DOI QR코드

DOI QR Code

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)
  • Published : 2013.04.30

Abstract

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.

Acknowledgement

Supported by : Natural Science Foundation of Guangxi

References

  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. https://doi.org/10.1002/path.2586
  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. https://doi.org/10.4103/1477-3163.104006
  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. https://doi.org/10.4161/cc.21278
  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. https://doi.org/10.1158/0008-5472.CAN-10-3907
  6. Flynt AS , Lai EC (2008). Biological principles of microRNAmediated regulation: shared themes amid diversity. Nat Rev Genet, 9, 831-42. https://doi.org/10.1038/nrg2455
  7. Gu J, Wang Y, Wu X (2013). MicroRNA in the Pathogenesis and Prognosis of Esophageal Cancer. Curr Pharm Des, 19, 1292-300. https://doi.org/10.2174/138161213804805775
  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. https://doi.org/10.1158/0008-5472.CAN-05-2352
  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. https://doi.org/10.1158/0008-5472.CAN-11-1460
  10. Hu X, Schwarz JK, Lewis JS Jr, et al (2010). A microRNA expression signature for cervical cancer prognosis. Cancer Res, 70, 1441-8. https://doi.org/10.1158/0008-5472.CAN-09-3289
  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. https://doi.org/10.1093/nar/gki863
  12. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  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. https://doi.org/10.1016/j.febslet.2012.02.020
  14. Lagos-Quintana M, Rauhut R, Lendeckel W, et al (2001). Identification of novel genes coding for small expressed RNAs. Science, 294, 853-8. https://doi.org/10.1126/science.1064921
  15. Lee JW, Choi CH, Choi JJ, et al (2008). Altered microRNA expression in cervical carcinomas. Clin Cancer Res, 14, 2535-42. https://doi.org/10.1158/1078-0432.CCR-07-1231
  16. Lee RC, Ambros V (2001). An extensive class of small RNAs in Caenorhabditis elegans. Science, 294, 862-4. https://doi.org/10.1126/science.1065329
  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. https://doi.org/10.1093/molehr/gar072
  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. https://doi.org/10.1158/0008-5472.CAN-12-2968
  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. https://doi.org/10.1016/j.arcmed.2010.02.007
  21. Lu J, Getz G, Miska EA, et al (2005). MicroRNA expression profiles classify human cancers. Nature, 435, 834-8. https://doi.org/10.1038/nature03702
  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. https://doi.org/10.1016/j.ydbio.2007.08.007
  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. https://doi.org/10.1093/carcin/bgs383
  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. https://doi.org/10.7314/APJCP.2012.13.5.1901
  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. https://doi.org/10.1158/1078-0432.CCR-12-1407
  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. https://doi.org/10.1038/ncomms2276
  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. https://doi.org/10.1245/s10434-010-1188-8
  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. https://doi.org/10.1158/0008-5472.CAN-03-3773
  30. Stadler BM, Ruohola-Baker H (2008). Small RNAs: keeping stem cells in line. Cell, 132, 563-6. https://doi.org/10.1016/j.cell.2008.02.005
  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. https://doi.org/10.1016/j.cell.2008.02.019
  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. https://doi.org/10.1182/blood-2006-09-045104
  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. https://doi.org/10.4161/cc.10.7.15180
  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. https://doi.org/10.3324/haematol.2011.048132
  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. https://doi.org/10.1038/ni1575
  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. https://doi.org/10.1186/1471-2407-11-57

Cited by

  1. Upregulation of microRNA-203 is associated with advanced tumor progression and poor prognosis in epithelial ovarian cancer vol.30, pp.3, 2013, https://doi.org/10.1007/s12032-013-0681-x
  2. Inheritable changes in miRNAs expression in HeLa cells after X-ray and mitomycin C treatment vol.50, pp.8, 2014, https://doi.org/10.1134/S1022795414080092
  3. Epigenetic Regulation of microRNAs in Gastric Cancer vol.59, pp.4, 2014, https://doi.org/10.1007/s10620-013-2939-8
  4. miR-203 Acts as a Tumor Suppressor Gene in Osteosarcoma by Regulating RAB22A vol.10, pp.9, 2015, https://doi.org/10.1371/journal.pone.0132225
  5. Role of microRNAs in cancers of the female reproductive tract: insights from recent clinical and experimental discovery studies vol.128, pp.3, 2015, https://doi.org/10.1042/CS20140087
  6. 'Drawing' a Molecular Portrait of CIN and Cervical Cancer: a Review of Genome-Wide Molecular Profiling Data vol.16, pp.11, 2015, https://doi.org/10.7314/APJCP.2015.16.11.4477
  7. Impact of Nutrition on Non-Coding RNA Epigenetics in Breast and Gynecological Cancer vol.2, pp.2296-861X, 2015, https://doi.org/10.3389/fnut.2015.00016
  8. miR-31 functions as an oncogene in cervical cancer vol.292, pp.5, 2015, https://doi.org/10.1007/s00404-015-3713-2
  9. Integrated analysis of the miRNA, gene and pathway regulatory network in gastric cancer vol.35, pp.2, 2015, https://doi.org/10.3892/or.2015.4451
  10. Mining featured micro ribonucleic acids associated with lung cancer based on bioinformatics vol.6, pp.4, 2015, https://doi.org/10.1111/1759-7714.12187
  11. MicroRNA and gynecologic cancers vol.42, pp.6, 2016, https://doi.org/10.1111/jog.12995
  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, https://doi.org/10.1155/2017/6495867
  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, https://doi.org/10.1177/1010428317692237
  14. Multistep Model of Cervical Cancer: Participation of miRNAs and Coding Genes vol.15, pp.9, 2014, https://doi.org/10.3390/ijms150915700
  15. vol.23, pp.6, 2014, https://doi.org/10.1089/scd.2013.0308
  16. Microarray analysis revealed markedly differential miRNA expression profiles in cervical intraepithelial neoplasias and invasive squamous cell carcinoma vol.10, pp.13, 2014, https://doi.org/10.2217/fon.14.38
  17. A systematic study on dysregulated microRNAs in cervical cancer development vol.138, pp.6, 2015, https://doi.org/10.1002/ijc.29618
  18. Investigation of differentially-expressed microRNAs and genes in cervical cancer using an integrated bioinformatics analysis vol.13, pp.4, 2017, https://doi.org/10.3892/ol.2017.5766
  19. Cervical Cancer Markers: Epigenetics and microRNAs vol.49, pp.2, 2018, https://doi.org/10.1093/labmed/lmx080
  20. MiR-20a, a novel promising biomarker to predict prognosis in human cancer: a meta-analysis vol.18, pp.1, 2018, https://doi.org/10.1186/s12885-018-4907-3
  21. -CATENIN signal pathway vol.70, pp.3, 2018, https://doi.org/10.1002/iub.1720
  22. Aberrant Expression of Some Circulating miRNAs in Childhood Acute Lymphoblastic Leukemia vol.56, pp.4, 2018, https://doi.org/10.1007/s10528-018-9844-y
  23. Expression of microRNAs 16, 20a, 150 and 155 in anal squamous intraepithelial lesions from high-risk groups vol.9, pp.1, 2019, https://doi.org/10.1038/s41598-018-38378-6