Research Paper Volume 13, Issue 13 pp 17349—17369
miR-144-3p inhibited the growth, metastasis and epithelial-mesenchymal transition of colorectal adenocarcinoma by targeting ZEB1/2
- 1 Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China
- 2 Gastrointestinal Surgical Institute, Nanchang University, Nanchang 330006, Jiangxi, China
- 3 Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China
- 4 Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China
- 5 Department of General Surgery, Jiangxi Pingxiang People’s Hospital, Pingxiang 337000, Jiangxi, China
Received: November 23, 2020 Accepted: June 4, 2021 Published: July 5, 2021
https://doi.org/10.18632/aging.203225How to Cite
Copyright: © 2021 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Abbreviations
CRC: colorectal cancer; CRA: colorectal adenocarcinoma; qRT-PCR: quantitative real-time polymerase chain reaction; CRAT: colorectal adenocarcinoma tissues; NCMT: noncancerous colorectal mucosae tissues; DFS: disease free survival; OS: and overall survival; EMT: epithelial-mesenchymal transition; IHC: Immunohistochemistry; IF: Immunofluorescence; ZEB1/2: zinc finger E-box binding homeobox 1/2.