miR-346 Up-regulates Argonaute 2 (AGO2) Protein Expression to Augment the Activity of Other MicroRNAs (miRNAs) and Contributes to Cervical Cancer Cell Malignancy

J Biol Chem. 2015 Dec 18;290(51):30342-50. doi: 10.1074/jbc.M115.691857. Epub 2015 Oct 30.

Abstract

MicroRNAs (miRNAs) are a class of post-transcriptional regulators of gene expression, and AGO2 is essential for miRNA activity. In this study, we focused on the regulation of AGO2 by miR-346 and the consequences in cervical cancer cells. miR-346 enhanced the expression of AGO2, resulting in the increased activity of other miRNAs and contributing to the malignancy of HeLa cells. GRSF1 participated in the regulation of AGO2 by miR-346, and the middle sequence of miR-346 was vital for the synergy effect of miR-346 and GRSF1. We determined that miR-346 promoted the migration and invasion of HeLa cells. In summary, we are the first to report that AGO2 is regulated positively by miRNA and that GRSF1 participates in the miRNA pathway.

Keywords: AGO2; GRSF1; eukaryotic initiation factor 2 (eIF2); gene activation; gene expression; gene regulation; miR-346; microRNA (miRNA); microRNA mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Argonaute Proteins / biosynthesis*
  • Argonaute Proteins / genetics
  • Cell Movement*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Poly(A)-Binding Proteins / biosynthesis
  • Poly(A)-Binding Proteins / genetics
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • Up-Regulation
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • AGO2 protein, human
  • Argonaute Proteins
  • GRSF1 protein, human
  • MIRN346 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • Poly(A)-Binding Proteins
  • RNA, Neoplasm