Tumor suppressive microRNA-200a inhibits renal cell carcinoma development by directly targeting TGFB2

详细信息    查看全文

• 作者：Ruijing Lu ; Ziliang Ji ; Xiaoqing Li ; Jie Qin ; Guanghui Cui ; Jing Chen…
• 关键词：miR ; 200a ; Tumor suppressor ; TGFB2 ; Renal cell carcinoma
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：36
• 期：9
• 页码：6691-6700
• 全文大小：9,039 KB
• 参考文献：1.Rini BI, Campbell SC, Escudier B. Renal cell carcinoma. Lancet. 2009;373(9669):1119–32.PubMed CrossRef
  2.Campbell SC, Flanigan RC, Clark JI. Nephrectomy in metastatic renal cell carcinoma. Curr Treat Options Oncol. 2003;4(5):363–72.PubMed CrossRef
  3.Sun M, Lughezzani G, Perrotte P, Karakiewicz PI. Treatment of metastatic renal cell carcinoma. Nat Rev Urol. 2010;7(6):327–38.PubMed CrossRef
  4.Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.PubMed CrossRef
  5.Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 2007;129(7):1401–14.PubMed PubMedCentral CrossRef
  6.Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259–69.PubMed CrossRef
  7.Nakada C, Matsuura K, Tsukamoto Y, Tanigawa M, Yoshimoto T, Narimatsu T, et al. Genome‐wide microRNA expression profiling in renal cell carcinoma: significant down‐regulation of miR‐141 and miR‐200c. J Pathol. 2008;216(4):418–27.PubMed CrossRef
  8.White N, Khella H, Grigull J, Adzovic S, Youssef Y, Honey R, et al. miRNA profiling in metastatic renal cell carcinoma reveals a tumour-suppressor effect for miR-215. Br J Cancer. 2011;105(11):1741–9.PubMed PubMedCentral CrossRef
  9.Hidaka H, Seki N, Yoshino H, Yamasaki T, Yamada Y, Nohata N, et al. Tumor suppressive microRNA-1285 regulates novel molecular targets: aberrant expression and functional significance in renal cell carcinoma. Oncotarget. 2012;3(1):44.PubMed PubMedCentral CrossRef
  10.Zhou L, Chen J, Li Z, Li X, Hu X, Huang Y, et al. Integrated profiling of microRNAs and mRNAs: microRNAs located on Xq27.3 associate with clear cell renal cell carcinoma. PLoS One. 2010;5(12):e15224.PubMed PubMedCentral CrossRef
  11.Mongroo PS, Rustgi AK. The role of the miR-200 family in epithelial-mesenchymal transition. Cancer Biol Ther. 2010;10(3):219–22.PubMed PubMedCentral CrossRef
  12.Xia H, Ng SS, Jiang S, Cheung WK, Sze J, Bian X-W, et al. miR-200a-mediated downregulation of ZEB2 and CTNNB1 differentially inhibits nasopharyngeal carcinoma cell growth, migration and invasion. Biochem Biophys Res Commun. 2010;391(1):535–41.PubMed CrossRef
  13.Feng J, Wang J, Chen M, Chen G, Wu Z, Ying L, et al. miR-200a suppresses cell growth and migration by targeting MACC1 and predicts prognosis in hepatocellular carcinoma. Oncol Rep. 2015;33(2):713–20.PubMed
  14.Barron N, Keenan J, Gammell P, Martinez VG, Freeman A, Masters JR, et al. Biochemical relapse following radical prostatectomy and miR‐200a levels in prostate cancer. Prostate. 2012;72(11):1193–9.PubMed CrossRef
  15.Hu X, Macdonald DM, Huettner PC, Feng Z, El Naqa IM, Schwarz JK, et al. A miR-200 microRNA cluster as prognostic marker in advanced ovarian cancer. Gynecol Oncol. 2009;114(3):457–64.PubMed CrossRef
  16.Yoshino H, Enokida H, Itesako T, Tatarano S, Kinoshita T, Fuse M, et al. Epithelial-mesenchymal transition-related microRNA-200s regulate molecular targets and pathways in renal cell carcinoma. J Hum Genet. 2013;58(8):508–16.PubMed CrossRef
  17.Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 1982;6(7):655–64.PubMed CrossRef
  18.Lu R, Ji Z, Li X, Zhai Q, Zhao C, Jiang Z, et al. miR-145 functions as tumor suppressor and targets two oncogenes, ANGPT2 and NEDD9, in renal cell carcinoma. J Cancer Res Clin. 2014;140(3):387–97.CrossRef
  19.Zhai Q, Zhou L, Zhao C, Wan J, Yu Z, Guo X, et al. Identification of miR-508-3p and miR-509-3p that are associated with cell invasion and migration and involved in the apoptosis of renal cell carcinoma. Biochem Biophys Res Commun. 2012;419(4):621–6.PubMed CrossRef
  20.Korpal M, Kang Y. The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal transition and cancer metastasis. RNA Biol. 2008;5(3):115–9.PubMed PubMedCentral CrossRef
  21.Park S-M, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008;22(7):894–907.PubMed PubMedCentral CrossRef
  22.Korpal M, Lee ES, Hu G, Kang Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem. 2008;283(22):14910–4.PubMed PubMedCentral CrossRef
  23.Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10(5):593–601.PubMed CrossRef
  24.Becker LE, Takwi AAL, Lu Z, Li Y. The role of miR-200a in mammalian epithelial cell transformation. Carcinogenesis. 2014;36(1):2–12.PubMed PubMedCentral CrossRef
  25.Saydam O, Shen Y, Würdinger T, Senol O, Boke E, James MF, et al. Downregulated microRNA-200a in meningiomas promotes tumor growth by reducing E-cadherin and activating the Wnt/β-catenin signaling pathway. Mol Cell Biol. 2009;29(21):5923–40.PubMed PubMedCentral CrossRef
  26.Eades G, Yao Y, Yang M, Zhang Y, Chumsri S, Zhou Q. miR-200a regulates SIRT1 expression and epithelial to mesenchymal transition (EMT)-like transformation in mammary epithelial cells. J Biol Chem. 2011;286(29):25992–6002.PubMed PubMedCentral CrossRef
  27.Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119(6):1420.PubMed PubMedCentral CrossRef
  28.Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED, et al. Epithelial—mesenchymal and mesenchymal—epithelial transitions in carcinoma progression. J Cell Physiol. 2007;213(2):374–83.PubMed CrossRef
  29.Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis. Science. 2011;331(6024):1559–64.PubMed CrossRef
  30.Glasgow E, Mishra L. Transforming growth factor-β signaling and ubiquitinators in cancer. Endocr Relat Cancer. 2008;15(1):59–72.PubMed CrossRef
  31.Hill JJ, Tremblay T-L, Cantin C, O'Connor-McCourt M, Kelly JF, Lenferink A. Glycoproteomic analysis of two mouse mammary cell lines during transforming growth factor (TGF)-beta induced epithelial to mesenchymal transition. Proteome Sci. 2009;7(2):1–17.
  32.Sánchez-Capelo A. Dual role for TGF-β1 in apoptosis. Cytokine Growth Factor Rev. 2005;16(1):15–34.PubMed CrossRef
  33.Smith AL, Robin TP, Ford HL. Molecular pathways: targeting the TGF-β pathway for cancer therapy. Clin Cancer Res. 2012;18(17):4514–21.PubMed CrossRef
  34.Padua D, Massagué J. Roles of TGFβ in metastasis. Cell Res. 2008;19(1):89–102.CrossRef
  35.Epstein FH, Blobe GC, Schiemann WP, Lodish HF. Role of transforming growth factor β in human disease. N Engl J Med. 2000;342(18):1350–8.CrossRef
  36.Semczuk A, Zakrzewski P, Forma E, Cygankiewicz A, Semczuk-Sikora A, Bryś M, et al. TGFβ-pathway is down-regulated in a uterine carcinosarcoma: a case study. Pathol Res Pract. 2013;209(11):740–4.PubMed CrossRef
  37.Beisner J, Buck MB, Fritz P, Dippon J, Schwab M, Brauch H, et al. A novel functional polymorphism in the transforming growth factor-β2 gene promoter and tumor progression in breast cancer. Cancer Res. 2006;66(15):7554–61.PubMed CrossRef
  38.Wang B, Koh P, Winbanks C, Coughlan MT, McClelland A, Watson A, et al. miR-200a prevents renal fibrogenesis through repression of TGF-β2 expression. Diabetes. 2011;60:280–7.PubMed PubMedCentral CrossRef
  39.Xiong M, Jiang L, Zhou Y, Qiu W, Fang L, Tan R, et al. The miR-200 family regulates TGF-β1-induced renal tubular epithelial to mesenchymal transition through Smad pathway by targeting ZEB1 and ZEB2 expression. Am J Physiol Renal Physiol. 2012;302(3):F369–79.PubMed CrossRef
  40.Gregory PA, Bracken CP, Smith E, Bert AG, Wright JA, Roslan S, et al. An autocrine TGF-β/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition. Mol Biol Cell. 2011;22(10):1686–98.PubMed PubMedCentral CrossRef
  41.Bracken CP, Gregory PA, Kolesnikoff N, Bert AG, Wang J, Shannon MF, et al. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res. 2008;68(19):7846–54.PubMed CrossRef
  42.Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S, et al. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 2008;9(6):582–9.PubMed PubMedCentral CrossRef
  43.Gregory PA. An autocrine TGF-β/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition. Mol Biol Cell. 2011;22:1686–98.PubMed PubMedCentral CrossRef
  
