Department of Thoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, China.
Department of Thoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, China.
Biochem Biophys Res Commun. 2019 Aug 20;516(2):486-493. doi: 10.1016/j.bbrc.2019.06.088. Epub 2019 Jun 21.
Long noncoding RNAs (lncRNAs), a large group of RNAs with limited or no protein-coding capacity, have been demonstrated to play critical roles in human malignancy. The aim of this study is to examine the expression and function TMPO antisense transcript 1 (TMPO-AS1) in non-small cell lung cancer (NSCLC). Here, we found that the expression of both TMPO-AS1 and TMPO mRNA levels were overexpressed in NSCLC cells lines and tissues. A significant positive correlation was observed between TMPO-AS1 and TMPO mRNA levels. The upregulation of TMPO-AS1, TMPO mRNA and protein levels were associated with tumor progression of NSCLC. More importantly, through antisense pairing with TMPO mRNA, TMPO-AS1 regulates TMPO mRNA stability. Knockdown of TMPO-AS1 decreased the mRNA and protein levels of TMPO in NSCLC cells. An overlapping (OL) region was found between TMPO-AS1 and TMPO exon 1 and overexpression of TMPO-AS1-OL elevated the mRNA and protein levels of TMPO. Functionally, the downregulation of TMPO-AS1 significantly inhibited cells proliferation, colony formation, migration and invasiveness in vitro, and tumor growth in vivo. In contrast, overexpression of TMPO could promote the aggressive behaviors of NSCLC cells in vitro. Our findings indicate that TMPO-AS1 contributes to lung carcinogenesis, which may be partially through upregulation TMPO.
长链非编码 RNA（lncRNA）是一组具有有限或无蛋白编码能力的 RNA，已被证明在人类恶性肿瘤中发挥关键作用。本研究旨在研究 TMPO 反义转录本 1（TMPO-AS1）在非小细胞肺癌（NSCLC）中的表达和功能。在这里，我们发现 TMPO-AS1 和 TMPO mRNA 水平在 NSCLC 细胞系和组织中均过度表达。TMPO-AS1 和 TMPO mRNA 水平之间存在显著正相关。TMPO-AS1、TMPO mRNA 和蛋白水平的上调与 NSCLC 的肿瘤进展相关。更重要的是，通过与 TMPO mRNA 反义配对，TMPO-AS1 调节 TMPO mRNA 的稳定性。TMPO-AS1 的敲低降低了 NSCLC 细胞中 TMPO 的 mRNA 和蛋白水平。在 TMPO-AS1 和 TMPO 外显子 1 之间发现了一个重叠（OL）区域，TMPO-AS1-OL 的过表达提高了 TMPO 的 mRNA 和蛋白水平。功能上，TMPO-AS1 的下调显著抑制了 NSCLC 细胞在体外的增殖、集落形成、迁移和侵袭能力，以及体内的肿瘤生长。相比之下，TMPO 的过表达可促进 NSCLC 细胞在体外的侵袭行为。我们的研究结果表明，TMPO-AS1 促进了肺癌的发生，这可能部分是通过上调 TMPO 实现的。
