MicroRNA alterations in head and neck squamous cell carcinoma.

MicroRNA alterations in head and neck squamous cell carcinoma.
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DOI:
10.1002/ijc.23831
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发表时间:
2008-12-15
影响因子:
6.4
通讯作者:
Califano, Joseph A.
Califano, Joseph A.
中科院分区:
医学1区
文献类型:
--
作者:
Chang, Steven S.;Jiang, Wei Wen;Smith, Ian;Poeta, Luana M.;Begum, Shahnaz;Glazer, Chad;Shan, Shannon;Westra, William;Sidransky, David;Califano, Joseph A.

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MicroRNA(miRs)是一种小的非编码RNA分子(~22个核苷酸),其调节转录后基因表达。目前,还没有一个全面的研究,他们在小学HNSCC的作用。为了确定miR在头颈部鳞状细胞癌(HNSCC)中的作用,我们筛选了HNSCC原代组织和细胞系中改变的microRNA表达。然后,我们进一步测试了特定mir改变的功能影响。通过微阵列分析4种原代HNSCC、4种正常粘膜对照和4种HNSCC细胞系的初始筛选的成熟microRNA表达。使用微阵列显著性分析(SAM)确定显著性。SAM检测发现9种microRNA在肿瘤组织中表达上调或下调,包括mir-21、let-7、18、29 c、142- 3 p、155、146 b(高表达)和494(低表达)。通过qRT-PCR验证Mir-21。通过生长测定进行功能验证,进一步验证mir-21。将mir-21转染到JHU-011和JHU-012细胞系中显示,相对于对照,在72小时时细胞生长增加39%(p<0.05)。将抑制剂转染到JHU-O 12细胞系中显示在72小时时相对于对照,细胞生长降低92%(p<0.05)。此外,在mir-21抑制剂转染后48小时,JHU-012细胞的流式细胞术分析显示细胞色素c释放的统计学显著增加和细胞凋亡增加。这些差异表达的microRNA可能是HNSCC中潜在的新癌基因和抑癌基因。Mir-21是头颈癌中的一种推定的致癌microRNA。
MicroRNAs (mirs) are small non-coding RNA molecules (~22 nucleotides) that regulate post-transcriptional gene expression. Currently, there has not been a comprehensive study of their role in primary HNSCC. To determine the role of mirs in head and neck squamous cell carcinoma (HNSCC), we screened for altered microRNA expression in HNSCC primary tissue and cell lines. We then further tested the functional impact of alterations of specific mirs. An initial screening of 4 primary HNSCC, 4 normal mucosal controls and 4 HNSCC cell lines were analyzed for mature microRNA expression by microarray. Significance was determined using Significance Analysis of Microarrays (SAM). Nine microRNAs were found by SAM to be up-regulated or down-regulated in tumor tissue including mir-21,let-7,18,29c,142-3p,155,146b(over-expressed) and 494(under-expressed). Mir-21 was validated by qRT-PCR. Functional validation by growth assays was performed, further validating mir-21. Transfection of mir-21 into JHU-011 and JHU-012 cell lines showed a 39% increase in cell growth at 72 hrs relative to controls (p<.05). Transfection of the inhibitor into JHU-O12 cell lines showed a 92% decrease in cell growth relative to controls at 72hrs (p<.05). In addition, flow cytometry analysis of JHU-012 cells 48 hrs after mir-21 inhibitor transfection showed a statistically significantly increase in cytochrome c release and increased apoptosis. These differentially expressed microRNAs may be of interest as potential novel oncogenes and tumor suppressor genes in HNSCC. Mir-21 is a putative oncogenic microRNA in head and neck cancer.
幼稚,效应子和记忆CD8 T细胞的miRNA分析。
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期刊: PLOS ONE
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发表时间: 2006-10-15
影响因子: 4
作者:
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