MiR-135a-5p represses proliferation of HNSCC by targeting HOXA10
MiR-135a-5p represses proliferation of HNSCC by targeting HOXA10
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DOI：
10.1080/15384047.2018.1450112
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发表时间：
2018-11-02
影响因子：
3.6
通讯作者：
Lu, Yufei
中科院分区：
文献类型：
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作者：
Guo, Lei-ming;Ding, Gao-feng;Lu, Yufei
目的：本研究旨在探讨miR-135 a-5 p在头颈部鳞状细胞癌（HNSCC）细胞中的作用及其对细胞活力的影响。此外，我们旨在比较miR-135 a-5 p和miR-494在HNSCC中的作用，发现其抑制口腔癌中HOXA 10的表达。方法：采用绿色荧光蛋白报告基因分析和qRT-PCR方法检测miR-135 a-5 p与HOXA 10的相关性。采用蛋白质印迹法检测HNSCC细胞系（CAL-27、FaDu和NEC）中HOXA 10的表达水平。在用miR-135 a-5 p模拟物和miR-494模拟物转染后，通过蛋白质印迹检测FaDu细胞和CAL-27细胞中HOXA 10的表达水平。分别采用集落形成实验和流式细胞术检测转染HOXA 10质粒和HOXA 10-KO质粒后HNSCC细胞的增殖和凋亡情况。进行体外肿瘤异种移植实验以分析miR-135 a-5 p对巴拉/c小鼠中HOXA 10的抑制作用。结果：HOXA 10在HNSCC细胞中高表达，而miR-135 a-5 p在HNSCC细胞中低表达。因此，HOXA 10的低表达延长了无病生存时间和总生存时间。miR-135 a-5 p过表达可通过直接靶向HOXA 10 3 ' UTR抑制HOXA 10的表达，且抑制效果优于miR-494。HOXA 10抑制抑制HNSCC细胞增殖并增强细胞凋亡。体内实验表明，miR-135 a-5 p可通过下调HOXA 10表达来减缓小鼠肿瘤细胞的生长。结论：miR-135 a-5 p可通过直接靶向HOXA 10抑制HNSCC细胞增殖并促进细胞凋亡，提示miR-135 a-5 p在HNSCC治疗中具有重要意义。
Objectives: This research aimed to explore the role of miR-135a-5p in head and neck squamous cell carcinoma (HNSCC) cells and its influence on cell viability. Moreover, we aimed to compare effects of miR-135a-5p and miR-494 in HNSCC, which was found to repress HOXA10 expression in oral cancer. Methods: The association between miR-135a-5p and HOXA10 was confirmed by green fluorescence protein reporter assay and qRT-PCR. The expression levels of HOXA10 in HNSCC cell lines (CAL-27, FaDu and NEC) were examined using western blot. The expression levels of HOXA10 in FaDu cells and CAL-27 cells were examined by western blot after transfection with miR-135a-5p mimics and miR-494 mimics. Colony formation assay and flow cytometry assay were respectively utilized to detect the proliferation and apoptosis of HNSCC cells after transfection with HOXA10 plasmids and HOXA10-KO plasmids. In vitro tumor xenograft experiments were performed to analyze the inhibitive effect of miR-135a-5p on HOXA10 in BALA/c mice. Results: HOXA10 was overexpressed in HNSCC cells, while miR-135a-5p was under-expressed. Therefore, low expression of HOXA10 lengthened disease-free survival time and overall survival time. MiR-135a-5p overexpression could inhibit HOXA10 expression by directly targeting HOXA10 3 ' UTR, and the inhibition was more effective than miR-494. HOXA10 suppression inhibited proliferation and enhanced apoptosis of HNSCC cells. In vivo experiments showed that miR-135a-5p could decelerate the growth of tumor cells in mice by downregulating HOXA10 expression. Conclusion: MiR-135a-5p could repress HNSCC cells proliferation and enhance apoptosis by directly targeting HOXA10, implying miR-135a-5p's significance on HNSCC treatment.