Abstract
Background: The relationship between miR-29b-1-5p and c-Met proto-oncogene in oral squamous cell carcinoma (OSCC) remains to be investigated. This study aimed to reveal the role of miR-29b-1-5p in the pathogenesis of OSCC using molecular and biological analyses. Methods: We investigated the expression of miR-29b-1-5p, c-Met, and markers of the epithelial-mesenchymal transition (EMT) in the tissues of 49 patients with OSCC and in human OSCC cells with different tumorigenicity. Further, we determined the effects of miR-29b-1-5p on the phenotypes of OSCC cell lines. Results: The expression levels of miR-29b-1-5p in most patients with OSCC were higher than those of the normal oral epithelium. In OSCC, upregulation of miR-29b-1-5p significantly correlated with histological grade, the EMT, and the immunohistochemical grade, indicated by c-Met expression. The prognosis was poor for patients with miR-29b-1-5p expression and coexpression of miR-29b-1-5p and c-Met. In OSCC cells exhibiting the EMT phenotype, knockdown of miR-29b-1-5p suppressed the EMT, which was recovered by enforced expression of c-Met. Further, the mRNA encoding cadherin 1 (CDH1) was a direct target of miR-29b-1-5p. Conclusions: Our results suggest that miR-29b-1-5p acts as an oncogenic miRNA that synergizes with c-Met to induce the EMT of OSCC cells.
Highlights
Cancer of the head and neck, including oral squamous cell carcinoma (OSCC), is the sixth most common malignant tumor worldwide, with approximately 529,500 patients and 292,300 deaths annually, which represent approximately 3.8% of all cancer cases and 3.6% of cancer-related deaths [1,2]
Representative data for c-Met expression and epithelial-mesenchymal transition (EMT) markers show that 55.1% (27/49) and 38.8% (19/49) of OSCC samples were positive for c-Met overexpression and EMT markers, respectively (Figure 1b,c)
We prevent compelling evidence that supports the conclusion that miR-29b-1-5p acts as an oncomiR and that miR-29b-1-5p and MET cooperate to induce OSCC cells to undergo the EMT
Summary
Cancer of the head and neck, including oral squamous cell carcinoma (OSCC), is the sixth most common malignant tumor worldwide, with approximately 529,500 patients and 292,300 deaths annually, which represent approximately 3.8% of all cancer cases and 3.6% of cancer-related deaths [1,2]. MicroRNAs (miRNAs) (approximately 18–25 nucleotides) are noncoding single-stranded RNAs that inhibit gene expression by binding to the 3 -untranslated regions (UTR) of target mRNAs [5]. A single strand of mature miRNA is incorporated along with argonaute RISC catalytic component 2 (AGO2) into an RNA-induced silencing complex (RISC) that inhibits the expression of a target mRNA [5,6]. The relationship between miR-29b-1-5p and c-Met proto-oncogene in oral squamous cell carcinoma (OSCC) remains to be investigated. Methods: We investigated the expression of miR-29b-1-5p, c-Met, and markers of the epithelial-mesenchymal transition (EMT) in the tissues of 49 patients with OSCC and in human OSCC cells with different tumorigenicity. Conclusions: Our results suggest that miR-29b-1-5p acts as an oncogenic miRNA that synergizes with c-Met to induce the EMT of OSCC cells
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