Tumour-suppressive microRNA-874 contributes to cell proliferation through targeting of histone deacetylase 1 in head and neck squamous cell carcinoma.
Tumour-suppressive microRNA-874 contributes to cell proliferation through targeting of histone deacetylase 1 in head and neck squamous cell carcinoma.
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DOI：
10.1038/bjc.2013.122
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发表时间：
2013-04-30
影响因子：
8.8
通讯作者：
Seki N
中科院分区：
文献类型：
--
作者：
Nohata N;Hanazawa T;Kinoshita T;Inamine A;Kikkawa N;Itesako T;Yoshino H;Enokida H;Nakagawa M;Okamoto Y;Seki N
我们最近对microRNA（miRNA）表达特征的研究表明microRNA-874（miR-874）在上颌窦鳞状细胞癌（MSSCC）中显著下调，并且在人类癌症中被认为是肿瘤抑制性miRNA。本研究的目的是研究miR-874在癌细胞中的功能意义，并确定新的miR-874介导的癌症途径和头颈部鳞状细胞癌（HNSCC）的相关基因。使用成熟miR-874进行功能获得研究以研究HNSCC细胞系（SAS和FaDu）中的细胞增殖和细胞周期分布。为了鉴定miR-874介导的分子通路和靶点，我们利用基因表达分析和计算机数据库分析。进行功能丧失测定以研究miR-874靶基因的功能意义。与正常对应上皮相比，miR-874在HNSCC组织（包括口腔、咽和喉SCC）中的表达水平显著下调。miR-874在SAS和FaDu细胞系中的恢复揭示了细胞增殖的显著抑制以及G2/M停滞和细胞凋亡的诱导。我们的表达数据和计算机分析表明，miR-874调节细胞周期途径。此外，组蛋白去乙酰化酶1（HDAC 1）是miR-874调控的候选靶点。荧光素酶报告基因分析表明，miR-874直接调控HDAC 1。HDAC 1基因的沉默显着抑制SAS细胞的细胞增殖，并诱导G2/M期阻滞和细胞凋亡。miR-874的下调是HNSCC中的常见事件。miR-874作为肿瘤抑制因子，直接靶向HDAC 1。对肿瘤抑制性miRNA介导的癌症通路的认识为HNSCC肿瘤发生的潜在机制提供了新的见解，并为该疾病提出了新的治疗策略。
Our recent studies of microRNA (miRNA) expression signature demonstrated that microRNA-874 (miR-874) was significantly downregulated in maxillary sinus squamous cell carcinoma (MSSCC), and a putative tumour-suppressive miRNA in human cancers. Our aim of this study was to investigate the functional significance of miR-874 in cancer cells and to identify novel miR-874-mediated cancer pathways and responsible genes in head and neck squamous cell carcinoma (HNSCC). Gain-of-function studies using mature miR-874 were performed to investigate cell proliferation and cell cycle distribution in HNSCC cell lines (SAS and FaDu). To identify miR-874-mediated molecular pathways and targets, we utilised gene expression analysis and in silico database analysis. Loss-of-function assays were performed to investigate the functional significance of miR-874 target genes. Expression levels of miR-874 were significantly downregulated in HNSCC tissues (including oral, pharyngeal and laryngeal SCCs) compared with normal counterpart epithelia. Restoration of miR-874 in SAS and FaDu cell lines revealed significant inhibition of cell proliferation and induction of G2/M arrest and cell apoptosis. Our expression data and in silico analysis demonstrated that miR-874 modulated the cell cycle pathway. Moreover, histone deacetylase 1 (HDAC1) was a candidate target of miR-874 regulation. Luciferase reporter assays showed that miR-874 directly regulated HDAC1. Silencing of the HDAC1 gene significantly inhibited cell proliferation and induced G2/M arrest and cell apoptosis in SAS cells. Downregulation of miR-874 was a frequent event in HNSCC. miR-874 acted as a tumour suppressor and directly targeted HDAC1. Recognition of tumour-suppressive miRNA-mediated cancer pathways provides new insights into the potential mechanisms of HNSCC oncogenesis and suggests novel therapeutic strategies for the disease.
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影响因子：
14.9
作者：
Kanehisa M;Goto S;Sato Y;Furumichi M;Tanabe M
通讯作者：
Tanabe M
DOI：
10.1111/j.1349-7006.2001.tb02153.x
发表时间：
2001-12
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Choi JH;Kwon HJ;Yoon BI;Kim JH;Han SU;Joo HJ;Kim DY
通讯作者：
Kim DY
影响因子：
8.8
作者：
通讯作者：
--
DOI：
10.1038/nrg2485
发表时间：
2009-01
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
--
作者：
Kinoshita T;Hanazawa T;Nohata N;Kikkawa N;Enokida H;Yoshino H;Yamasaki T;Hidaka H;Nakagawa M;Okamoto Y;Seki N
通讯作者：
Seki N