Downregulation of MicroRNA-130a Inhibits Oral Squamous Cell Carcinoma Proliferation and Metastasis via the Hippo-YAP Pathway

Abstract

Introduction Oral squamous cell carcinoma (OSCC) means oral epithelial cell injury caused by multiple genetic mutations of the cells. Dysregulation of microRNAs (miRs) can disrupt the progression of OSCC. This study explored the mechanism of miR-130a in OSCC progression. Methods miR-130a expression in OSCC cell lines was analyzed. Functional assays were utilized to test the alterations of OSCC cell proliferation, apoptosis and epithelial–mesenchymal transition (EMT) with downregulated miR-130a, shRNA-PTEN or/and YAP inhibitor verteporfin. Then, dual-luciferase reporter gene assay was performed to clarify the targeting relation between miR-130a and PTEN. After that, Hippo-YAP pathway-related protein levels were tested. Moreover, xenograft transplantation was applied to confirm the in vitro experiments. Results Highly expressed miR-130a was observed in OSCC cell lines. Silenced miR-130a reduced OSCC proliferation, metastasis, invasion and EMT while propelled apoptosis. Furthermore, miR-130a targeted PTEN to promote the OSCC progression. Downregulation of PTEN reversed the inhibition of silencing miR-130a on proliferation and migration of SCC-4 cells. miR-130a targeted PTEN to inactivate the Hippo-YAP axis. OSCC progression was notably promoted by a combination of YAP inhibitor verteporfin and miR-130a inhibitor. Additionally, silenced miR-130a inhibited OSCC progression in vivo. Discussion Silencing miR-130a inhibited OSCC progression by targeting PTEN and activating the Hippo-YAP axis. This investigation may provide novel insight for OSCC treatment.

The clinical implications of circulating microRNAs as potential biomarkers in screening oral squamous cell carcinoma

“…For example, Lin et al reported that miR-31 played a pivotal part during the progression of OSCC through establishing a complicated network with its regulated genes and the signaling cascades such as EGF-AKT signaling axis, Hippo pathway, and Wnt signaling (57). Data from the study by Peng et al revealed that downregulation of miR-130a could inhibit OSCC proliferation and metastasis by the Hippo-YAP pathway, which may provide potential target for OSCC therapy (58). Previous studies have also demonstrated that miR-133a plays tumor suppressive role in OSCC by inhibiting the Notch signaling pathway via binding to CTBP2 (59).…”

“…Data from the study by Peng et al. revealed that downregulation of miR-130a could inhibit OSCC proliferation and metastasis by the Hippo-YAP pathway, which may provide potential target for OSCC therapy ( 58 ). Previous studies have also demonstrated that miR-133a plays tumor suppressive role in OSCC by inhibiting the Notch signaling pathway via binding to CTBP2 ( 59 ).…”

Long noncoding RNA SNHG17: a novel molecule in human cancers

“…Without timely and effective treatment, it frequently leads to deformities and death. The 5-year survival rate of OSCC is 55%, with a recurrence rate of 38% [ 38 ]. SNHG17 has been found to be significantly overexpressed both in OSCC cell lines [ 39 ] and clinical samples of OSCC patients compared to controls, and its expression levels were positively correlated with adverse pathological indicators [ 40 ].…”