Research Paper Volume 12, Issue 9 pp 7985—8000

PHLDA2 regulates EMT and autophagy in colorectal cancer via the PI3K/AKT signaling pathway

Zhan Ma 1, , Shuping Lou 2, , Zheng Jiang 1, ,

  • 1 Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
  • 2 Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

received: January 9, 2020 ; accepted: March 30, 2020 ; published: May 8, 2020 ;

https://doi.org/10.18632/aging.103117
How to Cite

Copyright © 2020 Ma 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

High levels of the imprinted gene pleckstrin homology like domain family A member 2 (PHLDA2) correlate with tumor progression in several malignancies. Here, we investigated the effects of PHDLDA2 expression in CRC through assays of cellular proliferation, invasion, migration, and apoptosis. We also screened for possible mechanisms of action. Our results show that PHLDA2 was upregulated in CRC tissues. Knockdown of PHLDA2 inhibited cellular proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) in vitro. Knockout of PHLDA2 promoted cellular apoptosis, in part by activating autophagy. PHLDA2 knockout also inhibited tumorigenesis and expression of KI67 protein in vivo. The effects of PHLDA2 on autophagy and EMT were mediated in part via the PI3K/AKT signaling pathway. Taken together, these results suggest that downregulation of PHLDA2 inhibits tumor growth and PI3K, thereby promoting autophagy and inhibiting EMT, in part through the PI3K/AKT/mTOR and PI3K/AKT/GSK-3β signaling pathways.

Abbreviations

CRC: colorectal cancer; RT-qPCR: reverse transcription-quantitative polymerase chain reaction; CCK8: Cell Counting Kit-8; EMT: epithelial-mesenchymal transition.