miR-100 Inhibits Cell Growth and Proliferation by Targeting HOXA1 in Nasopharyngeal Carcinoma

miR-100通过靶向HOXA1抑制鼻咽癌细胞的生长和增殖

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Abstract

BACKGROUND: Increasing evidence indicates that the dysregulation of miRNAs plays a vital role in tumorigenesis and progression of nasopharyngeal carcinoma (NPC). Thus, it is necessary to further investigate the function and mechanism of miRNAs in NPC. METHODS: miR-100 expression was analyzed using publicly available databases and then tested using quantitative RT-PCR in NPC tissues and cell lines. MTT and colony formation assays and xenograft tumor model were used to test the NPC cell growth and proliferation abilities while modulating miR-100 expression. The target of miR-100 was predicted with TargetScan and validated with luciferase reporter assay, quantitative RT-PCR, and Western blot. RESULTS: The expression of miR-100 was significantly reduced in NPC tissues and cell lines. Overexpression of miR-100 obviously suppressed NPC cell growth and proliferation, whereas silencing miR-100 promoted NPC cell growth and proliferation in vitro. HOXA1 (homeobox A1) was validated as a direct target of miR-100, and restoring HOXA1 expression could reverse the inhibitive effect of miR-100 on NPC cell growth and proliferation. The mRNA and protein expression of HOXA1 was increased in NPC cell lines. Furthermore, ectopic expression of miR-100 inhibited xenograft tumor growth in vivo. CONCLUSION: Taken together, our findings suggest that miR-100 could suppress NPC growth and proliferation through targeting HOXA1, providing a novel target for the miRNA-mediated therapy for patients with NPC in the future.

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