Unravelling the Role of miR-20b-5p, CCNB1, HMGA2 and E2F7 in Development and Progression of Non-Small Cell Lung Cancer (NSCLC).

Shweta Arora,Arshad Husain Rahmani,Prithvi Singh,Ravins Dohare,Mansoor Ali Syed,Saleh A Almatroodi

doi:10.3390/biology9080201

Shweta Arora, Arshad Husain Rahmani + Show 4 more

Open Access

https://doi.org/10.3390/biology9080201

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Abstract

Lung cancer is a prime cause of worldwide cancer deaths, with non-small cell lung cancer (NSCLC) as a frequent subtype. Surgical resection, chemotherapy are the currently used treatment methods. Delayed detection, poor prognosis, tumor heterogeneity, and chemoresistance make them relatively ineffective. Genomic medicine is a budding aspect of cancer therapeutics, where miRNAs are impressively involved. miRNAs are short ncRNAs that bind to 3′UTR of target mRNA, causing its degradation or translational repression to regulate gene expression. This study aims to identify important miRNA-mRNA-TF interactions in NSCLC using bioinformatics analysis. GEO datasets containing mRNA expression data of NSCLC were used to determine differentially expressed genes (DEGs), and identification of hub genes-BIRC5, CCNB1, KIF11, KIF20A, and KIF4A (all functionally enriched in cell cycle). The FFL network involved, comprised of miR-20b-5p, CCNB1, HMGA2, and E2F7. KM survival analysis determines that these components may be effective prognostic biomarkers and would be a new contemplation in NSCLC therapeutics as they target cell cycle and immunosurveillance mechanisms via HMGA2 and E2F7. They provide survival advantage and evasion of host immune response (via downregulation of cytokines-IL6, IL1R1 and upregulation of chemokines-CXCL13, CXCL14) to NSCLC. The study has provided innovative targets, but further validation is needed to confirm the proposed mechanism.

Highlights

Lung cancer is the trivial cause of cancer-associated worldwide deaths with a flat overall 5-year survival rate of less than 15%
non-small cell lung cancer (NSCLC)-Associated Meta-differentially expressed genes (DEGs) Identification mRNA datasets with accession numbers GSE118370 and GSE18842 were chosen from Gene Expression Omnibus (GEO) based on the search criteria specified in materials and methods section
A total of 603 meta-DEGs were identified based on the Benjamini and Hochberg (BH)- p-value and log2 fold change (log2 FC) threshold criterion

Summary

Introduction

Lung cancer is the trivial cause of cancer-associated worldwide deaths with a flat overall 5-year survival rate of less than 15%. It is patho-physiologically divided into two subgroups: highly aggressive, but less frequent (~15%) small cell lung cancer (SCLC) and less aggressive but highly intermittent (~85%) non-small cell lung cancer (NSCLC). NSCLC is further histologically subdivided into three subtypes—adenocarcinoma (40%), squamous cell carcinoma (25%), and large cell carcinoma (10%). Lung cancer usually commences with oncogene activation or tumor suppressor gene inactivation [1]. Despite developments of innovative therapies, the survival rate for NSCLC patients still remains low. Histological subtype tumor heterogeneities, and restrained understanding

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