MYPT1 inhibits the metastasis of renal clear cell carcinoma via the MAPK8/N-cadherin pathway

FEBS Open Bio. 2022 Nov;12(11):2083-2095. doi: 10.1002/2211-5463.13487. Epub 2022 Sep 27.

Abstract

Myosin phosphatase target subunit 1 (MYPT1) is a subunit of myosin phosphatase that is capable of regulating smooth muscle contraction. MYPT1 has been reported to be involved in a wide variety of tumours, but its expression and biological functions in renal clear cell carcinoma (ccRCC) remain obscure. Herein, we analysed the relationship between patient clinicopathological characteristics and MYPT1 expression levels in ccRCC patients using a tissue microarray (TMA) and data retrieved from the TCGA-KIRC dataset. MYPT1 was overexpressed or depleted using siRNA in ccRCC cells to assess the effects on migration and invasion in vitro and in vivo. Additionally, RNA-sequencing and bioinformatics analysis were performed to investigate the precise mechanism. MYPT1 expression in ccRCC tissues was observed to be lower than that in nonmalignant tissues (P < 0.05). In addition, MYPT1 downregulation was closely linked to advanced pathological stage (P < 0.05), and poor OS (overall survival; P < 0.05). Functionally, increased expression of MYPT1 suppressed ccRCC migration and invasion in vitro, and inhibited tumour metastasis in vivo. In addition, MYPT1 overexpression exerted its suppressive effects via the MAPK8/N-cadherin pathway in ccRCC.

Keywords: MAPK; MYPT1; cadherin; metastasis; renal clear cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / genetics
  • Carcinoma, Renal Cell* / metabolism
  • Cell Movement / genetics
  • Humans
  • Kidney Neoplasms* / metabolism
  • Mitogen-Activated Protein Kinase 8 / metabolism
  • Myosin-Light-Chain Phosphatase / genetics
  • Myosin-Light-Chain Phosphatase / metabolism

Substances

  • Cadherins
  • Myosin-Light-Chain Phosphatase
  • PPP1R12A protein, human
  • Mitogen-Activated Protein Kinase 8