Transcriptome profiling-based evidences reiterate the intrinsic role of MAPKAPK2 in facilitating molecular crosstalk during HNSCC pathogenesis

Abstract

BackgroundTranscriptome profiling has been pivotal in better comprehending the convoluted biology of tumors including head and neck squamous cell carcinoma (HNSCC). Recently, growing evidence has implicated the role of mitogen-activated protein kinase-activated protein kinase-2 (MAPKAPK2 or MK2) in many human diseases including tumors. MK2 has been recently reported as a critical regulator of HNSCC that functions via modulating the transcript turnover of crucial genes involved in its pathogenesis. Comprehensive MK2-centric transcriptomic analyses could help the scientific community to delve deeper into MK2-pathway driven mechanisms of tumor progression, but such studies have not yet been reported. Consequently, to delineate the biological relevance of MK2 and its intricate crosstalk in the tumor milieu, an extensive transcriptome analysis of HNSCC was conceptualized and effectuated with MK2 at the nexus. MethodsIn the current study, comprehensive next-generation sequencing-based transcriptome profiling was accomplished to ascertain global patterns of mRNA expression profiles in both in vitro and in vivo models of the HNSCC microenvironment. The findings of the RNA-sequencing analysis were cross-validated via robust validation using nCounter gene expression assays, immunohistochemistry, and real-time quantitative polymerase chain reaction (RT-qPCR). ResultsTranscriptomic characterization followed by annotation and differential gene expression analyses identified certain MK2-regulated candidate genes constitutively involved in regulating HNSCC pathogenesis, and the biological significance of these genes was established by pathway enrichment analysis. Additionally, advanced gene expression assays through the nCounter system in conjunction with immunohistochemical analysis validated the transcriptome profiling outcomes quite robustly. Furthermore, the results obtained from immunohistochemistry and transcript stability analysis indicated the crucial role of MK2 in the modulation of the expression pattern of these genes in HNSCC tumors and cells. ConclusionsConclusively, the findings have paved the way toward the identification of new effective tumor markers and potential molecular targets for HNSCC management. The results have accentuated the importance of certain differentially expressed MK2-regulated genes that are constitutively involved in HNSCC pathogenesis to potentially serve as putative candidates for future endeavors pertaining to diagnosis and therapeutic interventions for HNSCC.