LncRNA SNHG8 Upregulates MUC5B to Induce Idiopathic Pulmonary Fibrosis Progression by Targeting MiR-4701-5p

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Jan 1

PMID 38163156

Authors

Xiaoping Zhang

Runxia Shao

Affiliations

Soon will be listed here.

Abstract

Long noncoding RNAs (lncRNAs) play a critical role in idiopathic pulmonary fibrosis (IPF); however, the underlying molecular mechanisms are unclear. Our study demonstrated that lncRNA small nucleolar RNA host gene 8 (SNHG8) was increased in bleomycin (BLM)-induced A549 cells. LncRNA SNHG8 overexpression further elevated fibrosis-related factors monocyte chemotactic protein 1 (MCP1), CC motif chemokine ligand 18 (CCL18), and α-smooth muscle actin (α-SMA), as well as increased collagen type I alpha-1 chain (COL1A1) and collagen type III alpha-1 chain (COL3A1). Meanwhile, lncRNA SNHG8 knockdown exhibited an opposite role in reducing BLM-induced pulmonary fibrosis. With regard to the mechanism, SNHG8 was then revealed to act as a competing endogenous RNA (ceRNA) for microRNA (miR)-4701-5p in regulating Mucin 5B (MUC5B) expression. Furthermore, the interactions between SNHG8 and miR-4701-5p, between miR-4701-5p and MUC5B, and between SNHG8 and MUC5B on the influence of fibrosis-related indicators were confirmed, respectively. In addition, SNHG8 overexpression enhanced the levels of transforming growth factor (TGF)-β1 and phosphorylation Smad2/3 (-Smad2/3), which was suppressed by SNHG8 knockdown in BLM-induced A549 cells. Moreover, miR-4701-5p inhibitor-induced elevation of TGF-β1 and -Smad2/3 was significantly suppressed by SNHG8 knockdown. In conclusion, SNHG8 knockdown attenuated pulmonary fibrosis progression by regulating miR-4701-5p/MUC5B axis, which might be associated with the modulation of TGF-β1/Smad2/3 signaling. These findings reveal that lncRNA SNHG8 may become a potential target for the treatment of IPF.

Citing Articles

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PMID: 39433746 PMC: 11494106. DOI: 10.1038/s41420-024-02170-5.

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