Aberrant Expression of miR-20a and miR-203 in Cervical Cancer

  • Zhao, Shan (Department of Gynecologic Oncology, the Affiliated Tumor Hospital of Guangxi Medical University) ;
  • Yao, De-Sheng (Department of Gynecologic Oncology, the Affiliated Tumor Hospital of Guangxi Medical University) ;
  • Chen, Jun-Ying (Department of Gynecologic Oncology, the Affiliated Tumor Hospital of Guangxi Medical University) ;
  • Ding, Nan (Department of Gynecologic Oncology, the Affiliated Tumor Hospital of Guangxi Medical University)
  • 발행 : 2013.04.30


MicroRNAs (miRNAs) are small, non-coding RNAs that are critical regulators of various diseases. MicroRNA-20a (miR-20a) and microRNA-203 (miR-203) have previously shown significant alteration in a range of cancers. In this study, the expression levels of miR-20a and miR-203 in 100 cervical cancer tissues were detected by qRT-PCR and compared to patient matched-nontumor cervical tissues. Correlations between expression level and clinicopathologic characteristics of cervical cancer were also analyzed. Finally, we studied the effect of miR-20a and miR-203 on cell proliferation in cervical cancer cell lines by MTT. We found that the expression level of miR-20a (P<0.001) was significantly higher in cervical cancer patients than in healthy controls, while that of miR-203 (P<0.001) was lower. Aberrant expression of miR-20a was correlated with lymph node metastasis (LNM), histological grade and tumor diameter, but down-regulated miR-203 was correlated with LNM only. Furthermore, we found that over-expression of miR-203 decreased cell proliferation, while reduction of miR-20a also prevented tumor progression. Our results support the involvement of miR-20a and miR-203 in cervical tumorigenesis. We propose that miRNAs might be used as therapeutic agents for cervical cancer.


연구 과제 주관 기관 : Natural Science Foundation of Guangxi


  1. Baffa R, Fassan M, Volinia S, et al (2009). MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol, 219, 214-21.
  2. Boldrup L, Coates PJ, Wahlgren M, et al (2012). Subsite-based alterations in miR-21, miR-125b, and miR-203 in squamous cell carcinoma of the oral cavity and correlation to important target proteins. J Carcinog, 11, 18.
  3. Botezatu A, Goia-Rusanu CD, Iancu IV, et al (2011). Quantitative analysis of the relationship between microRNA 124a,-34b and-203 gene methylation and cervical oncogenesis. Mol Med Report, 4, 121-8.
  4. Cheung TH, Man KN, Yu MY, et al (2012). Dysregulated microRNAs in the pathogenesis and progression of cervical neoplasm. Cell Cycle, 11, 2876-84.
  5. Craig VJ, Cogliatti SB, Rehrauer H, et al (2011). Epigenetic silencing of microRNA-203 dysregulates ABL1 expression and drives Helicobacter-associated gastric lymphomagenesis. Cancer Res, 71, 3616-24.
  6. Flynt AS , Lai EC (2008). Biological principles of microRNAmediated regulation: shared themes amid diversity. Nat Rev Genet, 9, 831-42.
  7. Gu J, Wang Y, Wu X (2013). MicroRNA in the Pathogenesis and Prognosis of Esophageal Cancer. Curr Pharm Des, 19, 1292-300.
  8. Hayashita Y, Osada H, Tatematsu Y, et al (2005). A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res, 65, 9628-32.
  9. Huang G, Nishimoto K, Zhou Z, et al (2012). miR-20a encoded by the miR-17-92 cluster increases the metastatic potential of osteosarcoma cells by regulating Fas expression. Cancer Res, 72, 908-16.
  10. Hu X, Schwarz JK, Lewis JS Jr, et al (2010). A microRNA expression signature for cervical cancer prognosis. Cancer Res, 70, 1441-8.
  11. Jiang J, Lee EJ, Gusev Y, et al (2005). Real-time expression profiling of microRNA precursors in human cancer cell lines. Nucl Acids Res, 33, 5394-403.
  12. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.
  13. Kang HW, Wang F, Wei Q, et al (2012). miR-20a promotes migration and invasion by regulating TNKS2 in human cervical cancer cells. FEBS Lett, 586, 897-904.
  14. Lagos-Quintana M, Rauhut R, Lendeckel W, et al (2001). Identification of novel genes coding for small expressed RNAs. Science, 294, 853-8.
  15. Lee JW, Choi CH, Choi JJ, et al (2008). Altered microRNA expression in cervical carcinomas. Clin Cancer Res, 14, 2535-42.
  16. Lee RC, Ambros V (2001). An extensive class of small RNAs in Caenorhabditis elegans. Science, 294, 862-4.
  17. Lee YM, Chen HW, Maurya PK, et al (2012). MicroRNA regulation via DNA methylation during the morula to blastocyst transition in mice. Mol Hum Reprod, 18, 184-93.
  18. Lewis BP, Burge CB , Bartel DP (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 14, 15-20.
  19. Lin PC, Chiu YL, Banerjee S, et al (2013). Epigenetic repression of miR-31 disrupts androgen receptor homeostasis and contributes to prostate cancer progression. Cancer Res, 73, 1232-44.
  20. Luan S, Sun L, Huang F (2010). MicroRNA-34a: a novel tumor suppressor in p53-mutant glioma cell line U251. Arch Med Res, 41, 67-74.
  21. Lu J, Getz G, Miska EA, et al (2005). MicroRNA expression profiles classify human cancers. Nature, 435, 834-8.
  22. Lu Y, Thomson JM, Wong HY, et al (2007). Transgenic overexpression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells. Dev Biol, 310, 442-53.
  23. Liang YJ, Wang QY, Zhou CX, et al (2013). MiR-124 Targets Slug to Regulate Epithelial-to-Mesenchymal Transition and Metastasis of Breast Cancer. Carcinogenesis, 34, 713-22.
  24. Li JY, Zhang Y, Zhang WH, et al (2012). Differential distribution of miR-20a and miR-20b may underly metastatic heterogeneity of breast cancers. Asian Pac J Cancer Prev, 13, 1901-6.
  25. Lodish HF, Zhou B, Liu G, et al (2008). Micromanagement of the immune system by microRNAs. Nat Rev Immuno, l8, 120-30.
  26. Madhavan D, Zucknick M, Wallwiener M, et al (2012). Circulating miRNAs as surrogate markers for circulating tumor cells and prognostic markers in metastatic breast cancer. Clin Cancer Res, 18, 5972-82.
  27. Ma Y, Zhang P, Wang F, et al (2012). Elevated oncofoetal miR-17-5p expression regulates colorectal cancer progression by repressing its target gene P130. Nat Commun, 3, 1291.
  28. Naoki I, Kenoki O, Kazuhiro M, et al (2010). MicroRNA-203 expression as a new prognostic marker of pancreatic adenocarcinoma. Ann Surg Oncol, 17, 3120-28.
  29. Ota A, Tagawa H, Karnan S, et al (2004). Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res, 64, 3087-95.
  30. Stadler BM, Ruohola-Baker H (2008). Small RNAs: keeping stem cells in line. Cell, 132, 563-6.
  31. Takeshita N, Mori M, Kano M, et al (2012). miR-203 inhibits the migration and invasion of esophageal squamous cell carcinoma by regulating LASP1. Int J Oncol, 41, 1653-61.
  32. Ventura A, Young AG, Winslow MM, et al (2008). Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell, 132, 875-86.
  33. Venturini L, Battmer K, Castoldi M, et al (2007). Expression of the miR-17-92 polycistron in chronic myeloid leukemia (CML) CD34+ cells. Blood, 109, 4399-405.
  34. Viticchie G, Lena AM, Latina A, et al (2011). MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines. Cell Cycle, 10, 1121-31.
  35. Wang W, Corrigan-Cummins M, Hudson J, et al (2012). MicroRNA profiling of follicular lymphoma identifies microRNAs related to cell proliferation and tumor response. Haematologica, 97, 586-94.
  36. Xiao C, Srinivasan L, Calado DP, et al (2008). Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol, 9, 405-14.
  37. Yuan Y, Zeng ZY, Liu XH, et al (2011). MicroRNA-203 inhibits cell proliferation by repressing $\Delta$Np63 expression in human esophageal squamous cell carcinoma. BMC Cancer, 11, 57.

