Qian Ke, Liu Gao, Tang Zhonghua, Hu Yibo, Fang Yu, Chen Zonglin, Xu Xundi
Department of Breast and Thyroid Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Division of Hepatobiliary Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Arch Biochem Biophys. 2017 Feb 1;615:1-9. doi: 10.1016/j.abb.2016.12.011. Epub 2016 Dec 26.
Nuclear enriched abundant transcript 1 (NEAT1), an important cancer-associated long non-coding RNA (lncRNA), contributes to the development and progression of several cancers. An increased expression of NEAT1 was observed in cancers including bladder cancer, lung cancer and breast cancer (BC). However, the exact effect of NEAT1 in BC progression and the underlying molecular mechanisms are still unknown up to now. Here, we investigated the detailed role of NEAT1 in human BC cell lines and clinical tumor samples in order to validate the function of this molecule. In our research, lncRNA-NEAT1 was specifically upregulated in BC cell lines and promoted BC cell growth through targeting miR-101. Knockdown of NEAT1 inhibited the proliferation and DNA synthesis of human BC cell in vitro. In addition, the regulation of EZH2 by miR-101 was required in NEAT1 induced BC cell growth. These findings indicated that NEAT1 might suppress the tumor growth via miR-101 dependent EZH2 regulation. Taken together, our data indicated that NEAT1 might be an oncogenic lncRNA that promoted proliferation of BC and could be regarded as a therapeutic target in human BC.
核富集丰富转录本1(NEAT1)是一种重要的癌症相关长链非编码RNA(lncRNA),它在多种癌症的发生和发展过程中发挥作用。在包括膀胱癌、肺癌和乳腺癌(BC)在内的多种癌症中均观察到NEAT1表达上调。然而,截至目前,NEAT1在BC进展中的具体作用及潜在分子机制仍不清楚。在此,我们研究了NEAT1在人BC细胞系和临床肿瘤样本中的详细作用,以验证该分子的功能。在我们的研究中,lncRNA-NEAT1在BC细胞系中特异性上调,并通过靶向miR-101促进BC细胞生长。敲低NEAT1可抑制人BC细胞在体外的增殖和DNA合成。此外,NEAT1诱导的BC细胞生长需要miR-101对EZH2的调控。这些发现表明,NEAT1可能通过miR-101依赖的EZH2调控抑制肿瘤生长。综上所述,我们的数据表明,NEAT1可能是一种致癌lncRNA,可促进BC增殖,有望成为人BC的治疗靶点。