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Meta-analysis of microRNA expression profiling studies in human cervical cancer

Medical Oncology volume 32, Article number: 169 (2015) Cite this article

Abstract

Cervical cancer is one of the most common malignant tumors in women, and numerous studies have associated the disease with changes in microRNA (miRNA) expression. This meta-analysis aimed to consolidate and assess the results of these studies in order to identify potential miRNA biomarkers of cervical cancer. We systematically searched the literature for studies comparing miRNA expression between cervical cancer tissues and normal cervical tissues, and we meta-analyzed the result of 27 studies comprising 1,132 cancer samples and 943 normal samples. We used a vote-counting strategy that took into account total sample and mean fold-change, in order to comprehensively assess associations between certain miRNAs and cervical cancer occurrence and progression. The studies described 195 miRNAs that were significantly up-regulated and 96 microRNAs that were down-regulated in cervical cancer tissues (stage I–IV) relative to normal cervical tissues. Vote-counting analysis showed that up-regulation was most consistently reported for miR-20a and miR-21 (four studies), followed by miR-10a, miR-15b, miR-20b, miR-141, miR-200a, and miR-224 (three studies). Down-regulation was reported most consistently for miR-143 (seven studies), followed by miR-203 and miR-145 (six studies). Fourteen miRNA, respectively, showed a significantly correlated lymphatic node metastasis in eight studies. This meta-analysis has identified several miRNAs whose expression correlates reliably with cervical cancer. These should be probed in further studies to explore their potential as diagnostic biomarkers.

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References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.

    Article  PubMed  Google Scholar 

  2. Zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer. 2002;2(5):342–50.

    Article  CAS  PubMed  Google Scholar 

  3. Cummins JM, Velculescu VE. Implications of micro-RNA profiling for cancer diagnosis. Oncogene. 2006;25(46):6220–7.

    Article  CAS  PubMed  Google Scholar 

  4. Michael MZ, O’Connor SM, van Holst Pellekaan NG, Young GP, James RJ. Reduced accumulation of specific microRNAs in colorectal neoplasia. MCR. 2003;1(12):882–91.

    CAS  PubMed  Google Scholar 

  5. Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM. Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 2003;113(1):25–36.

    Article  CAS  PubMed  Google Scholar 

  6. Johnston RJ, Hobert O. A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature. 2003;426(6968):845–9.

    Article  CAS  PubMed  Google Scholar 

  7. Guan P, Yin Z, Li X, Wu W, Zhou B. Meta-analysis of human lung cancer microRNA expression profiling studies comparing cancer tissues with normal tissues. J Exp Clin Cancer Res. 2012;31:54.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Griffith OL, Melck A, Jones SJ, Wiseman SM. Meta-analysis and meta-review of thyroid cancer gene expression profiling studies identifies important diagnostic biomarkers. J Clin Oncol. 2006;24(31):5043–51.

    Article  CAS  PubMed  Google Scholar 

  9. Boeri M, Verri C, Conte D, et al. MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer. Proc Natl Acad Sci USA. 2011;108(9):3713–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Chan SK, Griffith OL, Tai IT, Jones SJ. Meta-analysis of colorectal cancer gene expression profiling studies identifies consistently reported candidate biomarkers. Cancer Epidemiol Biomark Prev. 2008;17(3):543–52.

    Article  CAS  Google Scholar 

  11. Lin C, Huang F, Zhang YJ, Tuokan T, Kuerban G. Roles of MiR-101 and its target gene Cox-2 in early diagnosis of cervical cancer in Uygur women. APJCP. 2014;15(1):45–8.

    PubMed  Google Scholar 

  12. Li XR, Chu HJ, Lv T, Wang L, Kong SF, Dai SZ. miR-342-3p suppresses proliferation, migration and invasion by targeting FOXM1 in human cervical cancer. FEBS Lett. 2014;588(17):3298–307.

  13. Chen Y, Ma C, Zhang W, Chen Z, Ma L. Down regulation of miR-143 is related with tumor size, lymph node metastasis and HPV16 infection in cervical squamous cancer. Diagn Pathol. 2014;9:88.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Zhao S, Yao DS, Chen JY, Ding N. Aberrant expression of miR-20a and miR-203 in cervical cancer. APJCP. 2013;14(4):2289–93.

    PubMed  Google Scholar 

  15. Zhang J, Zheng F, Yu G, Yin Y, Lu Q. miR-196a targets netrin 4 and regulates cell proliferation and migration of cervical cancer cells. Biochem Biophys Res Commun. 2013;440(4):582–8.

    Article  CAS  PubMed  Google Scholar 

  16. Yu Y, Zhang Y, Zhang S. MicroRNA-92 regulates cervical tumorigenesis and its expression is upregulated by human papillomavirus-16 E6 in cervical cancer cells. Oncol Lett. 2013;6(2):468–74.

    PubMed Central  PubMed  Google Scholar 

  17. Yu Q, Liu SL, Wang H, Shi G, Yang P, Chen XL. miR-126 suppresses the proliferation of cervical cancer cells and alters cell sensitivity to the chemotherapeutic drug bleomycin. APJCP. 2013;14(11):6569–72.

