Xiao Shuai, Wang Rensheng, Wu Xiangwei, Liu Wen, Ma Shanshan
1 The First Section of Radiotherapy for Head and Neck, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University , Changsha, Hunan, China .
2 Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University , Nanning, China .
DNA Cell Biol. 2018 Feb;37(2):117-125. doi: 10.1089/dna.2017.3941.
P73 antisense RNA 1T (non-protein coding), known as TP73-AS1 or PDAM, is a long noncoding RNA (lncRNA), which may regulate apoptosis by regulation of p53-dependent antiapoptotic genes. An abnormal change of TP73-AS1 expression was noticed in cancers. The effects of TP73-AS1 in brain glioma growth and the underlying mechanism remain unclear so far. In this study, the effect of TP73-AS1 in human brain glioma cell lines and clinical tumor samples was detected so as to reveal its role and function. In this study, TP73-AS1 was specifically upregulated in brain glioma cell lines and promoted glioma cell growth through targeting miR-124. TP73-AS1 knocking down suppressed human brain glioma cell proliferation, invasion, and metastasis in vitro. The inhibitory effect of TP73-AS1 knocking down on glioma cell proliferation and invasion could partly be restored by miR-124 inhibition. In addition, miR-124-dependent inhibitor of apoptosis-stimulating protein of p53 (iASPP) regulation was required in TP73-AS1-induced brain glioma cell growth. Data from this study revealed that TP73-AS1 inhibited the brain glioma growth and metastasis as a competing endogenous RNA (ceRNA) through miR-124-dependent iASPP regulation. In conclusion, we regarded TP73-AS1 as an oncogenic lncRNA promoting brain glioma proliferation and metastasis and a potential target for human brain glioma treatment.
P73反义RNA 1T（非蛋白质编码），也称为TP73-AS1或PDAM，是一种长链非编码RNA（lncRNA），它可能通过调控p53依赖的抗凋亡基因来调节细胞凋亡。在癌症中发现了TP73-AS1表达的异常变化。迄今为止，TP73-AS1在脑胶质瘤生长中的作用及其潜在机制仍不清楚。在本研究中，检测了TP73-AS1在人脑胶质瘤细胞系和临床肿瘤样本中的作用，以揭示其作用和功能。在本研究中，TP73-AS1在脑胶质瘤细胞系中特异性上调，并通过靶向miR-124促进胶质瘤细胞生长。敲低TP73-AS1可抑制人脑胶质瘤细胞在体外的增殖、侵袭和转移。抑制miR-124可部分恢复敲低TP73-AS1对胶质瘤细胞增殖和侵袭的抑制作用。此外，TP73-AS1诱导的脑胶质瘤细胞生长需要miR-124依赖的p53凋亡刺激蛋白抑制因子（iASPP）调控。本研究数据表明，TP73-AS1作为一种竞争性内源RNA（ceRNA），通过miR-124依赖的iASPP调控抑制脑胶质瘤的生长和转移。总之，我们认为TP73-AS1是一种促进脑胶质瘤增殖和转移的致癌lncRNA，是人类脑胶质瘤治疗的潜在靶点。
