MiR-98 inhibits malignant progression via targeting MTDH in squamous cell carcinoma of the head and neck

Purpose: MicroRNAs function through regulating specific target mRNA expression and then participate in the development and progression of diverse human cancers. MiR-98 shows aberrant expression and dysfunction in tumors. However, its clinical significance and exact role in squamous cell carcinoma of the head and neck (SCCHN) remain elusive.

Methods: MiR-98 expression was examined by qRT-PCR and correlated with clinicopathological variables and prognosis in SCCHN patients. Effects of miR-98 on epithelial-mesenchymal transition (EMT) and the malignant phenotypes of SCCHN were studied. Finally, the role of target gene metadherin (MTDH) in miR-98 mediated effects were assayed.

Results: Our results demonstrated that miR-98, as an endogenous inhibitor of MTDH via directly binding to its 3'-untranslated region (UTR) region, decreased significantly in SCCHN tissues. Decreased miR-98 expression was negatively correlated with T classification, clinical stage, lymph node metastasis and a shorter survival status in SCCHN patients. Loss-of-function and gain-of-function analyses confirmed that miR-98 inhibited cell proliferation, migration and invasion of SCCHN cells in vitro. Moreover, miR-98 repression led to increased MTDH expression and induced EMT alteration. Importantly, ectopic expression of MTDH partially reversed the effects caused by miR-98 overexpression.

Conclusions: Our study identifies that miR-98 serves as a suppressor in SCCHN progression via targeting oncogene MTDH.