miRNome-transcriptome analysis unveils the key regulatory pathways involved in the tumorigenesis of tongue squamous cell carcinoma

Abstract

Tongue squamous cell carcinoma (TSCC) is considered the most common malignant tumor among the oral squamous cell carcinomas with a poor prognosis. Understanding the underlying molecular mechanisms that underpin TSCC and its treatments is the focus of the research. Deregulated expression of microRNAs (miRNAs) has recently been implicated in various biological processes linked to cancer. Therefore, in this study, we attempted to investigate miRNAs and their targets expressed in TSCC, which could be involved in its oncogenesis. We performed next-generation sequencing of small RNAs and transcriptomes in H357 TSCC cell line and human oral keratinocytes as a control to find miRNAs and mRNAs that are differentially expressed (DE), which were then supplemented with additional expression datasets from databases, yielding 269 DE miRNAs and 2094 DE genes. The target prediction followed by pathway and disease function analysis revealed that the DE targets were significantly associated with the key processes and pathways, such as apoptosis, epithelial–mesenchymal transition, endocytosis and vascular endothelial growth factor signaling pathways. Furthermore, the top 12 DE targets were chosen based on their involvement in more than one cancer-related pathway, of which 6 genes are targeted by miR-128-3p. Real-time quantitative PCR validation of this miRNA and its targets in H357 and SCC9 TSCC cells confirmed their possible targeting from their reciprocal expression, with MAP2K7 being a critical target that might be involved in oncogenesis and progression of TSCC by acting as a tumor suppressor. Further research is underway to understand how miR-128-3p regulates oncogenesis in TSCC via MAP2K7 and associated pathways.

miR‐203a—A multifaceted regulator modulating cancer hallmarks and therapy response

“…31 Research shows that the expression of miRNAs is significantly altered in cancer and may act as tumor suppressors or oncogenes in different cancers by sequence-specific binding with cognate mRNA targets 3 0 -UTRs. [32][33][34] Dysregulation in the expression of miRNAs affects the critical steps in oncogenic processes like metastasis, [35][36][37] angiogenesis, 38 epithelial to mesenchymal transition (EMT), 39 autophagy, 40 chemosensitivity, 41,42 and so on, by altering the signaling pathways related to these processes in a target-dependent manner. This is also associated with overall patient survival and tumor recurrence.…”

“…Evidence shows that miRNA plays a crucial role in developing and progressing several diseases, like retinal disorders, cardiovascular diseases, neurodegenerative diseases, and cancer 31 . Research shows that the expression of miRNAs is significantly altered in cancer and may act as tumor suppressors or oncogenes in different cancers by sequence‐specific binding with cognate mRNA targets 3′‐UTRs 32–34 …”