Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.
J Cell Biochem. 2018 Jan;119(1):680-690. doi: 10.1002/jcb.26231. Epub 2017 Oct 5.
P73 antisense RNA 1T (TP73-AS1 or PDAM) is a long non-coding RNA, which can regulate apoptosis through regulation of p53 signaling-related anti-apoptotic genes. An abnormal change of TP73-AS1 expression was noticed in cancers. The effects of TP73-AS1 in breast cancer (BC) growth and the underlying mechanism remain unclear so far. In the present study, the effect of TP73-AS1 in BC cell lines and clinical tumor samples was detected so as to reveal its role and function. In the present study, TP73-AS1 was specifically upregulated in BC tissues and BC cell lines and was correlated to a poorer prognosis in patients with BC. TP73-AS1 knocking down suppressed human BC cell proliferation in vitro through regulation of TFAM. In our previous study, we demonstrated that miR-200a inhibits BC cell proliferation through targeting TFAM; here we revealed that TP73-AS1 could regulate miR-200a through direct targeting. Moreover, TP73-AS1 might compete with TFAM for miR-200a binding thus to promote TFAM expression. Data from the present study revealed that TP73-AS1 promoted BC cell proliferation through acting as a competing endogenous RNA (ceRNA) by sponging miR-200a. In conclusion, we regarded TP73-AS1 as an oncogenic lncRNA promoting BC cell proliferation and a potential target for human BC treatment.
P73 反义 RNA 1T（TP73-AS1 或 PDAM）是一种长链非编码 RNA，可以通过调节 p53 信号相关的抗凋亡基因来调节细胞凋亡。在癌症中注意到 TP73-AS1 表达的异常变化。TP73-AS1 在乳腺癌（BC）生长中的作用及其潜在机制迄今尚不清楚。在本研究中，检测了 TP73-AS1 在 BC 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 BC 组织和 BC 细胞系中特异性上调，并与 BC 患者的预后不良相关。TP73-AS1 敲低通过调节 TFAM 抑制体外人 BC 细胞增殖。在我们之前的研究中，我们证明了 miR-200a 通过靶向 TFAM 抑制 BC 细胞增殖；在这里，我们揭示了 TP73-AS1 可以通过直接靶向调节 miR-200a。此外，TP73-AS1 可能与 TFAM 竞争 miR-200a 结合，从而促进 TFAM 表达。本研究的数据表明，TP73-AS1 通过作为竞争性内源性 RNA（ceRNA）来吸收 miR-200a 促进 BC 细胞增殖。总之，我们认为 TP73-AS1 是一种致癌的 lncRNA，可促进 BC 细胞增殖，是人类 BC 治疗的潜在靶点。
