miR-144-3p inhibited the growth, metastasis and epithelial-mesenchymal transition of colorectal adenocarcinoma by targeting ZEB1/2

Aging (Albany NY). 2021 Jul 5;13(13):17349-17369. doi: 10.18632/aging.203225. Epub 2021 Jul 5.

Abstract

miR-144-3p is aberrantly expressed in several types of human cancer and functions as a tumor suppressor by inhibiting metastasis. However, the clinical significance and biological function of miR-144-3p in colorectal adenocarcinoma (CRA) have yet to be elucidated. Here we reported that miR-144-3p expression level was significantly down-regulated in CRA tissues compared with matched noncancerous colorectal mucosae tissues. Low miR-144-3p expression was correlated with adverse clinicopathologic characteristics and poor prognosis of CRA patients. Cox regression analysis showed that low miR-144-3p expression was an independent risk factor for DFS and OS in CRA. In vitro and in vivo assays showed that miR-144-3p significantly inhibited proliferation, migration and invasion of CRA cells. In particular, miR-144-3p could suppress EMT process of CRA cells by regulating the cytoskeleton and EMT markers. Bioinformatics analysis indicated that EMT associated transcription factors ZEB1 and ZEB2 were potential targets of miR-144-3p, and miR-144-3p inhibited ZEB1 and ZEB2 expression and was negatively correlated with their expression in CRA. Finally, we confirmed that ZEB1 and ZEB2 down-regulation collaboratively mediated the inhibitory effect of miR-144-3p on proliferation, invasion and EMT of CRA cells. In conclusion, our study provided evidence that miR-144-3p could inhibit CRA cell proliferation, invasion and EMT by targeting ZEB1/2.

Keywords: ZEB1/2; colorectal cancer; epithelial-mesenchymal transition; metastasis; miR-144-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Intestinal Mucosa / chemistry
  • Male
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Zinc Finger E-box Binding Homeobox 2 / genetics*
  • Zinc Finger E-box-Binding Homeobox 1 / genetics*

Substances

  • MIRN144 microRNA, human
  • MicroRNAs
  • ZEB1 protein, human
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2
  • Zinc Finger E-box-Binding Homeobox 1