Inhibition of Long Noncoding RNA SNHG20 Improves Angiotensin II-Induced Cardiac Fibrosis and Hypertrophy by Regulating the MicroRNA 335/Galectin-3 Axis

ABSTRACT

Cardiac fibrosis is a hallmark of various heart diseases and ultimately leads to heart failure. Although long noncoding RNA (lncRNA) SNHG20 has been reported to play important roles in various cancers, its function in cardiac fibrosis remains unclear. The expression of SNHG20 and microRNA 335 (miR-335) in heart tissues of angiotensin II-induced mice and angiotensin II-stimulated mouse cardiomyocyte cell line HL-1 were detected by quantitative real-time PCR (qRT-PCR). Cell viability was evaluated by cell counting kit-8 assay. The expression of galectin-3, fibrosis-related proteins (fibronectin, collagen IaI, and α-SMA), and apoptosis-related proteins [cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP)] was detected by Western blotting. Bioinformatics prediction, luciferase reporter assay, and RNA pulldown assay were performed to determine the relationship between SNHG20 and miR-335 as well as miR-335 and Galectin-3. Gain- and loss-function assays were performed to determine the role of SNHG20/miR-335/Galectin-3 in cardiac fibrosis. SNHG20 was significantly upregulated and miR-335 was downregulated in heart tissues of angiotensin II-treated mice and angiotensin II-stimulated HL-1 cells. Downregulation of SNHG20 effectively enhanced cell viability and decreased cell size of HL-1 cells and the expression levels of fibrosis-related proteins (fibronectin, collagen IaI, and α-SMA) and apoptosis-related proteins (cleaved caspase-3 and cleaved PARP), which were induced by angiotensin II treatment. Furthermore, SNHG20 elevated the expression levels of Galectin-3 by directly regulating miR-335. Our study revealed that downregulation of SNHG20 improved angiotensin II-induced cardiac fibrosis by targeting the miR-335/Galectin-3 axis, suggesting that SNHG20 is a therapeutic target for cardiac fibrosis and hypertrophy.

KEYWORDS:

• cardiac fibrosis
• SNHG20
• miR-335
• Galectin-3

SUPPLEMENTAL MATERIAL

Supplemental material is available online only.

ACKNOWLEDGMENTS

This work was supported by a grant from the National Natural Science Foundation of China (81570358), Health and Family Planning Commission of Shanghai Pudong New District, China (PWZxq2017-01 and PWYgy2018-03), and Health and Family Planning Commission of Shanghai, China (ZK2019B25).