LncRNA TP73-AS1 sponges miR-141-3p to promote the migration and invasion of pancreatic cancer cells through the up-regulation of BDH2

• Published in: Bioscience reports 2019-03, Vol.39 (3)
• Main Authors: Cui, Xian-Ping, Wang, Chuan-Xi, Wang, Zhi-Yi, Li, Jian, Tan, Ya-Wen, Gu, Song-Tao, Qin, Cheng-Kun
• Format: Article
• Language: English
• Subjects: Cell Line, Tumor; Cell Movement - genetics; Female; Gene Expression Regulation, Neoplastic; Humans; Hydroxybutyrate Dehydrogenase - genetics; Hydroxybutyrate Dehydrogenase - metabolism; Kaplan-Meier Estimate; Male; MicroRNAs - genetics; Middle Aged; Neoplasm Invasiveness; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; RNA Interference; RNA, Long Noncoding - genetics; Up-Regulation
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/BSR20181937

LncRNA TP73 antisense RNA 1T (TP73-AS1) plays an important role in human malignancies. However, the levels of TP73-AS1 and its functional mechanisms in pancreatic cancer metastasis remain unknown, and the clinical significance of TP73-AS1 in human pancreatic cancer is also unclear. In the present study, the levels of TP73-AS1 and its candidate target miR-141 in pancreatic cancer and adjacent normal tissue were detected using qRT-PCR. The association between TP73-AS1 levels and the clinicopathologic characteristics of pancreatic cancer patients were analyzed. The relationship between TP73-AS1 and miR-141, and miR-141 and its candidate target 3-hydroxybutyrate dehydrogenase type 2 (BDH2) was confirmed using dual-luciferase reporter assays. TP73-AS1 and/or miR-141 were knocked down using siRNA or an inhibitor in pancreatic cancer cells and cell migration and invasion then examined. The results showed that TP73-AS1 was up-regulated in pancreatic cancer tissue and cell lines. High levels of TP73-AS1 were correlated with poor clinicopathological characteristics and shorter overall survival. MiR-141 was a direct target for TP73-AS1, while BDH2 was a direct target for miR-141. The knockdown of TP73-AS1 significantly inhibited the migration and invasion of pancreatic cancer cells, while the miR-141 inhibitor significantly restored the migration and invasion. Therefore, TP73-AS1 positively regulated BDH2 expression by sponging miR-141. These findings suggest that TP73-AS1 serves as an oncogene and promotes the metastasis of pancreatic cancer. Moreover, TP73-AS1 could serve as a predictor and a potential drug biotarget for pancreatic cancer.