Non-coding microRNAs (miRNAs) have been proposed to play diverse roles in cancer biology, including epithelial-mesenchymal transition (EMT) crucial for cancer progression. Previous comparative studies revealed distinct expression profiles of miRNAs relevant to tumorigenesis and progression of oral cancer. With putative targets of these miRNAs mostly validated , it remains unclear whether similar miRNA-target relationships exist . In this study, we employed a hybrid approach, utilizing both and human oral cancer cells, to validate projected miRNA-target relationships relevant to EMT. Notably, overexpression of resulted in significant tissue growth in larval wing discs. The RT-PCR analysis successfully validated a subset of its putative targets, including . Subsequent experiments performed in oral cancer cells confirmed conserved targeting of human by . Furthermore, the elevated level of miR-133 and its targeting of was positively correlated with enhanced migrative ability of oral cancer cells treated with LPS, along with the molecular signature of a facilitated EMT process induced by LPS and TGF-β. The analysis on the RNAseq data also revealed a negative correlation between the expression level of and the survival of oral cancer patients. Taken together, our mammal-to--to-mammal approach successfully validates targeting of by miR-133 both and , underlying the promoted EMT phenotypes and potentially influencing the prognosis of oral cancer patients. This hybrid approach will further aid to widen our scope in investigation of intractable human malignancies, including oral cancer.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317528PMC
http://dx.doi.org/10.7150/jca.56138DOI Listing

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