Long non‐coding RNA SNHG16 regulates human aortic smooth muscle cell proliferation and migration via sponging miR‐205 and modulating Smad2

Abstract

The present study investigated the role of long non‐coding RNA (lncRNA) small nucleolar RNA host gene 16 (SNHG16) in the human aortic smooth muscle cell (HASMC) proliferation and migration and explored the potential link between SNHG16 and atherosclerosis. Our results showed that platelet‐derived growth factor (PDGF)‐bb treatment promoted cell proliferation and migration with concurrent up‐regulation of SNHG16 in HASMCs. Small nucleolar RNA host gene 16 overexpression promoted HASMC proliferation and migration, while SNHG16 knockdown suppressed cell proliferation and migration in PDGF‐bb‐stimulated HASMCs. The bioinformatic analyses showed that SNHG16 possessed the complementary binding sequence with miR‐205, where the interaction was confirmed by luciferase reporter assay and RNA pull‐down assay in HASMCs, and SNHG16 inversely regulated miR‐205 expression. MiR‐205 overexpression attenuated the enhanced effects of PDGF‐bb treatment on HASMC proliferation and migration. Moreover, Smad2 was targeted and inversely regulated by miR‐205, while being positively regulated by SNHG16 in HASMCs. Smad2 knockdown attenuated PDGF‐bb‐mediated actions on HASMC proliferation and migration. Both miR‐205 overexpression and Smad2 knockdown partially reversed the effects of SNHG16 overexpression on HASMC proliferation and migration. Moreover, SNHG16 and Smad2 mRNA were up‐regulated, while miR‐205 was down‐regulated in the plasma from patients with atherosclerosis. Small nucleolar RNA host gene 16 expression was inversely correlated with miR‐205 expression and positively correlated with Smad2 expression in the plasma from atherosclerotic patients. In conclusion, our data showed the up‐regulation of SNHG16 in pathogenic‐stimulated HASMCs and clinical samples from atherosclerotic patients. Small nucleolar RNA host gene 16 regulated HASMC proliferation and migration possibly via regulating Smad2 expression by acting as a competing endogenous RNA for miR‐205.

miR‐142‐5p protects against osteoarthritis through competing with lncRNA XIST

“…Mechanistically, recent studies show that several lncRNAs or circRNAs, harboring miRNA‐binding sites, are capable of functioning as competing endogenous RNAs (ceRNAs) to naturally sequester miRNA away from target mRNA and competitively block the inhibitory impact of miRNA on mRNA . As explained previously, SNHG16 can block the inhibition of miR‐205 on Smad2 expression in aortic smooth muscle cell proliferation and migration . LncRNA NR_038323 suppresses the activity of miR‐324‐3p to up‐regulate DUSP1 with respect to suppressing renal fibrosis in diabetic nephropathy .…”

“…18 As explained previously, SNHG16 can block the inhibition of miR-205 on Smad2 expression in aortic smooth muscle cell proliferation and migration. 19 LncRNA NR_038323 suppresses the activity of miR-324-3p to up-regulate DUSP1 with respect to suppressing renal fibrosis in diabetic nephropathy. 20 LncRNA FLVCR1-AS1 attenuates the suppression of miR-513 on YAP1 activity in ovarian cancer.…”

Unveiling the ups and downs of miR-205 in physiology and cancer: transcriptional and post-transcriptional mechanisms

“…These studies revealed that SNHG16, by acting as endogenous sponge of miR-205, upregulates ZEB1 and enhances proliferation of osteosarcoma cells 72 . Similarly, SNHG16 was found to act as miR-205 sponge in the cardiovascular context, where reduced levels of miR-205 are related to increased proliferation and migration of aortic smooth muscle cells, suggesting a link with atherosclerosis 73 . In ovarian cancer, an increase of miR-205 levels are related to a reduction of its lncRNA sponge LINC01133.…”

Long non-coding RNA SNHG16 contributes to progression of carotid atherosclerosis by regulating miR-30c-5p/ADAM10 axis

“…Lnc-SNHG16, located at 17q25.1 gene, was identified as an oncogenic lncRNA in various types of cancer [36,37]. Importantly, in a recent publication, lnc-SNHG16 was verified to be abnormally increased and exacerbated the progression of atherosclerosis through triggering hASMCs proliferation and migration [38]. However, the underlying mechanism of lnc-SNHG16 in CAS still needs further clarification.…”