The role of long intergenic non-coding RNA for kinase activation (LINK-A) as an oncogene in non-small cell lung carcinoma

Parichehr Maleki,Jamshid Raheb,Soudeh Ghafouri-Fard,Mohammad Taheri,Seyed Javad Mowla

doi:10.1038/s41598-021-82892-z

Abstract

The oncogenic role of long intergenic non-coding RNA for kinase activation (LINK-A) has been appraised in triple-negative breast cancer. However, the molecular function of LINK-A is still unclear in most cancers including lung cancer. The present study aimed to evaluate the impact of down-regulation of LINK-A in A549 and Calu-3 cell lines as cellular models of non-small cell lung carcinoma (NSCLC). We used the RNA interference system to knock down LINK-A. LINK-A expression was significantly reduced by siRNA transfection in A549 and Calu-3 cell lines. LINK-A down-regulation significantly reduced cell viability, colony-forming ability and cell migration, as measured by MTT, colony formation and invasion assays. Finally, cell cycle analysis and Annexin-V/7AAD staining indicated that apoptosis was influenced by LINK-A silencing. Taken together, LINK-A can be proposed as an oncogene in NSCLC.

Highlights

The oncogenic role of long intergenic non-coding RNA for kinase activation (LINK-A) has been appraised in triple-negative breast cancer
The findings of the present study revealed that LINK-A down-regulation could induce apoptosis and reduce cell survival and proliferation in the A549 and Calu-3 cell lines
The impact of LINK-A silencing on the expression of these crucial genes and the consequent induction of apoptosis propose the oncogenic role of LINK-A in the A549 and Calu-3 cell lines and designate LINK-A as a probable therapeutic potential in lung cancer

Summary

Introduction

The oncogenic role of long intergenic non-coding RNA for kinase activation (LINK-A) has been appraised in triple-negative breast cancer. Long noncoding RNAs (lncRNA) are RNA transcripts longer than 200 nucleotides with limited coding potential, which have received enormous attention in cancer studies in the last y ears[6,7] Dysregulation of their expressions influences cell proliferation, metastasis, and invasion of tumor c ells[8,9,10]. Long intergenic non-coding RNA for kinase activation (LINK-A) is as an oncogenic cytoplasmic non-coding RNA with approximately 1.5 kbp length This lncRNA provides a scaffold-like structure in the cytoplasm which interacts with some proteins. Considering the previously known impact of LINK-A on the hyperactivation of HIF1α in triple negative-breast cancer, the current study aimed to investigate LINK-A function in Calu-3 and A549 cell lines as representative models of NSCLC. It was further aimed to examine Angiopoietin-like protein 4 (ANGPTL4), Basic Helix-Loop-Helix Family Member E40 (BHLHE40), and vascular endothelial growth factor (VEGF) expression alterations as the ultimate targets of HIF1α by relying on the aforementioned correlation between LINK-A and the hyperactivity of HIF1α and the consequent probable downstream outcomes

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