miR-489 is a tumour-suppressive miRNA target PTPN11 in hypopharyngeal squamous cell carcinoma (HSCC).
miR-489 is a tumour-suppressive miRNA target PTPN11 in hypopharyngeal squamous cell carcinoma (HSCC).
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DOI：
10.1038/sj.bjc.6605811
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发表时间：
2010-09-07
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
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作者：
下咽鳞状细胞癌（HSCC）是一种侵袭性恶性肿瘤与预后最差的头颈部癌症之一。更深入地了解相关的分子致癌途径可以帮助改善这种疾病的诊断、治疗和预防。本研究的目的是基于临床hsc标本的miRNA表达特征，鉴定肿瘤抑制microrna (miRNA)，并预测其生物学靶基因。采用茎环实时定量PCR技术对10例人类鳞癌临床样本中365个成熟mirna的表达水平进行了筛选。下调的miRNA用于细胞增殖试验，以鉴定肿瘤抑制miRNA。然后进行全基因组基因表达分析，以鉴定肿瘤抑制miRNA的靶基因。表达分析鉴定出11个上调和31个下调的mirna。下调mirna的功能增益分析显示，miR-489抑制了所有检测的头颈部癌细胞系的细胞生长。编码含有两个Src同源2结构域的细胞质蛋白酪氨酸磷酸酶的基因PTPN11被鉴定为mir -489靶向基因。敲低PTPN11可抑制头颈部SCC细胞的增殖。肿瘤抑制miRNA miR-489及其靶点PTPN11的鉴定可能为了解hsc的潜在分子机制提供新的见解。
Hypopharyngeal squamous cell carcinoma (HSCC) is an aggressive malignancy with one of the worst prognoses among all head and neck cancers. Greater understanding of the pertinent molecular oncogenic pathways could help improve diagnosis, therapy, and prevention of this disease. The aim of this study was to identify tumour-suppressive microRNAs (miRNAs), based on miRNA expression signatures from clinical HSCC specimens, and to predict their biological target genes. Expression levels of 365 human mature miRNAs from 10 HSCC clinical samples were screened using stem-loop real-time quantitative PCR. Downregulated miRNAs were used in cell proliferation assays to identify a tumour-suppressive miRNA. Genome-wide gene expression analyses were then performed to identify the target genes of the tumour-suppressive miRNA. Expression analysis identified 11 upregulated and 31 downregulated miRNAs. Gain-of-function analysis of the downregulated miRNAs revealed that miR-489 inhibited cell growth in all head and neck cancer cell lines examined. The gene PTPN11 coding for a cytoplasmic protein tyrosine phosphatase containing two Src Homology 2 domains was identified as a miR-489-targeted gene. Knockdown of PTPN11 resulted in the inhibition of cell proliferation in head and neck SCC cells. Identification of the tumour-suppressive miRNA miR-489 and its target, PTPN11, might provide new insights into the underlying molecular mechanisms of HSCC.
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影响因子：
6.4
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.
通讯作者：
Califano, Joseph A.
影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
2.6
作者：
Hoffman, HT;Karnell, LH;Fremgen, AM
通讯作者：
Fremgen, AM
DOI：
10.1158/1078-0432.ccr-08-3131
发表时间：
2009-04-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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作者：
Avissar M;Christensen BC;Kelsey KT;Marsit CJ
通讯作者：
Marsit CJ
影响因子：
8.8
作者：
通讯作者：
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