HNF1A/CASC2 regulates pancreatic cancer cell proliferation through PTEN/Akt signaling†

Pancreatic cancer (PC) has a high mortality rate in all cancers worldwide. According to recent studies, long non-coding RNA-CASC2 is involved in the development and progression of many malignant tumors; in the present study, we demonstrated that lncRNA-CASC2 was specifically downregulated in PC tissues and cell lines, and a lower CASC2 expression in PC was related with a poorer prognosis. CASC2 suppressed PC cell proliferation. Hepatocyte nuclear factor 1 alpha (HNF1A) is a transcription factor known to regulate pancreatic differentiation and maintain the homeostasis of endocrine pancreas. Recently, HNF1A is considered to be a possible tumor suppressor in PC. In the present study, we observed that HNF1A positively regulated CASC2 expression. Through Luciferase assays, we demonstrated that CASC2 gene possessed a HNF1A-responsive element (CASC2-HNF1A RE); HNF1A could promote CASC2 expression through direct binding to CASC2-HNF1A RE. Further, PTEN/Akt signaling was involved in HNF1A regulation of CASC2. Finally, we evaluated the expression level of HNF1A in PC tissues; lower HNF1A expression was correlated with shorter overall survival (OS) in patients with PC. Taken together, these findings will shed light to the role and mechanism of HNF1A/CASC2 in regulating PC cells proliferation through PTEN/Akt signaling. CASC2 may serve as a potential therapeutic target in PC in the future. This article is protected by copyright. All rights reserved