MicroRNA-214 suppresses growth, migration and invasion through a novel target, high mobility group AT-hook 1, in human cervical and colorectal cancer cells

Br J Cancer. 2016 Sep 6;115(6):741-51. doi: 10.1038/bjc.2016.234. Epub 2016 Aug 18.

Abstract

Background: MicroRNA-214 (miR-214) has been shown to act as a tumour suppressor in human cervical and colorectal cancer cells. The aim of this study was to experimentally validate high mobility group AT-hook 1 as a novel target for miR-214-mediated suppression of growth and motility.

Methods: HMGA1 and miR-214 expression levels were estimated in cervical and colorectal clinical specimens using qPCR. HMGA1 3' untranslated region luciferase assays were performed to validate HMGA1 as a target of miR-214. Effect of altering the expression of miR-214 or HMGA1 on proliferation, migration and invasion of human cervical and colorectal cancer cells was investigated.

Results: miR-214 expression was poor while that of HMGA1 was high in cervical and colorectal cancer tissues. miR-214-re-expression or HMGA1 downregulation inhibited proliferation, migration and invasion of cancer cells while miR-214 inhibition had opposite effects. miR-214 was demonstrated to bind to the wild-type 3' untranslated region of HMGA1 but not with its mutant.

Conclusions: Low expression of miR-214 concurrent with elevated levels of HMGA1 may contribute to cervical and colorectal cancer progression. miR-214-mediated regulation of HMGA1 is a novel mechanism for its tumour-suppressive actions in human cervical and colorectal cancer cells and opens up avenues for novel therapeutic strategies for these two cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HMGA1a Protein / antagonists & inhibitors
  • HMGA1a Protein / biosynthesis
  • HMGA1a Protein / genetics
  • HMGA1a Protein / physiology*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • RNA Interference
  • RNA, Neoplasm / genetics*
  • RNA, Small Interfering / genetics
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • 3' Untranslated Regions
  • MIRN214 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • RNA, Small Interfering
  • HMGA1a Protein