MiR-4282 contributes to inhibit pancreatic cancer metastasis by negatively interacting with ABCB5.

Abstract

To explore the regulatory mechanism of microRNA-4282 (miR-4282) on influencing pancreatic cancer progression by targeting ABCB5. MiR-4282 and ABCB5 levels in 58 cases of pancreatic cancer and paracancerous tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The influences of miR-4282 on pathological indicators and prognosis in pancreatic cancer patients were analyzed. MiR-4282 overexpression model was established in PANC-1 and BxPC-3 cells by transfection of miR-4282 mimic. Transwell and wound healing assay were conducted to illustrate the role of miR-4282 in influencing cell functions of pancreatic cancer. Bioinformatics analysis and Dual-Luciferase reporter assay were carried out to ascertain the interaction between miR-4282 and ABCB5. MiR-4282 was downregulated in pancreatic cancer samples. Low level of miR-4282 predicted high incidences of lymphatic metastasis and distant metastasis, as well as poor prognosis in pancreatic cancer patients. Overexpression of miR-4282 remarkably inhibited migratory ability in PANC-1 and BxPC-3 cells. MiR-4282 was targeted by ABCB5 through specific binding sites. In pancreatic cancer tissues, ABCB5 level was negatively correlated to that of miR-4282. Overexpression of ABCB5 could abolish the inhibitory effects of overexpressed miR-4282 on the malignant progression of pancreatic cancer. MiR-4282 is able to inhibit the migratory ability in pancreatic cancer cells by negatively targeting ABCB5, which may become a promising pancreatic cancer biomarker.