Deep sequencing-based microRNA expression signatures in head and neck squamous cell carcinoma: dual strands of pre-miR-150 as antitumor miRNAs.
Deep sequencing-based microRNA expression signatures in head and neck squamous cell carcinoma: dual strands of pre-miR-150 as antitumor miRNAs.
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DOI：
10.18632/oncotarget.16327
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发表时间：
2017-05-02
期刊：
影响因子：
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通讯作者：
Seki N
中科院分区：
文献类型：
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作者：
Koshizuka K;Nohata N;Hanazawa T;Kikkawa N;Arai T;Okato A;Fukumoto I;Katada K;Okamoto Y;Seki N
我们采用RNA测序技术构建了头颈部鳞状细胞癌（HNSCC）的microRNA（miRNA）表达特征。我们的签名显示，共有160个miRNA（44个上调和116个下调）在癌组织中异常表达。miR-150- 5 p（引导链miRNA）和miR-150- 3 p（过客链miRNA）的表达在癌组织中显著沉默，表明这两种miRNA在HNSCC细胞中充当抗肿瘤miRNA。成熟miRNA、miR-150- 5 p和miR-150- 3 p的异位表达抑制癌细胞的侵袭性。通过Kaplan-Meier生存曲线分析，miR-150- 5 p和miR-150- 3 p的低表达预测HNSCC患者的总生存期显著较短（P = 0.0091和P = 0.0386）。我们发现HNSCC细胞中整合素α3（ITGA 3）、整合素α6（ITGA 6）和腱生蛋白C（TNC）受到这些miRNA的协同调节。使用siRNA的敲低测定显示ITGA 3、ITGA 6和TNC在HNSCC细胞中充当促癌基因。此外，ITGA 3、ITGA 6和TNC改变与总生存率显著降低相关（分别为P = 0.0177、P = 0.0237和P = 0.026）。基于HNSCC的miRNA表达特征，pre-150的双链（miR-150- 5 p和miR-150- 3 p）作为抗肿瘤miRNA发挥作用。抗肿瘤miR-150介导的RNA网络的鉴定可能为HNSCC的发病机制提供新的见解。
We adopted into RNA-sequencing technologies to construct the microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Our signature revealed that a total of 160 miRNAs (44 upregulated and 116 downregulated) were aberrantly expressed in cancer tissues. Expression of miR-150-5p (guide strand miRNA) and miR-150-3p (passenger strand miRNA) were significantly silenced in cancer tissues, suggesting both miRNAs act as antitumor miRNAs in HNSCC cells. Ectopic expression of mature miRNAs, miR-150-5p and miR-150-3p inhibited cancer cell aggressiveness. Low expression of miR-150-5p and miR-150-3p predicted significantly shorter overall survival in patients with HNSCC (P = 0.0091 and P = 0.0386) by Kaplan–Meier survival curves analyses. We identified that integrin α3 (ITGA3), integrin α6 (ITGA6), and tenascin C (TNC) were coordinately regulated by these miRNAs in HNSCC cells. Knockdown assays using siRNAs showed that ITGA3, ITGA6 and TNC acted as cancer promoting genes in HNSCC cells. Moreover, ITGA3, ITGA6, and TNC alterations were associated with significantly poorer overall survival (P = 0.0177, P = 0.0237, and P = 0.026, respectively). Dual strands of pre-150 (miR-150-5p and miR-150-3p) functioned as antitumor miRNAs based on the miRNA expression signature of HNSCC. Identification of antitumor miR-150-mediated RNA networks may provide novel insights into pathogenesis of HNSCC.