Xia Manhui, Zhu Weibo, Tao Chunmu, Lu Yuntian, Gao Feng
Department of Thoracic Surgery, Jingjiang People's Hospital of Jiangsu Province, Jingjiang City 214500, Jiangsu Province, China.
Department of Gastroenterology, Jingjiang People's Hospital of Jiangsu Province, Jingjiang City 214500, Jiangsu Province, China.
J Cancer. 2022 Jan 6;13(4):1086-1096. doi: 10.7150/jca.66067. eCollection 2022.
Long noncoding RNAs (LncRNAs) are widely involved in the physiological and pathophysiological processes of cells. This study sought to identify novel lncRNAs that play key roles in progression of lung cancer. Cells were purchased from the Cell Bank of Type Culture Collection of the Chinese Academy of Sciences. Public lung cancer data were retrieved from The Cancer Genome Atlas database. Statistical analyses were performed using SPSS, R and GraphPad Prism 8 software. Bioinformatic analysis showed that the lncRNA, LASTR (ENSG00000242147) was significantly upregulated in lung cancer tissues (LUAD and LUSC) compared with the expression level in adjacent normal tissue. Kaplan-Meier survival analysis showed that patients with higher LASTR expression level had a shorter overall survival and worse clinical features relative to patients with low LASTR expression levels. qRT-PCR results showed that LASTR was highly expressed in lung cancer cell lines relative to the expression level in normal lung epithelial cell line. Cell phenotype experiments indicated that knockdown of LASTR significantly inhibited proliferation and metastatic ability of lung cancer cells. Analysis of the downstream mechanism of LASTR demonstrated that LASTR exerts the oncogene effect through the miR-137/TGFA axis. GSEA results indicated that LASTR exhibits its activity by activating the PI3K/AKT signaling pathway, which was validated by western blotting assay. In summary, the results of the present study showed that LASTR promotes lung cancer progression through miR-137/TGFA/PI3K/AKT axis.
长链非编码RNA（LncRNAs）广泛参与细胞的生理和病理生理过程。本研究旨在鉴定在肺癌进展中起关键作用的新型lncRNAs。细胞购自中国科学院典型培养物保藏委员会细胞库。从癌症基因组图谱数据库检索公开的肺癌数据。使用SPSS、R和GraphPad Prism 8软件进行统计分析。生物信息学分析表明，与邻近正常组织中的表达水平相比，lncRNA LASTR（ENSG00000242147）在肺癌组织（肺腺癌和肺鳞癌）中显著上调。Kaplan-Meier生存分析表明，与LASTR表达水平低的患者相比，LASTR表达水平高的患者总生存期较短，临床特征较差。qRT-PCR结果表明，相对于正常肺上皮细胞系中的表达水平，LASTR在肺癌细胞系中高表达。细胞表型实验表明，敲低LASTR可显著抑制肺癌细胞的增殖和转移能力。对LASTR下游机制的分析表明，LASTR通过miR-137/TGFA轴发挥癌基因作用。基因集富集分析（GSEA）结果表明，LASTR通过激活PI3K/AKT信号通路发挥其活性，蛋白质免疫印迹分析验证了这一点。总之，本研究结果表明，LASTR通过miR-137/TGFA/PI3K/AKT轴促进肺癌进展。
