1. Department of Thoracic Surgery, Jingjiang People's Hospital of Jiangsu Province, Jingjiang City 214500, Jiangsu Province, China
2. Department of Gastroenterology, Jingjiang People's Hospital of Jiangsu Province, Jingjiang City 214500, Jiangsu Province, China
3. Department of Bioinformatics, Nantong University Medical School, Nantong, Jiangsu 226001, People's Republic of China
*Manhui Xia and Weibo Zhu contributed equally to this work
Background: 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.
Methods: 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.
Results: 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.
Conclusion: In summary, the results of the present study showed that LASTR promotes lung cancer progression through miR-137/TGFA/PI3K/AKT axis.
Keywords: LASTR, lncRNA, lung cancer, PI3K, miRNA