Mechanism of OTUD5 in non‐small cell lung cancer cell proliferation, invasion, and migration
Open Access
- 27 June 2022
- journal article
- research article
- Published by Association of Basic Medical Sciences of FBIH in Bosnian Journal of Basic Medical Sciences
- Vol. 22 (6), 901-911
- https://doi.org/10.17305/bjbms.2022.7206
Abstract
Ovarian tumor protease deubiquitinase 5 (OTUD5) has been discussed as a regulator of cancer development. Herein, the current study set out to explore the molecular mechanism of OTUD5 in non‐small cell lung cancer (NSCLC) cell proliferation, invasion, and migration. Firstly, the expression patterns of OTUD5, phosphatase and tensin homolog (PTEN), as well as microRNA (miR)-652-3p in cells were detected by qRT-PCR and Western blot. Cell viability, migration, and invasion were assessed with the help of cell-counting kit-8 and Transwell assays, in addition to the measurement of the ubiquitination and protein levels of PTEN. The binding relations between OTUD5 and PTEN, and miR-652-3p and OTUD5 were testified by co-immunoprecipitation or dual-luciferase assays. Cells were further treated with GSK2643943A (inhibitor of deubiquitinase) or miR-652-3p-inhibitor to explore the role of PTEN ubiquitination and miR-652-3p in NSCLC cells. OTUD5 and PTEN were both poorly-expressed, and miR-652-3p was highly-expressed in NSCLC cells. On the other hand, over-expression of OTUD5 suppressed NSCLC cell proliferation, invasion, and migration. OTUD5 deubiquitinated and stabilized PTEN, and miR-652-3p targeted and inhibited OTUD5 expression. Augmenting the ubiquitination levels of PTEN promoted NSCLC cell growth, whereas miR-652-3p inhibition promoted the tumor-suppressing effects of the OTUD5/ PTEN axis in NSCLC. Altogether, our findings highlighted that miR-652-3p restrained the role of OTUD5 in deubiquitinating PTEN to improve PTEN protein level, thereby promoting NSCLC cell proliferation, invasion, and migration.Keywords
This publication has 57 references indexed in Scilit:
- Ubiquitination: Friend and foe in cancerThe International Journal of Biochemistry & Cell Biology, 2018
- PTEN/PTENP1: ‘Regulating the regulator of RTK-dependent PI3K/Akt signalling’, new targets for cancer therapyMolecular Cancer, 2018
- A MicroRNA/Ubiquitin Ligase Feedback Loop Regulates Slug-Mediated Invasion in Breast CancerNeoplasia, 2017
- GEPIA: a web server for cancer and normal gene expression profiling and interactive analysesNucleic Acids Research, 2017
- HypothesisAnti-Cancer Drugs, 2017
- Characterization of PTEN mutations in brain cancer reveals that pten mono-ubiquitination promotes protein stability and nuclear localizationOncogene, 2017
- MiR-652-3p is upregulated in non-small cell lung cancer and promotes proliferation and metastasis by directly targeting Lgl1Oncotarget, 2016
- starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq dataNucleic Acids Research, 2013
- OTUD5 Regulates p53 Stability by Deubiquitinating p53PLOS ONE, 2013
- PTEN in cancer, metabolism, and agingTrends in Endocrinology & Metabolism, 2012