, Thailand
| | - Chantragan Srisomsap
- Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand
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5
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Sakaram S, Craig MP, Hill NT, Aljagthmi A, Garrido C, Paliy O, Bottomley M, Raymer M, Kadakia MP. Identification of novel ΔNp63α-regulated miRNAs using an optimized small RNA-Seq analysis pipeline. Sci Rep 2018; 8:10069. [PMID: 29968742 PMCID: PMC6030203 DOI: 10.1038/s41598-018-28168-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 06/15/2018] [Indexed: 12/29/2022] Open
Abstract
Advances in high-throughput sequencing have enabled profiling of microRNAs (miRNAs), however, a consensus pipeline for sequencing of small RNAs has not been established. We built and optimized an analysis pipeline using Partek Flow, circumventing the need for analyzing data via scripting languages. Our analysis assessed the effect of alignment reference, normalization method, and statistical model choice on biological data. The pipeline was evaluated using sequencing data from HaCaT cells transfected with either a non-silencing control or siRNA against ΔNp63α, a p53 family member protein which is highly expressed in non-melanoma skin cancer and shown to regulate a number of miRNAs. We posit that 1) alignment and quantification to the miRBase reference provides the most robust quantitation of miRNAs, 2) normalizing sample reads via Trimmed Mean of M-values is the most robust method for accurate downstream analyses, and 3) use of the lognormal with shrinkage statistical model effectively identifies differentially expressed miRNAs. Using our pipeline, we identified previously unrecognized regulation of miRs-149-5p, 18a-5p, 19b-1-5p, 20a-5p, 590-5p, 744-5p and 93-5p by ΔNp63α. Regulation of these miRNAs was validated by RT-qPCR, substantiating our small RNA-Seq pipeline. Further analysis of these miRNAs may provide insight into ΔNp63α's role in cancer progression. By defining the optimal alignment reference, normalization method, and statistical model for analysis of miRNA sequencing data, we have established an analysis pipeline that may be carried out in Partek Flow or at the command line. In this manner, our pipeline circumvents some of the major hurdles encountered during small RNA-Seq analysis.
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Affiliation(s)
- Suraj Sakaram
- Biochemistry and Molecular Biology, Wright State University, Dayton, OH, 45435, USA
| | - Michael P Craig
- Biochemistry and Molecular Biology, Wright State University, Dayton, OH, 45435, USA
| | - Natasha T Hill
- Biochemistry and Molecular Biology, Wright State University, Dayton, OH, 45435, USA
| | - Amjad Aljagthmi
- Biochemistry and Molecular Biology, Wright State University, Dayton, OH, 45435, USA
| | - Christian Garrido
- Biochemistry and Molecular Biology, Wright State University, Dayton, OH, 45435, USA
| | - Oleg Paliy
- Biochemistry and Molecular Biology, Wright State University, Dayton, OH, 45435, USA
| | - Michael Bottomley
- Math and Microbiology, Wright State University, Dayton, OH, 45435, USA
| | - Michael Raymer
- Computer Science and Engineering, Wright State University, Dayton, OH, 45435, USA
| | - Madhavi P Kadakia
- Biochemistry and Molecular Biology, Wright State University, Dayton, OH, 45435, USA.
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6
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Xiao S, Zhou Y, Yi W, Luo G, Jiang B, Tian Q, Li Y, Xue M. Fra-1 is downregulated in cervical cancer tissues and promotes cervical cancer cell apoptosis by p53 signaling pathway in vitro. Int J Oncol 2015; 46:1677-84. [PMID: 25651840 DOI: 10.3892/ijo.2015.2873] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2014] [Accepted: 01/22/2015] [Indexed: 11/05/2022] Open
Abstract
Cervical cancer is a potentially preventable disease; however, it is the third most commonly diagnosed cancer and the fourth leading cause of cancer deaths in women worldwide. Cervical cancer is thought to develop through a multistep process involving virus, tumor suppressor genes, proto-oncogenes and immunological factors. It is known that human papillomavirus (HPV) infection is necessary but insufficient to cause malignancy. At present, the etiology of cervical carcinoma remains poorly understood. In this study, we found that the expression of FOS-like antigen-1 (Fra-1) gene was downregulated in cervical cancer compared with the adjacent non-cancerous tissues by RT-qPCR, immunohistochemistry (IHC) and western blotting techniques. To uncover the effect of Fra-1 on cervical cancer, we tested and confirmed that Fra-1 significantly inhibited the proliferation of HeLa cells by MMT assays in vitro. At the same time, overexpression of Fra-1 promoted apoptosis of HeLa cells. To explore the possible mechanism of Fra-1 in cervical cancer, we tested the expression levels of key molecules in p53 signaling pathway by western blotting technology. The results showed that p53 was downregulated in cervical cancer compared with the adjacent non-cancerous tissues, but MDM2 proto-oncogene, E3 ubiquitin protein ligase (MDM2) was upregulated in cervical cancer. In vitro, the p53 was upregulated and MDM2 was downregulated in HeLa cells with Fra-1 overexpression. In summary, our results suggested that Fra-1 expression is low in cervical cancer tissues and promotes apoptosis of cervical cancer cells by p53 signaling pathway.
