Tumor Biology

, Volume 37, Issue 5, pp 6477–6483 | Cite as

MicroRNA-613 inhibited ovarian cancer cell proliferation and invasion by regulating KRAS

Original Article


MicroRNAs (miRNAs) play several important roles in carcinogenesis, and the dysregulation of miRNAs is associated with cancer progression. Little is known about the role of miR-613 in ovarian cancer. In the present study, we demonstrate that miR-613 expression is downregulated in human ovarian cancer cell lines and tissues. Additionally, miR-613 overexpression suppressed ovarian cancer cell proliferation, colony formation, and invasion. Furthermore, KRAS was identified as a target of miR-613. Reintroducing KRAS rescued the inhibitory effects exerted by miR-613 on ovarian cancer cell proliferation and invasion. Taken together, our findings suggest that miR-613 functions as a candidate tumor suppressor miRNA in ovarian cancer by directly targeting KRAS. To the best of our knowledge, this is the first study to show that miR-613 affects the proliferation and invasion of ovarian cancer.


Ovarian cancer MicroRNAs miR-613 KRAS 



This work was supported by the National Natural Science Foundation of China (Grant NO. 81301895) and Shandong Province Natural Science Foundation, China (Grant NO. ZR2012HQ009, NO. ZR2013HQ042)

Compliance with ethical standards

Ethics statement

All of the patients provided written informed consent. This study was approved by the Ethics Committee of Tianjin Medical University Cancer Institute and Hospital and complied with the Declaration of Helsinki.

Conflicts of interest


Supplementary material

13277_2015_4507_MOESM1_ESM.docx (13 kb)
Table S1 (DOCX 12 kb)


