Differential Expression of Genes Regulating Store-operated Calcium Entry in Conjunction With Mitochondrial Dynamics as Potential Biomarkers for Cancer: A Single-Cell RNA Analysis

Regulation of intracellular concentration of calcium levels is crucial for cell signaling, homeostasis, and in the pathology of diseases including cancer. Agonist-induced entry of calcium ions into the non-excitable cells is mediated by store-operated calcium channels (SOCs). This pathway is activat...

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Published in:Frontiers in genetics 2022-05, Vol.13, p.866473-866473
Main Authors: Hegde, Mangala, Daimary, Uzini Devi, Jose, Sandra, Sajeev, Anjana, Chinnathambi, Arunachalam, Alharbi, Sulaiman Ali, Shakibaei, Mehdi, Kunnumakkara, Ajaikumar B.
Format: Article
Language:English
Subjects:
CPTAC database
gene expression omnibus
Genetics
head and neck cancer
mitochondrial dynamics
store-operated calcium channels
TCGA database
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Summary:Regulation of intracellular concentration of calcium levels is crucial for cell signaling, homeostasis, and in the pathology of diseases including cancer. Agonist-induced entry of calcium ions into the non-excitable cells is mediated by store-operated calcium channels (SOCs). This pathway is activated by the release of calcium ions from the endoplasmic reticulum and further regulated by the calcium uptake through mitochondria leading to calcium-dependent inactivation of calcium-release activated calcium channels (CARC). SOCs including stromal interaction molecules (STIM) and ORAI proteins have been implicated in tumor growth, progression, and metastasis. In the present study, we analyzed the mRNA and protein expression of genes mediating SOCs—STIM1, STIM2, ORAI1, ORAI2, ORAI3, TRPC1, TRPC3, TRPC4, TRPC5, TRPC6, TRPC7, TRPV1, TRPV2, TRPM1, and TRPM7 in head and neck squamous cell cancer (HNSC) patients using TCGA and CPTAC analysis. Further, our in silico analysis showed a significant correlation between the expression of SOCs and genes involved in the mitochondrial dynamics (MDGs) both at mRNA and protein levels. Protein-protein docking results showed lower binding energy for SOCs with MDGs. Subsequently, we validated these results using gene expression and single-cell RNA sequencing datasets retrieved from Gene Expression Omnibus (GEO). Single-cell gene expression analysis of HNSC tumor tissues revealed that SOCs expression is remarkably associated with the MDGs expression in both cancer and fibroblast cells.
ISSN:1664-8021
1664-8021
DOI:10.3389/fgene.2022.866473