MicroRNA-30a downregulation contributes to chemoresistance of osteosarcoma cells through activating Beclin-1-mediated autophagy.

作者: RUIDA XU , SHUZHONG LIU , HAIHONG CHEN , LIFENG LAO

DOI: 10.3892/OR.2015.4497

关键词:

摘要: Abstract Autophagy has been recognized as an important element of tumor cell migration, invasion, and chemo-resistance, our previous results showed that Beclin-1-mediated autophagy contributed to osteosarcoma chemoresistance. However, the regulating mechanism is still unclear. In this study, aim was clarify microRNA (miRNA)-related mechanisms underlying followed by chemotherapy in osteosarcoma. First, miRNA screening using qRT-PCR identified miR-30a significantly reduced Dox-resistant cells. Second, activity increased while expression after agents indicated enhanced Beclin-1, conversion microtubule-associated protein LC3-I LC3-II. Furthermore, overexpression promoted chemotherapy-induced apoptosis responding chemotherapy. Moreover, rapamycin, promoter able partly reverse effect Luciferase reporter assay directly binds 3'-UTR Beclin-1 gene, which further confirmed chemoresistance via suppressing autophagy. Collectively these indicate its downstream target gene can be used treatment chemo-resistance future.

参考文章(30)
L. Y Zhao, X. P Wen, H. L Ma, C. X Dang, W Zhang, MiR-30a suppresses non-small cell lung cancer progression through AKT signaling pathway by targeting IGF1R Cellular and Molecular Biology. ,vol. 61, pp. 78- 85 ,(2015)
Linzhi Xiao, Chaoxia Liu, Xiaomin Ran, Ping Zhou, Juan Yang, Keqiang Zhang, MiR-218 inhibits HMGB1-mediated autophagy in endometrial carcinoma cells during chemotherapy International Journal of Clinical and Experimental Pathology. ,vol. 8, pp. 6617- 6626 ,(2015)
Wenbo Wang, Hui Jin, MicroRNA-539 suppresses osteosarcoma cell invasion and migration in vitro and targeting Matrix metallopeptidase-8 International Journal of Clinical and Experimental Pathology. ,vol. 8, pp. 8075- 8082 ,(2015)
HAIWEI WU, SHENGYUN HUANG, ZHANWEI CHEN, WENLEI LIU, XIAOQING ZHOU, DONGSHENG ZHANG, Hypoxia-induced autophagy contributes to the invasion of salivary adenoid cystic carcinoma through the HIF-1α/BNIP3 signaling pathway. Molecular Medicine Reports. ,vol. 12, pp. 6467- 6474 ,(2015) , 10.3892/MMR.2015.4255
Yunhua He, Yuchan Wang, Hong Liu, Xiaohong Xu, Song He, Jie Tang, Yuejiao Huang, Xiaobing Miao, Yaxun Wu, Qiru Wang, Chun Cheng, Pyruvate kinase isoform M2 (PKM2) participates in multiple myeloma cell proliferation, adhesion and chemoresistance Leukemia Research. ,vol. 39, pp. 1428- 1436 ,(2015) , 10.1016/J.LEUKRES.2015.09.019
Zhi Chen, Tongjian Wang, Zhen Liu, Guangyu Zhang, Jinhe Wang, Shisheng Feng, Jianqin Liang, Inhibition of Autophagy by MiR-30A Induced by Mycobacteria tuberculosis as a Possible Mechanism of Immune Escape in Human Macrophages Japanese Journal of Infectious Diseases. ,vol. 68, pp. 420- 424 ,(2015) , 10.7883/YOKEN.JJID.2014.466
Zhenyou Zou, Linping Wu, Hanying Ding, Yang Wang, Yaqin Zhang, Xuejiao Chen, Xi Chen, Chen-Yu Zhang, Qipeng Zhang, Ke Zen, MicroRNA-30a Sensitizes Tumor Cells to cis-Platinum via Suppressing Beclin 1-mediated Autophagy Journal of Biological Chemistry. ,vol. 287, pp. 4148- 4156 ,(2012) , 10.1074/JBC.M111.307405
Jean-Pierre Gillet, Michael M. Gottesman, Overcoming multidrug resistance in cancer: 35 years after the discovery of ABCB1 Drug Resistance Updates. ,vol. 15, pp. 2- 4 ,(2012) , 10.1016/J.DRUP.2012.03.001
Anja Luetke, Paul A. Meyers, Ian Lewis, Heribert Juergens, Osteosarcoma treatment - where do we stand? A state of the art review. Cancer Treatment Reviews. ,vol. 40, pp. 523- 532 ,(2014) , 10.1016/J.CTRV.2013.11.006