Downregulated MiR-181a Alleviates HO-induced Oxidative Stress and Cellular Senescence by Targeting PDIA6 in Human Foreskin Fibroblasts

Overview

Journal An Bras Dermatol

Specialty Dermatology

Date 2022 Oct 16

PMID 36244946

Authors

Yan Huang

Huimin Yan

Yanqing Yang

Jinfei Zhou

Qijun Xu

Hu Meng

Affiliations

Soon will be listed here.

Abstract

Background: Oxidative stress is strongly associated with cellular senescence. Numerous studies have indicated that microRNAs (miRNAs) play a critical part in cellular senescence. MiR-181a was reported to induce cellular senescence, however, the potential mechanism of miR-181a in hydrogen peroxide (HO)-induced cellular senescence remains obscure.

Objective: The aim of this study is to investigate the role and regulatory mechanism of miR-181a in HO-induced cellular senescence.

Methods: Human foreskin fibroblasts (HFF) transfected with miR-181a inhibitor/miR-NC with or without HO treatment were divided into four groups: control + miR-NC/miR-181a inhibitor, HO + miR-NC/miR-181a inhibitor. CCK-8 assay was utilized to evaluate the viability of HFF. RT-qPCR was used to measure the expression of miR-181a and its target genes. Protein levels of protein disulfide isomerase family A member 6 (PDIA6) and senescence markers were assessed by western blotting. Senescence-associated β-galactosidase (SA-β-gal) staining was applied for detecting SA-β-gal activity. The activities of SOD, GPx, and CAT were detected by corresponding assay kits. The binding relation between PDIA6 and miR-181a was identified by luciferase reporter assay.

Results: MiR-181a inhibition suppressed HO-induced oxidative stress and cellular senescence in HFF. PDIA6 was targeted by miR-181a and lowly expressed in HO-treated HFF. Knocking down PDIA6 reversed miR-181a inhibition-mediated suppressive impact on HO-induced oxidative stress and cellular senescence in HFF.

Study Limitations: Signaling pathways that might be mediated by miR-181a/PDIA6 axis were not investigated.

Conclusion: Downregulated miR-181a attenuates HO-induced oxidative stress and cellular senescence in HFF by targeting PDIA6.

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