  1. 1.
    Maldonado L, Hoque MO. Epigenomics and ovarian carcinoma. Biomark Med. 2010;4:543–70.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Davidson B, Trope CG, Reich R. The clinical and diagnostic role of microRNAs in ovarian carcinoma. Gynecol Oncol. 2014;133:640–6.CrossRefPubMedGoogle Scholar
  3. 3.
    Montopoli M, Ragazzi E, Froldi G, Caparrotta L. Cell-cycle inhibition and apoptosis induced by curcumin and cisplatin or oxaliplatin in human ovarian carcinoma cells. Cell Prolif. 2009;42:195–206.CrossRefPubMedGoogle Scholar
  4. 4.
    Dong R, Liu X, Zhang Q, Jiang Z, Li Y, Wei Y, et al. miR-145 inhibits tumor growth and metastasis by targeting metadherin in high-grade serous ovarian carcinoma. Oncotarget. 2014;5:10816–29.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Tang Z, Ow GS, Thiery JP, Ivshina AV, Kuznetsov VA. Meta-analysis of transcriptome reveals let-7b as an unfavorable prognostic biomarker and predicts molecular and clinical subclasses in high-grade serous ovarian carcinoma. Int J Cancer. 2014;134:306–18.CrossRefPubMedGoogle Scholar
  6. 6.
    Hirata Y, Murai N, Yanaihara N, Saito M, Urashima M, Murakami Y, et al. MicroRNA-21 is a candidate driver gene for 17q23-25 amplification in ovarian clear cell carcinoma. BMC Cancer. 2014;14:799.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Tang H, Yao L, Tao X, Yu Y, Chen M, Zhang R, et al. miR-9 functions as a tumor suppressor in ovarian serous carcinoma by targeting tln1. Int J Mol Med. 2013;32:381–8.PubMedGoogle Scholar
  8. 8.
    Guo F, Cogdell D, Hu L, Yang D, Sood AK, Xue F, et al. miR-101 suppresses the epithelial-to-mesenchymal transition by targeting zeb1 and zeb2 in ovarian carcinoma. Oncol Rep. 2014;31:2021–8.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Liu Z, Liu J, Segura MF, Shao C, Lee P, Gong Y, et al. miR-182 overexpression in tumourigenesis of high-grade serous ovarian carcinoma. J Pathol. 2012;228:204–15.CrossRefPubMedGoogle Scholar
  10. 10.
    Yu X, Zhang X, Bi T, Ding Y, Zhao J, Wang C, et al. miRNA expression signature for potentially predicting the prognosis of ovarian serous carcinoma. Tumour Biol. 2013;34:3501–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Li Z, Lei H, Luo M, Wang Y, Dong L, Ma Y, et al. DNA methylation downregulated miR-10b acts as a tumor suppressor in gastric cancer. Gastric Cancer. 2015;18:43–54.CrossRefPubMedGoogle Scholar
  12. 12.
    Li Z, Yu X, Shen J, Jiang Y. MicroRNA dysregulation in uveal melanoma: a new player enters the game. Oncotarget. 2015.Google Scholar
  13. 13.
    Li Z, Yu X, Shen J, Chan MT, Wu WK. MicroRNA in intervertebral disc degeneration. Cell Prolif. 2015.Google Scholar
  14. 14.
    Bier A, Giladi N, Kronfeld N, Lee HK, Cazacu S, Finniss S, et al. MicroRNA-137 is downregulated in glioblastoma and inhibits the stemness of glioma stem cells by targeting rtvp-1. Oncotarget. 2013;4:665–76.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Li Z, Yu X, Shen J, Wu WK, Chan MT. MicroRNA expression and its clinical implications in Ewing’s sarcoma. Cell Prolif. 2015;48:1–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Yu X, Li Z. MicroRNAs regulate vascular smooth muscle cell functions in atherosclerosis (review). Int J Mol Med. 2014;34:923–33.PubMedGoogle Scholar
  17. 17.
    Yu X, Li Z, Shen J, Wu WK, Liang J, Weng X, et al. MicroRNA-10b promotes nucleus pulposus cell proliferation through rhoc-akt pathway by targeting hoxd10 in intervetebral disc degeneration. PLoS One. 2013;8, e83080.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Lee HK, Finniss S, Cazacu S, Bucris E, Ziv-Av A, Xiang C, et al. Mesenchymal stem cells deliver synthetic microRNA mimics to glioma cells and glioma stem cells and inhibit their cell migration and self-renewal. Oncotarget. 2013;4:346–61.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Li Z, Yu X, Wang Y, Shen J, Wu WK, Liang J, et al. By downregulating tiam1 expression, microRNA-329 suppresses gastric cancer invasion and growth. Oncotarget. 2014.Google Scholar
  20. 20.
