HMGA2-AS1 promotes the growth and cisplatin resistance in esophageal squamous cell carcinoma by enhancing HMGA2-dependent transcription of Snail2

Drug resistance restrains the efficacy of platinum-based chemotherapy against esophageal squamous cell carcinoma (ESCC). Long noncoding RNAs (lncRNAs) play crucial roles in various cancers. In this study, we conducted bioinformatical analysis to search for key lncRNAs involved in ESCC progression. Experimental validations focused on a candidate lncRNA, HMGA2-AS1. The roles of the lncRNA HMGA2-AS1 in ESCC growth and cisplatin resistance were explored. The clinical significance of HMGA2-AS1 in ESCC was also determined. Our data demonstrated that HMGA2-AS1 was significantly upregulated in ESCC relative to adjacent normal tissues and correlated with tumor size (p = 0.0035) and tumor stage (p = 0.0001). Knockdown of HMGA2-AS1 suppressed the proliferation and colony formation and increased cisplatin sensitivity in ESCC cells. In vivo tumorigenic studies showed that depletion of HMGA2-AS1 impaired tumorigenesis of ESCC cells. Enforced expression of HMGA2-AS1 promoted ESCC proliferation and cisplatin resistance. HMGA2-AS1 interacted with HMGA2 protein in the nucleus of ESCC cells, promoting HMGA2-dependent transactivation of Snail2. Silencing of HMGA2 abrogated HMGA2-AS1-induced proliferation and cisplatin resistance in ESCC cells, which were rescued by overexpression of Snail2. In conclusion, our results highlight the importance of HMGA2-AS1 in ESCC growth and cisplatin resistance. HMGA2-AS1-induced aggressive phenotype in ESCC depends on the interaction with HMGA2. HMGA2-AS1 may serve as a potential therapeutic target for ESCC.