• 作者单位：Ruijing Lu (1) (2)
  Ziliang Ji (3)
  Xiaoqing Li (1)
  Jie Qin (1)
  Guanghui Cui (1)
  Jing Chen (1)
  Qingna Zhai (1) (2)
  Chunjuan Zhao (1)
  Wei Zhang (4)
  Zhendong Yu (1)
  
  1. Central Laboratory, Peking University Shenzhen Hospital, Shenzhen, 518036, China
  2. Clinical Laboratory, Bao’an District of Shenzhen Maternity and Child Health Hospital, Shenzhen, 518133, China
  3. Department of Urology, Longgang District People’s Hospital of Shenzhen, Shenzhen, 518172, China
  4. Biomedical Research Institute, Shenzhen Peking University – the Hong Kong University of Science and Technology Medical Center, Shenzhen, 518036, China
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

A large body of evidence indicates that microRNAs play a critical role in tumor initiation and progression by negatively regulating oncogenes or tumor suppressor genes. Here, we report that the expression of miR-200a was notably downregulated in 45 renal cell carcinoma (RCC) samples. Restoration of miR-200a suppressed cell proliferation, migration, and invasion in two RCC cell lines. Furthermore, we used an epithelial-to-mesenchymal transition PCR array to explore the putative target genes of miR-200a. By performing quantitative real-time PCR, ELISA, and luciferase reporter assays, transforming growth factor beta2 (TGFB2) was validated as a direct target gene of miR-200a. Moreover, siRNA-mediated knockdown of TGFB2 partially phenocopied the effect of miR-200a overexpression. These results suggest that miR-200a suppresses RCC development via directly targeting TGFB2, indicating that miR-200a may present a novel target for diagnostic and therapeutic strategies in RCC.