    Furuta M, Kozaki K, Tanimoto K, Tanaka S, Arii S, Shimamura T, et al. The tumor-suppressive miR-497-195 cluster targets multiple cell-cycle regulators in hepatocellular carcinoma. PLoS One. 2013;8, e60155.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kulkarni S, Augoff K, Rivera L, McCue B, Khoury T, Groman A, et al. Increased expression levels of wave3 are associated with the progression and metastasis of triple negative breast cancer. PLoS One. 2012;7, e42895.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Saito A, Suzuki HI, Horie M, Ohshima M, Morishita Y, Abiko Y, et al. Correction: an integrated expression profiling reveals target genes of tgf-beta and tnf-alphah possibly mediated by microRNAs in lung cancer cells. PLoS One. 2014;9.Google Scholar
  23. 23.
    Ohdaira H, Sekiguchi M, Miyata K, Yoshida K. MicroRNA-494 suppresses cell proliferation and induces senescence in a549 lung cancer cells. Cell Prolif. 2012;45:32–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Fu LL, Zhao X, Xu HL, Wen X, Wang SY, Liu B, et al. Identification of microRNA-regulated autophagic pathways in plant lectin-induced cancer cell death. Cell Prolif. 2012;45:477–85.CrossRefPubMedGoogle Scholar
  25. 25.
    Luo X, Dong Z, Chen Y, Yang L, Lai D. Enrichment of ovarian cancer stem-like cells is associated with epithelial to mesenchymal transition through an miRNA-activated akt pathway. Cell Prolif. 2013;46:436–46.CrossRefPubMedGoogle Scholar
  26. 26.
    Huang J, Zhang SY, Gao YM, Liu YF, Liu YB, Zhao ZG, et al. MicroRNAs as oncogenes or tumour suppressors in oesophageal cancer: potential biomarkers and therapeutic targets. Cell Prolif. 2014;47:277–86.CrossRefPubMedGoogle Scholar
  27. 27.
    Li J, You T, Jing J. MiR-125b inhibits cell biological progression of Ewing’s sarcoma by suppressing the pi3k/akt signalling pathway. Cell Prolif. 2014;47:152–60.CrossRefPubMedGoogle Scholar
  28. 28.
    Zhong D, Zhang Y, Zeng YJ, Gao M, Wu GZ, Hu CJ, et al. MicroRNA-613 represses lipogenesis in hepg2 cells by downregulating lxralpha. Lipids Health Dis. 2013;12:32.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Zhao R, Feng J, He G. MiR-613 regulates cholesterol efflux by targeting lxralpha and abca1 in ppargamma-activated thp-1 macrophages. Biochem Biophys Res Commun. 2014;448:329–34.CrossRefPubMedGoogle Scholar
  30. 30.
    Yang Z, Yuan Z, Fan Y, Deng X, Zheng Q. Integrated analyses of microRNA and mRNA expression profiles in aggressive papillary thyroid carcinoma. Mol Med Rep. 2013;8:1353–8.PubMedGoogle Scholar
  31. 31.
    Ou Z, Wada T, Gramignoli R, Li S, Strom SC, Huang M, et al. MicroRNA hsa-miR-613 targets the human lxralpha gene and mediates a feedback loop of lxralpha autoregulation. Mol Endocrinol. 2011;25:584–96.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    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;3:44–57.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Zhang WH, Gui JH, Wang CZ, Chang Q, Xu SP, Cai CH, et al. The identification of miR-375 as a potential biomarker in distal gastric adenocarcinoma. Oncol Res. 2012;20:139–47.CrossRefPubMedGoogle Scholar
  34. 34.
    Wang K, Jia Z, Zou J, Zhang A, Wang G, Hao J, et al. Analysis of hsa-miR-30a-5p expression in human gliomas. Pathol Oncol Res. 2013;19:405–11.CrossRefPubMedGoogle Scholar
  35. 35.
    Liang J, Zhang Y, Jiang G, Liu Z, Xiang W, Chen X, et al. MiR-138 induces renal carcinoma cell senescence by targeting ezh2 and is downregulated in human clear cell renal cell carcinoma. Oncol Res. 2013;21:83–91.CrossRefPubMedGoogle Scholar
  36. 36.
    Fei B, Wu H. MiR-378 inhibits progression of human gastric cancer mgc-803 cells by targeting mapk1 in vitro. Oncol Res. 2013;20:557–64.CrossRefGoogle Scholar
  37. 37.
    Zannoni GF, Improta G, Chiarello G, Pettinato A, Petrillo M, Scollo P, et al. Mutational status of kras, nras, and braf in primary clear cell ovarian carcinoma. Virchows Arch. 2014;465:193–8.CrossRefPubMedGoogle Scholar
  38. 38.
    Nodin B, Zendehrokh N, Sundstrom M, Jirstrom K. Clinicopathological correlates and prognostic significance of kras mutation status in a pooled prospective cohort of epithelial ovarian cancer. Diagn Pathol. 2013;8:106.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Kim M, Chen X, Chin LJ, Paranjape T, Speed WC, Kidd KK, et al. Extensive sequence variation in the 3′ untranslated region of the kras gene in lung and ovarian cancer cases. Cell Cycle. 2014;13:1030–40.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Gynecology Cancer, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Prevention and TherapyTianjin Medical University Cancer Institute and HospitalTianjinChina
  2. 2.Department of Radiation OncologyShandong Cancer Hospital and InstituteJinanChina

Personalised recommendations