    Google Scholar 

  18. Yamamoto N, Kinoshita T, Nohata N, et al. Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion by targeting focal adhesion pathways in cervical squamous cell carcinoma. Int J Oncol. 2013;42(5):1523–32.

    PubMed Central  CAS  PubMed  Google Scholar 

  19. Xu J, Li Y, Wang F, et al. Suppressed miR-424 expression via upregulation of target gene Chk1 contributes to the progression of cervical cancer. Oncogene. 2013;32(8):976–87.

    Article  CAS  PubMed  Google Scholar 

  20. Xing AY, Wang B, Shi DB, et al. Deregulated expression of miR-145 in manifold human cancer cells. Exp Mol Pathol. 2013;95(1):91–7.

    Article  CAS  PubMed  Google Scholar 

  21. Tang T, Wong HK, Gu W, et al. MicroRNA-182 plays an onco-miRNA role in cervical cancer. Gynecol Oncol. 2013;129(1):199–208.

    Article  CAS  PubMed  Google Scholar 

  22. Shen SN, Wang LF, Jia YF, Hao YQ, Zhang L, Wang H. Upregulation of microRNA-224 is associated with aggressive progression and poor prognosis in human cervical cancer. Diagn Pathol. 2013;8:69.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Luo M, Shen D, Zhou X, Chen X, Wang W. MicroRNA-497 is a potential prognostic marker in human cervical cancer and functions as a tumor suppressor by targeting the insulin-like growth factor 1 receptor. Surgery. 2013;153(6):836–47.

    Article  PubMed  Google Scholar 

  24. Chen J, Yao D, Li Y, et al. Serum microRNA expression levels can predict lymph node metastasis in patients with early-stage cervical squamous cell carcinoma. Int J Mol Med. 2013;32(3):557–67.

    PubMed Central  CAS  PubMed  Google Scholar 

  25. Xie H, Zhao Y, Caramuta S, Larsson C, Lui WO. miR-205 expression promotes cell proliferation and migration of human cervical cancer cells. PLoS ONE. 2012;7(10):e46990.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Rao Q, Shen Q, Zhou H, Peng Y, Li J, Lin Z. Aberrant microRNA expression in human cervical carcinomas. Med Oncol. 2012;29(2):1242–8.

    Article  CAS  PubMed  Google Scholar 

  27. Ma D, Zhang YY, Guo YL, Li ZJ, Geng L. Profiling of microRNA-mRNA reveals roles of microRNAs in cervical cancer. Chin Med J. 2012;125(23):4270–6.

    CAS  PubMed  Google Scholar 

  28. Liu L, Wang YL, Wang JF. Differential expression of miR-21, miR-126, miR-143, miR-373 in normal cervical tissue, cervical cancer tissue and Hela cell. Sichuan da xue xue bao Yi xue ban = J Sichuan Univ Med Sci ed. 2012;43(4):536–9.

  29. Cheung TH, Man KN, Yu MY, et al. Dysregulated microRNAs in the pathogenesis and progression of cervical neoplasm. Cell Cycle. 2012;11(15):2876–84.

    Article  CAS  PubMed  Google Scholar 

  30. Wang F, Li Y, Zhou J, et al. miR-375 is down-regulated in squamous cervical cancer and inhibits cell migration and invasion via targeting transcription factor SP1. Am J Pathol. 2011;179(5):2580–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Tian RQ, Wang XH, Hou LJ, et al. MicroRNA-372 is down-regulated and targets cyclin-dependent kinase 2 (CDK2) and cyclin A1 in human cervical cancer, which may contribute to tumorigenesis. J Biol Chem. 2011;286(29):25556–63.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Muralidhar B, Winder D, Murray M, et al. Functional evidence that Drosha overexpression in cervical squamous cell carcinoma affects cell phenotype and microRNA profiles. J Pathol. 2011;224(4):496–507.

    Article  CAS  PubMed  Google Scholar 

  33. Li JH, Xiao X, Zhang YN, et al. MicroRNA miR-886-5p inhibits apoptosis by down-regulating Bax expression in human cervical carcinoma cells. Gynecol Oncol. 2011;120(1):145–51.

    Article  CAS  PubMed  Google Scholar 

  34. Deftereos G, Corrie SR, Feng Q, et al. Expression of mir-21 and mir-143 in cervical specimens ranging from histologically normal through to invasive cervical cancer. PLoS ONE. 2011;6(12):e28423.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Li B, Hu Y, Ye F, Li Y, Lv W, Xie X. Reduced miR-34a expression in normal cervical tissues and cervical lesions with high-risk human papillomavirus infection. Int J Gynecol Cancer. 2010;20(4):597–604.

    Article  PubMed  Google Scholar 

  36. Wang X, Tang S, Le SY, et al. Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS ONE. 2008;3(7):e2557.

    Article  PubMed Central  PubMed  Google Scholar 

  37. Lee JW, Choi CH, Choi JJ, et al. Altered MicroRNA expression in cervical carcinomas. Clin Cancer Res. 2008;14(9):2535–42.

