LINC00638 promotes the progression of non-small cell lung cancer by regulating the miR-541-3p/IRS1/PI3K/Akt axis

  • Heliyon. 2023 Jun 15;9(6):e16999. doi: 10.1016/j.heliyon.2023.e16999.
Juan Zhang  1  2 ,  Yanhua Mou  1  2 ,  Hui Li  1  2 ,  Hui Shen  1  2 ,  Jun Song  1  2 ,  Qingfeng Li  1  2
Affiliations
  • 1. Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei, China.
  • 2. 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.
PMID: 37408901 DOI: 10.1016/j.heliyon.2023.e16999
Abstract

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.

Keywords
Insulin receptor substrate 1; LINC00638; Non-small cell lung cancer; Progression; miR-541-3p.
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