MicroRNA-92b promotes tumor growth and activation of NF-κB  signaling via regulation of NLK in oral squamous cell carcinoma.
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.
Zhiming
Z
Liu
Cynthia
C
Diep
Tiantian
T
Mao
Li
L
Huang
Robert
R
Merrill
Zhouwen
Z
Zhang
Youjian
Y
Peng
D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
D020413:3' Untranslated Regions; D047908:Intracellular Signaling Peptides and Proteins; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; C470551:NLK protein, human; D017346:Protein Serine-Threonine Kinases