miR-30d Modulates Sensitivity of Anaplastic Thyroid Cancer Cells to Cisplatin via suppressing Beclin1-midiated Autophagy
Macroautophagy (also known as autophagy) is a main route for sequestration and digestion of cytoplasm in acidic compartments in order for cancer cells to survive from nutrient depletion, chemotherapy or other insults.In the present study, we characterized the role of miR-30d in the crosstalk between autophagy and apoptosis, which determines the sensitivity of anaplastic thyroid cancer (ATC) cells to cisplatin.We found that treatment with cisplatin caused activation of autophagy in ATC cell lines, SW1736 and 8305C.We further demonstrated that forced expression of miR-30d significantly reduced cisplatin-induced autophagy, resulting in increased cisplatininduced cytotoxicity.Moreover, inhibition of autophagy and sensitization to cisplatin by forced expression of miR-30d were accompanied by induction of apoptosis.To confirm that the sensitizing effect of miR-30d on the cytotoxicity of cisplatin was attributed to suppression of autophagy, we assessed the effects of the autophagy inhibitors 3-MA and chloroquine.Treatment with 3-MA and chloroquine strongly increased cisplatin-induced apoptosis, indicating that blockade of autophagy indeed renders ATC cells sensitivity to cisplatin.Finally, an in vivo ATC implantation mouse model clearly showed that elevation of miR-30d significantly enhanced cisplatininduced apotosis in implanted tumor cells.By using molecular and biochemistry assays, we found that the autophagy-related gene Beclinl, can be directly regulated by miR-30d in cancer cells.Our results not only revealed a new mechanism determining cisplatin sensitivity, but also identified miR-30d as a novel autophagy regulator which can target Beclinl.Thus, that increasing miR-30d level maybe exploited a novel approach to enhance the efficacy ofcisplatin against ATC or other types of malignancies.
miR-30d autophagy apoptosis Beelin1 cisplatin Anaplastic thyroid cancer
Zhang Y Zhu H Yang JM Yang WQ Zhang L Zhou L Ren YJ Ren XC Ming ZJ Chen B Wang JR
Department of Pharmacology, College of Pharmaceutical Sciences, Cyrus Tang Hematology Center, Affili Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, 195 Little Albany Department of Pharmacology, College of Pharmaceutical Sciences, Cyrus Tang Hematology Center, Affili Pharmacology and The Penn State Hershey Cancer Institute, The Pennsylvania State University College
国内会议
江苏省药理学会青年工作委员会成立大会暨药理学科青年科技创新学术研讨会
苏州
英文
175-176
2013-05-24（万方平台首次上网日期，不代表论文的发表时间）