Function and mechanism of microRNA-127 in pancreatic carcinoma

Abstract

Objective To explore the molecular function of microRNA-127 (microRNA, miR-127) in regulating pancreatic cancer development in vitro. Methods Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) was performed to evaluate endogenous miR-127 expression in in vitro pancreatic cancer cell lines and in vivo clinical samples of pancreatic carcinoma. Lentiviral technology was applied to overexpress miR-127 in capan-1 and PANC-1 cells. Pancreatic cancer proliferation, cell-cycle progression and invasion were assessed in vitro. Dual-luciferase reporter assay and RT-qPCR were performed to assess the downstream target gene of miR-127 in pancreatic cancer, human bcl-2 associated athanogene 5 (BAG5). BAG5 was subsequently upregulated in miR-127-overexpressed capan-1 and PANC-1 cells to evaluate its effect on pancreatic cancer progression. Results Compared with normal pancreatic duct cells hTERT-HPNE, the expression of miR-127 in a variety of pancreatic cancer cell lines was increased from (30.0±8.1)% to (72.0±12.3)% (P=0.004) respectively, and that in pancreatic tumors was (48.0±18.2)% (P=0.003) as compared with normal pancreatic tissues around the tumor. miR-127 could inhibit cancer cells proliferation (P=0.003), arrest cell cycle in G1 period, increase the ratio of Canpan-1 cells in G1 period from (49.0±6.2)% to (62.0±4.3)% (P=0.010), increase PANC-1 cells from (56.0±7.1)% to (68.0±4.1)% (P=0.015) and decrease invasion ability (P=0.004). Human BAG5 was confirmed to be the downstream target of miR-127 in pancreatic cancer. Forced overexpression of BAG5 in capan-1 and PANC-1 cells reversed the tumor-suppressing effect of miR-127 on cancer development (P=0.000). Conclusion miR-127 is downregulated and acts as a tumor suppressor in pancreatic carcinoma. The functional regulation of miR-127 in pancreatic carcinoma is very likely through the inverse correlation of its downstream target gene of BAG5. Key words: Pancreatic carcinoma; MicroRNA-127; Bcl-2 associated athanogene 5; Proliferation; Invasion; Transfer