MicroRNA-221 induces autophagy through suppressing HDAC6 expression and promoting apoptosis in pancreatic cancer

摘要

Pancreatic cancer is an aggressive type of cancer with a poor prognosis, short survival rate and high mortality. Therefore, understanding the molecular mechanism underlying the aggressive growth of pancreatic cancer is of importance. An increasing number of studies suggest that numerous microRNAs (miRNAs/miRs) are associated with the tumorigenesis, progression and prognosis of tumors. In a recent study by the present authors, it was revealed that the expression of miR-221 was significantly downregulated in highly aggressive pancreatic cancer cells compared with weakly aggressive pancreatic cancer cells. In addition, miR-221 has been suggested as a novel tumor-associated miRNA, as it is involved in apoptosis, invasion, metastasis and autophagy of tumor cells. However, the function of miR-221 in pancreatic cancer remains yet to be investigated. In the present study, it was revealed that transfection with miR-221 mimic was able to significantly induce apoptosis and autophagy in pancreatic cancer cells compared with the negative control. The protein deacetylase histone deacetylase-6 (HDAC6) has emerged to be an important component in the cellular management of protein aggregates. Studies suggest that HDAC6 serves a function in the clearance of aggresomes, thereby implying a functional association between HDAC6 and autophagy. In the present study, it was revealed that transfection with miR-221 mimic was able to suppress the protein expression of HDAC6 in pancreatic cancer cells compared with the negative control. Immunofluorescence data suggested that the inhibition of HDAC6 was able to induce autophagy in pancreatic cancer cells. Additionally, the results of the present study suggest that the downregulation of miR-221 expression may serve an oncogenic function in the apoptosis and autophagy of pancreatic cancer cells by inducing the expression of HDAC6.