MiR-199b-5p promotes tumor growth and metastasis in cervical cancer by down-regulating KLK10

Biochem Biophys Res Commun. 2018 Sep 5;503(2):556-563. doi: 10.1016/j.bbrc.2018.05.165. Epub 2018 Aug 2.

Abstract

MiR-199 b-5p and kallikrein-related peptidase 10 (KLK10) are related to various disease processes and pathogenesis. However, little is known about the molecular mechanisms of miR-199 b-5p and KLK10 in human cervical cancer. In the present study, we found that miR-199 b-5p was highly expressed in cervical cancer tissues and cell lines, and was positively correlated with overall survival (OS) and progression-free survival (PFS), higher incidences of larger tumor sizes, late International Federation of Gynecology and Obstetrics (FIGO) stages and preoperative metastasis. Further, we found that transfecting miR-199 b-5p mimics into cervical cancer cells promoted tumor progression through enhancing the cell viability, migration, and suppressing apoptosis by using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), wound healing and flow cytometry analysis. Luciferase reporter assays indicated that miR-199 b-5p targeted the 3'-untranslated region (3'-UTR) of KLK10. Over-expressing KLK10 reversed the role of miR-199 b-5p in accelerating cervical cancer progression. Suppressing miR-199 b-5p expressions improved apoptosis and reduced the cell viability, while the process was reversed in KLK10-knockdown cervical cancer cells. In vivo analysis verified the effects of miR-199 b-5p on promoting cervical cancer progression, accompanied with reduced KLK10 expressions. In summary, we identified that miR-199 b-5p played as a tumor promoter in cervical cancer cell growth by targeting KLK10, and miR-199 b-5p might function as a novel biomarker for diagnosis or therapeutic targets of human cervical cancer.

Keywords: Cervical cancer; KLK10; Migration; Proliferation; miR-199b-5p.

MeSH terms

  • 3' Untranslated Regions
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kallikreins / genetics*
  • MicroRNAs / genetics*
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • 3' Untranslated Regions
  • MicroRNAs
  • mirn199 microRNA, human
  • KLK10 protein, human
  • Kallikreins