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Affiliation(s)
- Songshu Xiao
- Department of Gynecology and Obstetrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China
| | - Yanhong Zhou
- Cancer Research Institute, Central South University, Changsha, Hunan 410078, P.R. China
| | - Wei Yi
- Cancer Research Institute, Central South University, Changsha, Hunan 410078, P.R. China
| | - Guijuan Luo
- Department of Gynecology and Obstetrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China
| | - Bin Jiang
- Department of Gynecology and Obstetrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China
| | - Qi Tian
- Department of Gynecology and Obstetrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China
| | - Yueran Li
- Department of Gynecology and Obstetrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China
| | - Min Xue
- Department of Gynecology and Obstetrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China
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7
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Niu ZS, Niu XJ, Wang M. Management of hepatocellular carcinoma: Predictive value of immunohistochemical markers for postoperative survival. World J Hepatol 2015; 7:7-27. [PMID: 25624992 PMCID: PMC4295195 DOI: 10.4254/wjh.v7.i1.7] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2014] [Revised: 09/02/2014] [Accepted: 11/07/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) accounts for over 90% of all primary liver cancers. With an ever increasing incidence trend year by year, it has become the third most common cause of death from cancer worldwide. Hepatic resection is generally considered to be one of the most effective therapies for HCC patients, however, there is a high risk of recurrence in postoperative HCC. In clinical practice, there exists an urgent need for valid prognostic markers to identify patients with prognosis, hence the importance of studies on prognostic markers in improving the prediction of HCC prognosis. This review focuses on the most promising immunohistochemical prognostic markers in predicting the postoperative survival of HCC patients.
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Affiliation(s)
- Zhao-Shan Niu
- Zhao-Shan Niu, Lab of Micromorphology, Medical College of Qingdao University, Qingdao 266071, Shandong Province, China
| | - Xiao-Jun Niu
- Zhao-Shan Niu, Lab of Micromorphology, Medical College of Qingdao University, Qingdao 266071, Shandong Province, China
| | - Mei Wang
- Zhao-Shan Niu, Lab of Micromorphology, Medical College of Qingdao University, Qingdao 266071, Shandong Province, China
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8
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Liao S, Xiao S, Zhu G, Zheng D, He J, Pei Z, Li G, Zhou Y. CD38 is highly expressed and affects the PI3K/Akt signaling pathway in cervical cancer. Oncol Rep 2014; 32:2703-9. [PMID: 25310288 DOI: 10.3892/or.2014.3537] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2014] [Accepted: 09/02/2014] [Indexed: 11/06/2022] Open
Abstract
Cervical cancer is the second most common cancer and the fifth most deadly malignancy in females worldwide, affecting 500,000 individuals each year. It is the leading cause of cancer mortality among women in developing countries. Dysregulated activation of genes, such as CD44, SOX9 and SKP2, plays a role in cervical cancer. CD38 is known to be involved in activities typical of cell surface receptors, such as signaling for activation and proliferation events and heterotypic cell adhesion. CD38 contributes to disease progression and relapse in certain tumors, such as acute myeloid and chronic lymphocytic leukemia. To the best of our knowledge, there is currently no report on the relationship between CD38 and cervical cancer. Using qPCR, immunohistochemistry, and western blot analysis, the expression levels of CD38 were investigated and found to be upregulated in cervical cancer. CD38 was correlated with dysregulation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway in cervical cancer tissues in vitro. At the same time, CD38 overexpression affected the expression of PI3K, Akt, MDM2 and p53 in vivo. The results of the present study suggested that CD38 is highly expressed in cervical carcinoma tissues and play an important role in dysregulation of the PI3K/Akt signaling pathway.
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Affiliation(s)
- Shan Liao
- Hunan Provincial Tumor Hospital and The Tumor Hospital Affiliated to Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China
| | - Songshu Xiao
- Department of Gynecology and Obstetrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China
| | - Guangchao Zhu
- Hunan Provincial Tumor Hospital and The Tumor Hospital Affiliated to Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China
| | - Danwei Zheng
- Hunan Provincial Tumor Hospital and The Tumor Hospital Affiliated to Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China
| | - Junyu He
- Hunan Provincial Tumor Hospital and The Tumor Hospital Affiliated to Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China
| | - Zhen Pei
- Hunan Provincial Tumor Hospital and The Tumor Hospital Affiliated to Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China
| | - Guiyuan Li
- Hunan Provincial Tumor Hospital and The Tumor Hospital Affiliated to Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China
| | - Yanhong Zhou
- Hunan Provincial Tumor Hospital and The Tumor Hospital Affiliated to Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China
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