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  1. Upregulation of microRNA-203 is associated with advanced tumor progression and poor prognosis in epithelial ovarian cancer vol.30, pp.3, 2013,
  2. Inheritable changes in miRNAs expression in HeLa cells after X-ray and mitomycin C treatment vol.50, pp.8, 2014,
  3. Epigenetic Regulation of microRNAs in Gastric Cancer vol.59, pp.4, 2014,
  4. miR-203 Acts as a Tumor Suppressor Gene in Osteosarcoma by Regulating RAB22A vol.10, pp.9, 2015,
  5. Role of microRNAs in cancers of the female reproductive tract: insights from recent clinical and experimental discovery studies vol.128, pp.3, 2015,
  6. 'Drawing' a Molecular Portrait of CIN and Cervical Cancer: a Review of Genome-Wide Molecular Profiling Data vol.16, pp.11, 2015,
  7. Impact of Nutrition on Non-Coding RNA Epigenetics in Breast and Gynecological Cancer vol.2, pp.2296-861X, 2015,
  8. miR-31 functions as an oncogene in cervical cancer vol.292, pp.5, 2015,
  9. Integrated analysis of the miRNA, gene and pathway regulatory network in gastric cancer vol.35, pp.2, 2015,
  10. Mining featured micro ribonucleic acids associated with lung cancer based on bioinformatics vol.6, pp.4, 2015,
  11. MicroRNA and gynecologic cancers vol.42, pp.6, 2016,
  12. Evaluation of Plasma MicroRNAs as Diagnostic and Prognostic Biomarkers in Pancreatic Adenocarcinoma: miR-196a and miR-210 Could Be Negative and Positive Prognostic Markers, Respectively vol.2017, pp.2314-6141, 2017,
  13. Effect of EBI3 on radiation-induced immunosuppression of cervical cancer HeLa cells by regulating Treg cells through PD-1/PD-L1 pathway vol.39, pp.3, 2017,
  14. Multistep Model of Cervical Cancer: Participation of miRNAs and Coding Genes vol.15, pp.9, 2014,
  15. vol.23, pp.6, 2014,
  16. Microarray analysis revealed markedly differential miRNA expression profiles in cervical intraepithelial neoplasias and invasive squamous cell carcinoma vol.10, pp.13, 2014,
  17. A systematic study on dysregulated microRNAs in cervical cancer development vol.138, pp.6, 2015,
  18. Investigation of differentially-expressed microRNAs and genes in cervical cancer using an integrated bioinformatics analysis vol.13, pp.4, 2017,
  19. Cervical Cancer Markers: Epigenetics and microRNAs vol.49, pp.2, 2018,
  20. MiR-20a, a novel promising biomarker to predict prognosis in human cancer: a meta-analysis vol.18, pp.1, 2018,
  21. -CATENIN signal pathway vol.70, pp.3, 2018,
  22. Aberrant Expression of Some Circulating miRNAs in Childhood Acute Lymphoblastic Leukemia vol.56, pp.4, 2018,
  23. Expression of microRNAs 16, 20a, 150 and 155 in anal squamous intraepithelial lesions from high-risk groups vol.9, pp.1, 2019,