Down regulation of miR-33a is involved in gemcitabine chemoresistance in human pancreatic cancer / 中国癌症杂志

ABSTRACT

Background and purpose:Pancreatic cancer is one of the most deadly human malignant neoplasms. Resistance to chemotherapeutic drugs is a major reason responsible for poor prognosis in the treatment of pancreatic cancer patients. MicroRNA (miRNA, miR) is a family of small non-coding RNA molecules, dysregulated miRNA is associated with various tumor biological function. miR-33a has been widely reported as a metabolism-related miRNA, while its relationship with drug resistance has little understand. This study was focused on the effect of miR-33a on gemcitabine chemoresistance in pancreatic cancer to bring the novel theoretical basis to chemotherapy for pancreatic cancer.Methods:In situ hybridization and Real-time PCR were used to analyze the miR-33a expressions in pancreatic cancer tissue sample and cell lines, respectively. Cell counting kit 8 (CCK-8) assay was used to calculate the IC50 value of different pancreatic cancer cells.Results:miR-33a was down-regulated in pancreatic cancer tissue and cell lines compared with para-cancerous tissues and normal HEK293T cells. Moreover, miR-33a over expression not only could enhance the chemosensitivity to gemcitabine in pancreatic cancer cells, but also rescue the gemcitabine resistance in pancreatic cancer cells.Conclusion:Down regulation of miR-33a in pancreatic cancer decreases the chemosensitivity to gemcitabine, resulting in development of acquired gemcitabine chemoresistance. It provides the theoretical basis to develop a new molecular targeted drug to combine with chemotherapy for pancreatic cancer.