Long non-coding RNA H19 promotes the proliferation, migration and invasion while inhibits apoptosis of hypertrophic scarring fibroblasts by targeting miR-3187-3p/GAB1 axis.

BACKGROUND: It had been reported that long non-coding RNA (lncRNA) H19 was associated with the proliferation of fibroblasts. However, the regulatory mechanism of H19 remains unclear. Thus, the study was designed to explore the underlying mechanism of H19 in the process of Hypertrophic scarring (HS). METHODS: The expression levels of H19, miR-3187-3p, and growth factor receptor binding 2-associated binding protein 1 (GAB1) in HS tissues and HS fibroblasts were measured by real-time quantitative polymerase chain reaction (RT-qPCR) assay. The biological behaviors of HS fibroblasts, such as cell proliferation, apoptosis, migration, and invasion were assessed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT), colony formation, flow cytometry, and transwell assays, respectively. The protein expression level was quantified by western blot assay. The interaction association between miR-3187-3p and H19 or GAB1 was predicted by Starbase database analysis and confirmed by dual-luciferase reporter assay, respectively. RESULTS: H19 was significantly increased in HS tissues and HS fibroblasts. Loss-of-functional experiments revealed that knockdown of H19 inhibited the development of HS. Moreover, silencing of H19 impeded the proliferation, migration, and invasion, while enhanced apoptosis of HS fibroblasts by increasing miR-3187-3p expression. In addition, overexpression of GAB1 could abolish miR-3187-3p overexpression-induced effects on cell proliferation, apoptosis, migration, and invasion of HS fibroblasts. Mechanistically, H19 could act as a sponge of miR-3187-3p to upregulate the expression of GAB1 in HS fibroblasts. CONCLUSION: Collectively, our results revealed that H19 promoted the proliferation, migration, and invasion, while impeded apoptosis of HS fibroblasts by targeting miR-3187-3p/GAB1 axis.

Long non-coding RNA LINC01116 accelerates the progression of keloid formation by regulating miR-203/SMAD5 axis.

BACKGROUND: Emerging evidence reveals the importance of long non-coding RNAs (lncRNAs) in the development and progression of keloid formation. However, the roles and molecular mechanism of lncRNA LINC01116 in the progression of keloid formation remain largely unknown. METHODS: The expression levels of LINC01116, microRNA-203 (miR-203) and SMAD family member 5 (SMAD5) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell proliferation, migration and invasion were detected by Cell counting Kit-8 (CCK-8) assay and transwell assay. Flow cytometry and western blot assay were used to examine cell apoptosis and extracellular matrix (ECM) production. The interaction between miR-203 and LINC01116 or SMAD5 was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) and RNA pull-down assays. RESULTS: LINC01116 and SMAD5 were upregulated while miR-203 was downregulated in keloid tissues and keloid fibroblasts. LINC01116 knockdown suppressed the proliferation, migration, invasion, and ECM production but induced apoptosis in keloid fibroblasts through enhancing miR-203 and inhibiting SMAD5. Moreover, SMAD5 was identified as a direct target of miR-203 and miR-203 could directly bind to LINC01116. Besides, LINC01116 regulated SMAD5 expression by targeting miR-203. CONCLUSION: Downregulation of LINC01116 inhibited the progression of keloid formation by regulating miR-203/SMAD5 axis, which might provide a novel target for keloid therapy.

The effects of NONRATT021972 lncRNA siRNA on PC12 neuronal injury mediated by P2X7 receptor after exposure to oxygen-glucose deprivation.

Adenosine triphosphate (ATP) participates in signal transmission by acting on P2X receptors, and the P2X7 receptor is involved in the pathophysiological changes of ischemic injury. The PC12 cell line is a popular model system to study sympathetic neuronal function. Long noncoding RNAs (lncRNAs) are highly expressed in the nervous system and serve as regulatory RNAs. In this study, the effects of NONRATT021972 lncRNA siRNA on P2X7-mediated PC12 neuronal injury after exposure to oxygen-glucose deprivation (OGD) were investigated. Our results showed that the viability of PC12 cells cultured with OGD or the P2X7 agonist BzATP was significantly decreased. Treatment with NONRATT021972 siRNA reversed the decreased viability of PC12 cells under OGD conditions. The upregulated P2X7 mRNA and protein levels in PC12 cells under OGD conditions or BzATP treatment were significantly decreased when pretreated with NONRATT021972 siRNA. Moreover, NONRATT021972 siRNA treatment effectively suppressed the increase in [Ca(2+)]i induced by OGD or P2X7 agonists (ATP or BzATP) in PC12 cells. Therefore, treatment with NONRATT021972 siRNA may decrease sympathetic neuronal injury induced by ischemia.