MicroRNA-27a-3p regulates epithelial to mesenchymal transition via targeting YAP1 in oral squamous cell carcinoma cells

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs frequently dysregulated in human malignancies. Here, we profiled isolated cells from freshly resected tumors from oral squamous cell carcinoma (OSCC) patients and OSCC cell lines using a SYBR Green-based qPCR miRNA array to identify the expression change of the miRNAs. Based on the microarray data and clincopathological factor analysis of 50 OSCC patients related to these miRNAs, miR-27a-3p was selected as a putative miRNA which might play important role in OSCC progression. By bioinformatics analysis and dual-luciferase reporter assay, we found that YAP1 (Yes-associated protein-1) was a direct target gene of miR-27a-3p. Intriguingly, increased expression of miR-27a-3p could significantly decrease the expression level of YAP1 as well as several epithelial to mesenchymal transition (EMT)-related molecules in OSCC cell lines, including Twist and Snail. Then, follow-up studies revealed that miR-27a-3p expression was able to downregulate the EMT-related molecules effectively, which might be involved in the regulation of Sox2 via the YAP1-OCT4-Sox2 signaling axis. In summary, this study found that miR-27a-3p could inhibit the YAP1 directly by post-transcriptionally silencing and potentially suppress EMT process, suggesting that miR‑27a-3p might play pivotal roles in effectively manipulating the invasion and metastasis in oral squamous cell carcinoma cells through the EMT inhibition.

RETRACTED ARTICLE: MicroRNA-27a-3p Modulates the Wnt/β-Catenin Signaling Pathway to Promote Epithelial-Mesenchymal Transition in Oral Squamous Carcinoma Stem Cells by Targeting SFRP1

“…MiRNA-27a (miR-27a) is recognized as a significant regulator in carcinogenesis, including laryngeal squamous cell carcinoma10. As a member of the miR-27 family, miR-27a-3p is able to effectively manipulate the migration and invasion of OSCC cells by down-regulating the expression of EMT-related molecules11. Interestingly, secreted frizzled-related protein 1 (SFRP1) is a prior target gene among 21 candidate targets of miR-27a as found at the transcriptional level, which is, in part, similar to frizzled proteins in that it can either activate or suppress Wnt/β-catenin signaling12.…”

Long non-coding RNA H1 promotes cell proliferation and invasion by acting as a ceRNA of miR‑138 and releasing EZH2 in oral squamous cell carcinoma

“…miRNAs are a class of endogenous small non-coding RNAs, 20-25 nucleotides in length, which can suppress gene expression by directly binding to the 3'-untranslated region (3'-UTR) of target messenger RNAs (mRNAs) to induce mRNA decay or translational repression (20). Several deregulated miRNAs have also been reported in OSCC, and are involved in OSCC cell growth, apoptosis, migration and invasion (21,22). Xu et al found that miR-138 was significantly downregulated in OSCC and the overexpression of miR-138 inhibited cell proliferation OSCC in vitro and in vivo (23).…”

MicroRNA-495 confers inhibitory effects on cancer stem cells in oral squamous cell carcinoma through the HOXC6-mediated TGF-β signaling pathway

“…1f) 4 intersected miRNAs, namely hsa-miR-377, hsa-miR-27a, hsa-miR-27b, and hsa-miR-495. Previous studies have highlighted the functional mechanisms of hsa-miR-377, hsa-miR-27a, and hsa-miR-27b in OSCC [20][21][22][23][24], but the studies on the mechanism of hsa-miR-495 in OSCC were limited.…”