MiR-10a-5p targets TFAP2C to promote gemcitabine resistance in pancreatic ductal adenocarcinoma

Abstract

Abstract Background By regulating target genes, microRNAs play essential roles in carcinogenesis and drug resistance in human pancreatic ductal adenocarcinoma (PDAC). Previous studies have shown that microRNA-10a-5p (miR-10a-5p) is overexpressed in PDAC and acts as an oncogene to promote the metastatic behavior of PDAC cells. However, the role of miR-10a-5p in PDAC chemoresistance remains unclear. Methods The effects of miR-10a-5p on biological behaviors were analyzed. MiR-10a-5p and TFAP2C levels in tissues were detected, and the clinical value was evaluated. Results We found that miR-10a-5p is up-regulated in gemcitabine-resistant PDAC cells and enhances PDAC cell gemcitabine resistance in vitro and vivo. Meanwhile, we also determined that miR-10a-5p promotes the migratory and invasive ability of PDAC cells. Next, we confirmed that transcription factor activating protein 2 gamma (TFAP2C) is a target of miR-10a-5p, and TFAP2C overexpression resensitizes PDAC cells to gemcitabine, which is initiated by miR-10a-5p. Further studies revealed that TFAP2C also decreased PDAC cell migration and invasion capability. Finally, survival analysis demonstrated that high miR-10a-5p expression levels and low TFAP2C expression levels were both independent adverse prognostic factors in patients with PDAC. Conclusion Together, these results indicate that miR-10a-5p/TFAP2C may be new therapeutic target and prognostic marker in PDAC.

Keywords

• miR-10a-5p
• TFAP2C
• PDAC
• Chemoresistance
• Prognosis