作者机构：
[张波] School of Medicine, Hunan University of Chinese Medicine, Changsha 410208;[张波; 张健] Key Laboratory of Protein Chemistry and Developmental Biology, Ministry of Education, School of Life Sciences, Hunan Normal University, Changsha 410081, China;[周芳亮; 严杰; 卢芳国] School of Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
摘要：
肿瘤干细胞(Cancer stem cells, CSCs)是肿瘤组织中一小部分具有自我更新和致瘤性的细胞, 具有特殊的耐药机制, 与肿瘤的复发和治疗失败关系密切。微小RNA(microRNAs, miRNAs)是一类长度约为19~25个核苷酸的内源性非编码单链RNA, 能够通过调控相关靶基因的表达, 参与调控肿瘤干细胞增殖、凋亡、上皮-间质转化等重要的生命过程, 引起CSCs对化疗药物产生原发性多药耐药性。本论文就miRNAs在调控CSCs多药耐药性方面的研究进展作一综述。 Cancer stem cells(CSCs) are a subpopulation of tumor cells that possess self-renewal to regenerate themselves and tumor initiation capacity. CSCs possess special intrinsic mechanisms of resistance to chemotherapeutic drugs, leading to cancer recurrence and treatment failure. MicroRNAs (miRNAs) are short endogenous non-coding single-stranded RNAs that consist of 21 to 25 nucleotides. They play important roles in several cellular processes of CSCs by regulating the expression of related target genes, such as proliferation, apoptosis, and epithelial-mesenchymal transition (EMT), leading to primary CSCs drug resistance. The progress of miRNAs regulation in CSCs drug resistance was reviewed.
作者机构：
[Zhou, Fangliang; Zhang, Bo; Wei, Zheng; Zhang, Jian; Zhou, Chang; Xiang, Shuanglin; Wang, Fangmei; Hu, Xiang; Yang, Zijian; Wang, Guangwei; Ding, Xiaofeng; Zhou, Jianlin] Hunan Normal Univ, Key Lab Prot Chem & Dev Biol, State Educ Minist China, Coll Life Sci, Changsha 410081, Hunan, Peoples R China.;[Zhou, Fangliang; Zhang, Bo] Hunan Univ Chinese Med, Coll Basic Med Sci, Changsha, Hunan, Peoples R China.;[Yang, Junmei; Wang, Guangwei] Hunan Normal Univ, Sch Med, Changsha 410081, Hunan, Peoples R China.;[Xiang, Shuanglin] Hunan Normal Univ, Key Lab Prot Chem & Dev Biol, State Educ Minist China, Coll Life Sci, Lushan Rd 14, Changsha 410081, Hunan, Peoples R China.
通讯机构：
[Xiang, Shuanglin] H;Hunan Normal Univ, Key Lab Prot Chem & Dev Biol, State Educ Minist China, Coll Life Sci, Lushan Rd 14, Changsha 410081, Hunan, Peoples R China.
关键词：
EGF receptor substrate 8;glioma;cellular growth;lentiviral RNAi system;extracellular signal-regulated protein kinase;phosphorylated serine-threonine protein kinase Akt;beta-catenin
摘要：
Eps8 was initially identified as a substrate of the epidermal growth factor receptor. Overexpression of Eps8 leads to increased mitogenic signaling and malignant transformation. However, little is known concerning the importance of Eps8 in human gliomas. In this study, we found that Eps8 was overexpressed in 56.6% of human gliomas (WHO grades III and IV) compared with adjacent normal brain tissues by immunohistochemical analysis. The U251 human glioma cell line stably expressing Eps8 was established by G418 screening, and the ectopic expression of Eps8 enhanced U251 glioma cell growth and survival by cell survival, MTT and liquid colony formation assays. By contrast, the lentiviral expression of Eps8 siRNA in SHG-44 cells resulted in a significant reduction in cellular growth and proliferation. Furthermore, Eps8 modulated the levels of phosphorylated extracellular signal-regulated protein kinase (ERK), phosphorylated serine-threonine protein kinase Akt and β-catenin expression in glioma cell lines and tissues. These results suggest that Eps8 is overexpressed in human gliomas, and affects glioma cell growth possibly by regulating ERK and Akt/β-catenin signaling. Therefore, Eps8 may represent a novel potential target in human glioma therapy.
