title: Downregulation of cytochrome c oxidase subunit 7A1 expression is important in enhancing cell proliferation in adenocarcinoma cells.
abstract: Mitochondrial Dysfunction has been implicated in multiple human diseases, including cancer. Among all cancer, lung cancer is the most common type of cancer worldwide with low survival rates. Mammals possess multiple subunits of the mitochondrial enzyme Cytochrome C oxidase (COX). The COX subunits are expressed in a tissue specific manner and have been implicated in cancer cell metabolism although their molecular and regulatory mechanisms are not clearly understood. In this study, we aimed at identifying novel gene signatures in lung cancer. We performed extensive analysis of seven different Gene Expression Omnibus (GEO) datasets pertaining to different stages of lung adenocarcinoma and identified that multiple subunits of COX genes are differentially expressed in these patients. Amongst all COX genes, the expression of COX7A1 gene was observed to be highly down regulated in these patients. In order to validate the GEO datasets, we looked at the expression of multiple COX genes using quantitative real time PCR (qPCR) using human lung adenocarcinoma cell line A549. Our results confirmed that COX 7A1 gene expression was indeed highly reduced in these cells. Overexpression of COX7A1 in human lung cancer cells led to inhibition of cell proliferation and increase in cell death via apoptosis. These results indicated that low level of COX7A1 gene expression is essential to regulate cell viability and inhibit cell death in lung adenocarcinoma. Our study has identified COX7A1 as a novel gene that might play a crucial role in the etiology of lung adenocarcinoma and can serve as a biomarker for lung cancer disease progression.
authors.affiliation: Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi, 110021, India.
authors.forename: Nawneet
authors.initials: N
authors.lastname: Mishra
authors.affiliation: Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi, 110021, India.
authors.forename: Uddhav
authors.initials: U
authors.lastname: Timilsina
authors.affiliation: Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi, 110021, India.
authors.forename: Dibya
authors.initials: D
authors.lastname: Ghimire
authors.affiliation: Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi, 110021, India.
authors.forename: Ravi C
authors.initials: RC
authors.lastname: Dubey
authors.affiliation: Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi, 110021, India. Electronic address: rgaur@sau.ac.in.
authors.forename: Ritu
authors.initials: R
authors.lastname: Gaur
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis; D001562:Benzimidazoles / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D018450:Disease Progression; D015536:Down-Regulation; D003576:Electron Transport Complex IV / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000473:pathology; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress
chemical_list: D001562:Benzimidazoles; D014408:Biomarkers, Tumor; C513901:COX7A1 protein, human; D003576:Electron Transport Complex IV; C017807:bisbenzimide ethoxide trihydrochloride
keywords: Adenocarcinoma; Cell death; Cytochrome c oxidase