LINC00638 promotes the progression of non-small cell lung cancer by regulating the miR-541-3p/IRS1/PI3K/Akt axis
Juan Zhang,
Yanhua Mou,
Hui Li,
Hui Shen,
Jun Song,
Qingfeng Li
Affiliations
Juan Zhang
Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei, China; Institute of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science Hubei University of Arts and Science, Xiangyang 441021, Hubei, China
Yanhua Mou
Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei, China; Institute of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science Hubei University of Arts and Science, Xiangyang 441021, Hubei, China
Hui Li
Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei, China; Institute of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science Hubei University of Arts and Science, Xiangyang 441021, Hubei, China
Hui Shen
Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei, China; Institute of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science Hubei University of Arts and Science, Xiangyang 441021, Hubei, China
Jun Song
Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei, China; Institute of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science Hubei University of Arts and Science, Xiangyang 441021, Hubei, China
Qingfeng Li
Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei, China; Institute of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science Hubei University of Arts and Science, Xiangyang 441021, Hubei, China; Corresponding author. Department of Oncology & Institute of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136 Jingzhou Street, Xiangyang 441021, Hubei, China.
Background: Preceding works reveal the function of long non-coding RNAs (abbreviated to lncRNAs) during non-small cell lung cancer (NSCLC) evolvement. We explored the profile and biological functions of the lncRNA LINC00638 in NSCLC. Methods: Reverse transcription-quantitative PCR examined LINC00638 level in NSCLC and corresponding non-tumor tissues, human normal lung epithelial cells BEAS-2B, and NSCLC cells (NCI–H460, HCC-827, A549, H1299, H1975, H460). The gain- and loss-of-function assay of LINC00638 ascertained its function in modulating the proliferation, apoptosis, and invasion of NSCLC cells (HCC-827 and H460). Bioinformatics analysis investigated the underlying mechanisms. Dual luciferase reporter gene and RNA immunoprecipitation (RIP) checked the interactions between LINC00638 and microRNA (miR)-541-3p, miR-541-3p and insulin receptor substrate 1 (IRS1). Results: LINC00638 was upregulated in NSCLC tissues by contrast to the profiles found in the corresponding non-tumor normal tissues, as well as in NSCLC cells vis-à-vis BEAS-2B cells. LINC00638 upregulation pertained to the poorer survival rates of NSCLC patients. Overexpressing LINC00638 augmented NSCLC cells’ proliferation, growth, migration, and invasion but inhibited their apoptosis, while down-regulating LINC00638 led to the opposite. miR-541-3p might be an underlying target of LINC00638, which targeted IRS1, inhibited NSCLC progression, and reversed the carcinogenic effects of LINC00638. Mechanistically, LINC00638/miR-541-3p regulated the IRS1/phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Repressing IRS1/2 using its inhibitor NT157 repressed LINC00638-mediated oncogenic effects. Conclusion: LINC00638 may function as an oncogene in NSCLC by modulating the miR-541-3p/IRS1/PI3K/Akt axis.
