Silencing of <em>ISLR</em> inhibits tumour progression and glycolysis by inactivating the IL‑6/JAK/STAT3 pathway in non‑small cell lung cancer

Zhang,Peng; Li,Zhen; Yang,Guangming

doi:10.3892/ijmm.2021.5055

Silencing of ISLR inhibits tumour progression and glycolysis by inactivating the IL‑6/JAK/STAT3 pathway in non‑small cell lung cancer

Authors:
- Peng Zhang
- Zhen Li
- Guangming Yang
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Affiliations: Department of Pulmonary and Critical Care Medicine, Shandong Second Provincial General Hospital, Ji'nan, Shandong 250022, P.R. China, Department of Tumor Radiotherapy, Shandong Second Provincial General Hospital, Ji'nan, Shandong 250022, P.R. China
Published online on: October 26, 2021 https://doi.org/10.3892/ijmm.2021.5055
Article Number: 222
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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