MicroRNA-92b promotes tumor growth and activation of NF-κB signaling via regulation of NLK in oral squamous cell carcinoma

Liu,Zhiming; Diep,Cynthia; Mao,Tiantian; Huang,Li; Merrill,Robert; Zhang,Zhouwen; Peng,Youjian

doi:10.3892/or.2015.4323

MicroRNA-92b promotes tumor growth and activation of NF-κB signaling via regulation of NLK in oral squamous cell carcinoma

Authors:
- Zhiming Liu
- Cynthia Diep
- Tiantian Mao
- Li Huang
- Robert Merrill
- Zhouwen Zhang
- Youjian Peng
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Affiliations: Stomatology Center, Renmin Hospital of Wuhan University, Wuchang, Wuhan, Hubei 430060, P.R. China, UCLA School of Dentistry, Los Angeles, CA 951668, USA
Published online on: October 2, 2015 https://doi.org/10.3892/or.2015.4323
Pages: 2961-2968

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Abstract

miR-92b has been reported to be dysregulated in many types of human cancers. However, the role of miR-92b in oral squamous cell carcinoma (OSCC) is unknown. The aim of the present study was to investigate the function and mechanism of miR-92b in human OSCC. Using quantitative reverse‑transcription PCR (qRT-PCR), we found that the miR-92b level in primary tumors (n=85) was significantly elevated compared with that in the adjacent normal tissues (p<0.001). A high level of miR-92b was significantly associated with a large tumor size (p=0.005), advanced tumor stage (p<0.001) and poorer prognosis (p=0.04). Functionally, miR-92b was shown to not only promote the proliferation of OSCC cells in MTT and colony formation and xenograft assays, but also to inhibit cell apoptosis in a flow cytometric assay. In western blotting and luciferase assay, NLK was identified as a direct and functional target of miR-92b. We also found that NLK was involved in miR-92b-induced cell proliferation, and its protein level was obviously downregulated in the miR-92b-overexpressing xenograft tumors. Finally, luciferase reporter assay and fluorescent immunostaining revealed that miR-92b activated the NF-κB signaling pathway, which may be responsible for the effects of miR-92b on cell proliferation. Taken together, our results indicate that miR-92b upregulation accelerates tumor growth and present a novel mechanism of miRNA‑mediated NF-κB activation in OSCC.

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