Open AccessSilencing of ISLR inhibits tumour progression and glycolysis by inactivating the IL‑6/JAK/STAT3 pathway in non‑small cell lung cancer
Author(s) -
Peng Zhang,
Zhen Li,
Guangming Yang
Publication year - 2021
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2021.5055
Subject(s) - cancer research , biology , gene silencing , lung cancer , cell growth , carcinogenesis , small interfering rna , cell cycle , gene knockdown , epithelial–mesenchymal transition , apoptosis , cancer , transfection , cell culture , metastasis , oncology , medicine , gene , biochemistry , genetics
Lung cancer is the second most frequent cancer type in both men and women, and it is considered to be one of the major causes of cancer‑related mortality worldwide. However, few biomarkers are currently available for the diagnosis of lung cancer. The aim of the present study was to investigate the function of the immunoglobulin superfamily containing leucine‑rich repeat ( ISLR ) gene in non‑small cell lung cancer (NSCLC) cells, and to elucidate the underlying molecular mechanism of its action. The current study analysed ISLR expression in NSCLC tumour and normal tissues using The Cancer Genome Atlas cohort datasets. ISLR expression in NSCLC cell lines was determined using reverse transcription‑quantitative PCR. Cell Counting Kit‑8, soft agar colony formation, wound healing, Transwell, flow cytometry and glycolysis assays were performed to determine the effects of ISLR silencing or overexpression on cells. The expression levels of the genes involved in epithelial‑mesenchymal transition (EMT), apoptosis and glycolysis were evaluated via western blotting. Transfected cells were exposed to the pathway activator, IL‑6, to validate the regulatory pathway. ISLR was overexpressed in NSCLC tissues and cell lines. Overall, patients with high ISLR expression had lower survival rates. In addition, small interfering RNA‑ ISLR inhibited the proliferation, EMT, migration, invasion and glycolysis of NSCLC cells, and promoted their apoptosis. ISLR overexpression had the opposite effect on tumour progression and glycolysis in NSCLC cells. Gene set enrichment analysis and western blotting results indicated that the IL‑6/Janus kinase (JAK)/STAT3 pathway was enriched in ISLR ‑related NSCLC. Knockdown of ISLR inhibited IL‑6‑induced proliferation, invasion, migration and glycolysis in human NSCLC cells. In summary, ISLR silencing can inhibit tumour progression and glycolysis in NSCLC cells by activating the IL‑6/JAK/STAT3 signalling pathway, which is a potential molecular target for NSCLC diagnosis and treatment.