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在体外和体内，miR-512-5p通过靶向端粒酶阳性头颈部鳞状细胞癌中的hTERT抑制肿瘤生长。

miR-512-5p suppresses tumor growth by targeting hTERT in telomerase positive head and neck squamous cell carcinoma in vitro and in vivo.

作者信息

Li Jun, Lei Han, Xu Yong, Tao Ze-Zhang

机构信息

Department of Otolaryngology-Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China; Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China.

Hubei key laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

出版信息

PLoS One. 2015 Aug 10;10(8):e0135265. doi: 10.1371/journal.pone.0135265. eCollection 2015.

DOI:10.1371/journal.pone.0135265
PMID:26258591
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4530866/
Abstract

Telomerase activation has very important implications for head and neck squamous cell carcinoma (HNSCC), but the regulatory mechanisms of telomerase in HNSCC remain unclear. In our present study, we found that miR-512-5P was markedly downregulated in telomerase-positive HNSCC cell lines. Both in vitro and in vivo assays revealed that miR-512-5P mimic attenuated HNSCC cell proliferation, and tumor growth in nude mice, which exerts its tumor suppressor function through elevated apoptosis, inhibition of the telomerase activity, decrease of telomere-binding proteins and shortening of telomere length by human telomerase reverse transcriptase (hTERT) downregulation. Furthermore, the dual-luciferase reporter gene assay results demonstrated that hTERT was a direct target of miR-512-5P. We conclude that the frequently miR-512-5P overexpression can regulate hTERT and function as a tumor suppressor in HNSCC. Therefore, miR-512-5P may serve as a potential therapeutic agent for miR-based HNSCC therapy.

摘要

端粒酶激活对头颈部鳞状细胞癌（HNSCC）具有非常重要的意义，但端粒酶在HNSCC中的调控机制仍不清楚。在我们目前的研究中，我们发现miR-512-5P在端粒酶阳性的HNSCC细胞系中显著下调。体外和体内实验均表明，miR-512-5P模拟物可减弱HNSCC细胞增殖以及裸鼠体内肿瘤生长，其通过提高细胞凋亡、抑制端粒酶活性、减少端粒结合蛋白以及通过下调人端粒酶逆转录酶（hTERT）缩短端粒长度来发挥其肿瘤抑制功能。此外，双荧光素酶报告基因检测结果表明hTERT是miR-512-5P的直接靶点。我们得出结论，miR-512-5P的频繁过表达可调节hTERT并在HNSCC中作为肿瘤抑制因子发挥作用。因此，miR-512-5P可能作为基于miR的HNSCC治疗的潜在治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b3/4530866/206212617a40/pone.0135265.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b3/4530866/58d4ef093618/pone.0135265.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b3/4530866/f56d3e65c67b/pone.0135265.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b3/4530866/4dc0caae4d8f/pone.0135265.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b3/4530866/206212617a40/pone.0135265.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b3/4530866/58d4ef093618/pone.0135265.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b3/4530866/f56d3e65c67b/pone.0135265.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b3/4530866/4dc0caae4d8f/pone.0135265.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b3/4530866/206212617a40/pone.0135265.g004.jpg

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