Research Paper Volume 12, Issue 13 pp 12812—12840
PHLPP2 is regulated by competing endogenous RNA network in pathogenesis of colon cancer
- 1 Department of Laboratory Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, P.R. China
- 2 Department of General Surgery, Changzheng Hospital, Naval Medical University, Shanghai 200003, P.R. China
Received: January 23, 2020 Accepted: April 18, 2020 Published: July 7, 2020
https://doi.org/10.18632/aging.103246How to Cite
Copyright © 2020 Wu 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
Recently, homologous pleckstrin-homology (PH)-domain leucine-rich-repeat protein phosphatases (PHLPP2) has been reported as a tumor suppressor in colon cancer. This study aimed to unravel the possible involvement of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) regulating PHLPP2 in colon cancer. Expressions of candidate lncRNAs and miRNAs were verified by the RT-qPCR and Western blot analyses in colon cancer. The roles of candidate genes in colon cancer were investigated in HT-29 cells in vitro and in mouse tumor xenograft model in vivo. PHLPP2, a target of miR-141 and miR-424, was downregulated in colon cancer. PHLPP2 upregulation and miR-141 and miR-424 downregulation suppressed the colon cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition, and promote cell apoptosis, which also resulted in suppression of tumor metastasis and formation. Furthermore, LINC00402, LINC00461, and SFTA1P were identified as the targets of miR-141 and miR-424 and acted as competitive endogenous RNAs (ceRNAs) of PHLPP2. The upregulation of LINC00402, LINC00461, and SFTA1P was verified to enhance the suppressive effects of PHLPP2 in the pathogenesis of colon cancer. Conjointly, our results demonstrated the suppressive effects of PHLPP2 in colon cancer and proved that LINC00402, LINC00461, and SFTA1P acted as ceRNAs of PHLPP2 by competitive binding to miR-141 and miR-424.
Abbreviations
DEGs: differentially expressed genes; EMT: epithelial-mesenchymal transition; ncRNAs: non-coding RNAs; miRNAs: microRNAs; lncRNAs: long noncoding RNAs; ceRNAs: competing endogenous RNAs; PH: pleckstrin-homology; SFTA1P: Surfactant associated 1, pseudogene; LINC00461: long intergenic non-protein coding RNA 461; LINC00402: long intergenic non-protein coding RNA 402; GEO: gene expression omnibus; KEGG: Kyoto encyclopedia of genes and genomes; OS: overall survival; ISH: in situ hybridization; FISH: fluorescence in situ hybridization; DMEM: Dulbecco's modified eagle medium; RT-qPCR: reverse transcription quantitative polymerase chain reaction; PMSF: phenylmethylsulfonyl fluoride; EdU: 5-ethynyl-2’-deoxyuridine; RIP: RNA immunoprecipitation; SPF: specific pathogen-free; SD: standard deviation.