LncRNA GNAS-AS1 knockdown inhibits keloid cells growth by mediating the miR-188-5p/RUNX2 axis

• Published in: Molecular and cellular biochemistry 2023-04, Vol.478 (4), p.707-719
• Main Authors: Liu, Yun, Li, Lei, Wang, Jia-Yao, Gao, Fei, Lin, Xia, Lin, Shi-Shuai, Qiu, Zhi-Yang, Liang, Zun-Hong
• Format: Article
• Language: English
• Subjects: Assaying; Binding sites; Biochemistry; Bioinformatics; Biomedical and Life Sciences; Breast cancer; Cancer Research; Carcinogenesis; Carcinogens; Cardiology; Cbfa-1 protein; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Cholecystokinin; Chromogranins - genetics; Chromogranins - metabolism; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Dermis; Fibroblasts; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Growth; GTP-Binding Protein alpha Subunits, Gs - genetics; GTP-Binding Protein alpha Subunits, Gs - metabolism; Hospitals; Humans; Keloid - genetics; Life Sciences; Medical Biochemistry; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Non-coding RNA; Plasmids; Plastic surgery; Proteins; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Scars; Skin; Transcription factors; Tumors; Wound healing
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-022-04538-6

Keloid is a common dermis tumor, occurring repeatedly, affecting the quality of patients’ life. Long non-coding RNAs (lncRNAs) have crucial regulatory capacities in skin scarring formation and subsequent scar carcinogenesis. The intention of this study was to investigate the mechanism and function of GNAS antisense-1 (GNAS-AS1) in keloids. Clinical samples were collected to evaluate the expression of GNAS-AS1, RUNX2, and miR-188-5p by qRT-PCR. The proliferation, migration, and invasion of HKF cells were detected by CCK-8, wound healing, and Transwell assays. The expression levels of mRNA and protein were examined through qRT-PCR and Western blot assay. Luciferase reporter assay was used to identify the binding relationship among GNAS-AS1, miR-188-5p, and Runt-related transcription factor 2 (RUNX2). GNAS-AS1 and RUNX2 expressions were remarkably enhanced, and miR-188-5p expression was decreased in keloid clinical tissues and HKF cells. GNAS-AS1 overexpression promoted cells proliferation, migration, and invasion, while GNAS-AS1 knockdown had the opposite trend. Furthermore, overexpression of GNAS-AS1 reversed the inhibitory effect of 5-FU on cell proliferation, migration, and invasion. MiR-188-5p inhibition or RUNX2 overexpression could enhance the proliferation, migration, and invasion of HKF cells. GNAS-AS1 targeted miR-188-5p to regulate RUNX2 expression. In addition, the inhibition effects of GNAS-AS1 knockdown on HKF cells could be reversed by inhibition of miR-188-5p or overexpression of RUNX2, while RUNX2 overexpression eliminated the suppressive efficaciousness of miR-188-5p mimics on HKF cells growth. GNAS-AS1 knockdown could regulate the miR-188-5p/RUNX2 signaling axis to inhibit the growth and migration in keloid cells. It is suggested that GNAS-AS1 may become a new target for the prevention and treatment of keloid.