Characterization of the MicroRNA Expression Profile of Cervical Squamous Cell Carcinoma Metastases

  • Ding, Hui (Department of Gynecology, Second Xiangya Hospital, Central-South University) ;
  • Wu, Yi-Lin (Department of Gynecology, Second Xiangya Hospital, Central-South University) ;
  • Wang, Ying-Xia (Department of Woman Health Care, Maternal and Child Health Hospital of Hunan Province) ;
  • Zhu, Fu-Fan (Department of Gynecology, Second Xiangya Hospital, Central-South University)
  • Published : 2014.02.28


Objectives: MicroRNAs (miRNAs) are important regulators of many physiological and pathological processes, including tumorigenesis and metastasis. In this study, we sought to determine the underlying molecular mechanisms of metastatic cervical carcinoma by performing miRNA profiling. Methods: Tissue samples were collected from ten cervical squamous cancer patients who underwent hysterectomy and pelvic lymph node (PLN) dissection in our hospital, including four PLN-positive (metastatic) cases and six PLN-negative (non-metastatic) cases. A miRNA microarray platform with 1223 probes was used to determine the miRNA expression profiles of these two tissue types and case groups. MiRNAs having at least 4-fold differential expression between PLN-positive and PLN-negative cervical cancer tissues were bioinformatically analyzed for target gene prediction. MiRNAs with tumor-associated target genes were validated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Results: Thirty-nine miRNAs were differentially expressed (>4-fold) between the PLN-positive and PLN-negative groups, of which, 22 were up-regulated and 17 were down-regulated. Sixty-nine percent of the miRNAs (27/39) had tumor-associated target genes, and the expression levels of six of those (miR-126, miR-96, miR-144, miR-657, miR-490-5p, and miR-323-3p) were confirmed by quantitative (q)RT-PCR. Conclusions: Six MiRNAs with predicted tumor-associated target genes encoding proteins that are known to be involved in cell adhesion, cytoskeletal remodeling, cell proliferation, cell migration, and apoptosis were identified. These findings suggest that a panel of miRNAs may regulate multiple and various steps of the metastasis cascade by targeting metastasis-associated genes. Since these six miRNAs are predicted to target tumor-associated genes, it is likely that they contribute to the metastatic potential of cervical cancer and may aid in prognosis or molecular therapy.


  1. Yu Q, Liu SL, Wang H, et al (2013). MiR-126 suppresses the proliferation of cervical cancer cells and alters cell sensitivity to the chemotherapeutic drug bleomycin. Asian Pac J Cancer Prev, 14, 6569-72
  2. Tavazoie SF, Alarco'n C, Oskarsson T, et al (2008). Endogenous human microRNAs that suppress breast cancer metastasis. Nature, 451, 147-52.
  3. Tsai WC, Hsu PW, Lai TC et al (2009). MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology, 49, 1571-82.
  4. Valastyan S, Reinhardt F, Benaich N, et al (2009). A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell, 137, 1032-46.
  5. Li N, Tang A, Huang S, et al (2013). MiR-126 suppresses colon cancer cell proliferation and invasion via inhibiting RhoA/ ROCK signaling pathway. Mol Cell Biochem, 380, 107-19.
  6. Korpal M, Lee ES, Hu G, et al (2008). 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, 283, 14910-4.
  7. Lee RC, Feinbaum RL, Ambros V (1993). The C. elegans heterochomic gene lin-4 encodes small RNAs with antisense complematarily to lin-4. Cell, 75, 843-54.
  8. Lewis BP, Burge CB, Bartel DP (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 120, 15-20.
  9. Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2-Delta Delta Ct method. Methods, 25, 402-8.
  10. Li SC, Tang P, Lin WC (2007). Intronic microRNA: discovery and biological implications. DNA Cell Biol, 26, 195-207.
  11. Li T, Li D, Sha J, et al (2009). MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells. Biochem Biophys Res Commun, 383, 280-5.
  12. Negrini M, Calin G A (2008). Breast cancer metastasis: a microRNA story. Breast Cancer Res, 10, 203.
  13. Pacurari M, Addison JB, Bondalapati N, et al (2013). The microRNA-200 family targets multiple non-small cell lung cancer prognostic markers in H1299 cells and BEAS-2B cells. Int J Oncol, 43, 548-60.
  14. Sohail F, Tavazoie, Alarcon C, Oskarsson T (2008). Endogenous human microRNAs that suppress breast cancer metastasis. Nature, 451, 147-52.
  15. Asangani IA, Rasheed SA, Nikolova DA, et al (2008). MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene, 27, 2128-36.
  16. Bagga S, Bracht J, Hunter S, et al (2005). Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell, 122, 553-63.
  17. Bartels CL, Tsongalis GJ (2009). MicroRNAs: novel biomarkers for human cancer. Clin Chem, 55, 623-31.
  18. Bartel DP (2004). MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell, 116, 281-97.
  19. Castoldi M, Schmidt S, Benes V, et al (2006). A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA). RNA, 12, 913-20.
  20. Esquela-Kerscher A, Slack FJ ( 2006). Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer, 6, 259-69.
  21. Feng R, Chen X, Yu Y , et al (2010). MiR-126 functions as a tumour suppressor in human gastric cancer. Cancer Lett, 298, 50-63.
  22. Garzon R, Calin GA, Croce CM (2009). MicroRNAs in Cancer. Annu Rev Med, 60, 167-79.
  23. Hashimoto Y, Akiyama Y, Yuasa Y (2013). Multiple-to-multiple relationships between microRNAs and target genes in gastric cancer. PLoS One, 8, e62589.
  24. He L, Hannon GJ (2004). MicroRNAs: Small RNAs with a big role in gene regulation. Nat Rev Genet, 5, 522-31.

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