    Article  CAS  PubMed  Google Scholar 

  38. Hayashita Y, Osada H, Tatematsu Y, et al. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res. 2005;65(21):9628–32.

    Article  CAS  PubMed  Google Scholar 

  39. Venturini L, Battmer K, Castoldi M, et al. Expression of the miR-17-92 polycistron in chronic myeloid leukemia (CML) CD34 + cells. Blood. 2007;109(10):4399–405.

    Article  CAS  PubMed  Google Scholar 

  40. Krichevsky AM, Gabriely G. miR-21: a small multi-faceted RNA. J Cell Mol Med. 2009;13(1):39–53.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Asangani IA, Rasheed SA, Nikolova DA, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 2008;27(15):2128–36.

    Article  CAS  PubMed  Google Scholar 

  42. Yao Q, Xu H, Zhang QQ, Zhou H, Qu LH. MicroRNA-21 promotes cell proliferation and down-regulates the expression of programmed cell death 4 (PDCD4) in HeLa cervical carcinoma cells. Biochem Biophys Res Commun. 2009;388(3):539–42.

    Article  CAS  PubMed  Google Scholar 

  43. Volinia S, Calin GA, Liu CG, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 2006;103(7):2257–61.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Akao Y, Nakagawa Y, Iio A, Naoe T. Role of microRNA-143 in Fas-mediated apoptosis in human T-cell leukemia Jurkat cells. Leuk Res. 2009;33(11):1530–8.

    Article  CAS  PubMed  Google Scholar 

  45. Kodahl AR, Lyng MB, Binder H, et al. Novel circulating microRNA signature as a potential non-invasive multi-marker test in ER-positive early-stage breast cancer: a case control study. Mol Oncol. 2014;8(5):874–83.

    Article  CAS  PubMed  Google Scholar 

  46. Cho WC, Chow AS, Au JS. Restoration of tumour suppressor hsa-miR-145 inhibits cancer cell growth in lung adenocarcinoma patients with epidermal growth factor receptor mutation. Eur J Cancer. 2009;45(12):2197–206.

    Article  CAS  PubMed  Google Scholar 

  47. Kou B, Gao Y, Du C, et al. miR-145 inhibits invasion of bladder cancer cells by targeting PAK1. Urol Oncol. 2014;32(6):846–54.

    Article  CAS  PubMed  Google Scholar 

  48. Hailer A, Grunewald TG, Orth M, et al. Loss of tumor suppressor mir-203 mediates overexpression of LIM and SH3 protein 1 (LASP1) in high-risk prostate cancer thereby increasing cell proliferation and migration. Oncotarget. 2014;5(12):2918–4153.

    Google Scholar 

  49. Kozaki K, Imoto I, Mogi S, Omura K, Inazawa J. Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. Cancer Res. 2008;68(7):2094–105.

    Article  CAS  PubMed  Google Scholar 

  50. Chang CC, Yang YJ, Li YJ, et al. MicroRNA-17/20a functions to inhibit cell migration and can be used a prognostic marker in oral squamous cell carcinoma. Oral Oncol. 2013;49(9):923–31.

    Article  CAS  PubMed  Google Scholar 

  51. Zhu W, Xu B. MicroRNA-21 identified as predictor of cancer outcome: a meta-analysis. PLoS ONE. 2014;9(8):e103373.

    Article  PubMed Central  PubMed  Google Scholar 

  52. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120(1):15–20.

    Article  CAS  PubMed  Google Scholar 

  53. Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834–8.

    Article  CAS  PubMed  Google Scholar 

  54. Babak T, Zhang W, Morris Q, Blencowe BJ, Hughes TR. Probing microRNAs with microarrays: tissue specificity and functional inference. RNA. 2004;10(11):1813–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Chandran UR, Dhir R, Ma C, Michalopoulos G, Becich M, Gilbertson J. Differences in gene expression in prostate cancer, normal appearing prostate tissue adjacent to cancer and prostate tissue from cancer free organ donors. BMC Cancer. 2005;5:45.

    Article  PubMed Central  PubMed  Google Scholar 

  56. Woenckhaus M, Grepmeier U, Wild PJ, et al. Multitarget FISH and LOH analyses at chromosome 3p in non-small cell lung cancer and adjacent bronchial epithelium. Am J Clin Pathol. 2005;123(5):752–61.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81060219).

Conflict of interest

The authors disclose no conflicts.

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  1. Department of Gynecology, People’s Hospital of Guangxi Zhuang Autonomous Region, Tao Yuan Rd. 6, Nanning, 530021, People’s Republic of China

    Mei-Yi Li & Xiao-Xia Hu

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  1. Mei-Yi Li
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  2. Xiao-Xia Hu
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Correspondence to Xiao-Xia Hu.

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Li, MY., Hu, XX. Meta-analysis of microRNA expression profiling studies in human cervical cancer. Med Oncol 32, 169 (2015). https://doi.org/10.1007/s12032-015-0510-5

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  • DOI: https://doi.org/10.1007/s12032-015-0510-5

Keywords

  • microRNAs
  • Profiling
  • Cervical cancer
  • Meta-analysis