Liu Qiang, Zou Ran, Zhou Rouxi, Gong Chaofan, Wang Zhifei, Cai Tao, Tan Chaochao, Fang Jiasheng
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
Department of Neurosurgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
J Cell Biochem. 2015 Jul;116(7):1213-21. doi: 10.1002/jcb.25073.
The critical role of microRNAs in cancer development has been extensively described. miRNAs are both specific markers and putative therapy targets. miR-155 has been identified to be an oncomiRNA and is highly expressed in several solid cancers, including glioblastoma. In this study, we found that miR-155 is a good potential therapy target. Knockdown of miR-155 sensitizes glioma cells to the chemotherapy of temozolomide (TMZ) by targeting the p38 isoforms mitogen-activated protein kinase 13 [MAPK13, also known as p38 MAPKδ or stress-activated protein kinase 4 (SAPK4)] and MAPK14 (also known as p38 MAPKα). As tumor suppressor genes, MAPK13 and MAPK14 play important roles in lowering the accumulation of reactive oxygen species (ROS), inducing cell apoptosis, and slowing the progression of cancer. Knockdown of miR-155 enhanced the anticancer effect of TMZ on glioma by targeting the MAPK13 and MAPK14-mediated oxidative stress and apoptosis, but did not affect the secretion of MMP2 and MMP9.
微小RNA在癌症发展中的关键作用已被广泛描述。微小RNA既是特异性标志物，也是潜在的治疗靶点。miR-155已被确定为一种癌基因miRNA，在包括胶质母细胞瘤在内的几种实体癌中高度表达。在本研究中，我们发现miR-155是一个良好的潜在治疗靶点。通过靶向有丝分裂原激活蛋白激酶13 [MAPK13，也称为p38 MAPKδ或应激激活蛋白激酶4 (SAPK4)]和MAPK14（也称为p38 MAPKα）的p38亚型，敲低miR-155可使胶质瘤细胞对替莫唑胺（TMZ）化疗敏感。作为肿瘤抑制基因，MAPK13和MAPK14在降低活性氧（ROS）积累、诱导细胞凋亡以及减缓癌症进展中发挥重要作用。敲低miR-155通过靶向MAPK13和MAPK14介导的氧化应激和凋亡增强了TMZ对胶质瘤的抗癌作用，但不影响MMP2和MMP9的分泌。
