MYPT1 is targeted by miR-145 inhibiting viability, migration and invasion in 2D and 3D HeLa cultures

Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):348-354. doi: 10.1016/j.bbrc.2018.11.039. Epub 2018 Nov 14.

Abstract

The miR-143/145 cluster is down-regulated in cervical tumor cells suggesting a role in tumorigenesis including cytoskeleton remodeling, a key event for tumor progression. The aim of the present work was to determine the role of miR-143/145 in the modulation of the myosin regulator phospho-myosin light chain (pMLC). HeLa monolayer and tridimensional cultures were transfected with miR-143 or miR-145 mimics inhibiting cell viability, proliferation, migration and invasion, mainly through miR-145. MiR-145 transfection increased pMLC levels by targeting the MYPT1 subunit of the regulatory myosin phosphatase. MYPT1 knockdown by siRNAs reproduced miR-145 effects suggesting miR-145 as a tumor suppressor through MYPT1 targeting, leading to a subsequent increase of pMLC levels with implications for cervical cell viability, migration and invasion.

Keywords: Cervical cancer; MYPT1; Myosin phosphatase; miR-145; miRNA.

MeSH terms

  • Base Sequence
  • Cell Culture Techniques*
  • Cell Movement* / genetics
  • Cell Survival / genetics
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Keratinocytes / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Myosin Light Chains / metabolism
  • Myosin-Light-Chain Phosphatase / metabolism*
  • Neoplasm Invasiveness
  • Phosphorylation
  • RNA, Small Interfering / metabolism
  • Spheroids, Cellular / metabolism
  • Tumor Stem Cell Assay

Substances

  • MIRN145 microRNA, human
  • MicroRNAs
  • Myosin Light Chains
  • RNA, Small Interfering
  • Myosin-Light-Chain Phosphatase
  • PPP1R12A protein, human