Regulation of Oncogenic Targets by miR-99a-3p (Passenger Strand of miR-99a-Duplex) in Head and Neck Squamous Cell Carcinoma
Regulation of Oncogenic Targets by miR-99a-3p (Passenger Strand of miR-99a-Duplex) in Head and Neck Squamous Cell Carcinoma
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DOI：
10.3390/cells8121535
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发表时间：
2019-12-01
期刊：
影响因子：
6
通讯作者：
Seki, Naohiko
中科院分区：
文献类型：
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作者：
Okada, Reona;Koshizuka, Keiichi;Seki, Naohiko
为了鉴定头颈部鳞状细胞癌（HNSCC）中的新致癌靶点，我们分析了HNSCC细胞中的抗肿瘤microRNAs（miRNAs）及其控制的分子网络。基于我们在HNSCC中的miRNA特征，miR-99 a-双链体的两条链（miR-99 a-5 p：引导链，和miR-99 a-3 p：过客链）在癌组织中下调。此外，miR-99 a-5 p和miR-99 a-3 p的低表达显著预测HNSCC的不良预后，并且这些miRNA调节癌细胞的迁移和侵袭。我们以前发现，乘客链的miRNA具有抗肿瘤功能。在此，我们筛选了参与HNSCC发病机制的miR-99 a-3 p控制的癌基因。32个基因被鉴定为miR-99 a-3 p调控基因，10个基因（STAMBP、TIMP 4、TMEM 14 C、CANX、SUV 420 H1、HSP 90 B1、PDIA 3、MTHFD 2、BCAT 1和SLC 22 A15）显著预测5年总生存率。值得注意的是，在这些基因中，STAMBP、TIMP 4、TMEM 14 C、CANX和SUV 420 H1是通过多变量分析的HNSCC的独立预后标志物。我们使用敲低测定进一步研究了STAMBP在HNSCC细胞中的致癌功能。我们的数据表明，HNSCC细胞中表型的侵袭性通过siSTAMBP转染而减弱。此外，异常STAMBP表达检测HNSCC临床标本通过免疫组化。这一策略可能有助于阐明这种疾病的分子发病机制。
To identify novel oncogenic targets in head and neck squamous cell carcinoma (HNSCC), we have analyzed antitumor microRNAs (miRNAs) and their controlled molecular networks in HNSCC cells. Based on our miRNA signature in HNSCC, both strands of the miR-99a-duplex (miR-99a-5p: the guide strand, and miR-99a-3p: the passenger strand) are downregulated in cancer tissues. Moreover, low expression of miR-99a-5p and miR-99a-3p significantly predicts poor prognosis in HNSCC, and these miRNAs regulate cancer cell migration and invasion. We previously showed that passenger strands of miRNAs have antitumor functions. Here, we screened miR-99a-3p-controlled oncogenes involved in HNSCC pathogenesis. Thirty-two genes were identified as miR-99a-3p-regulated genes, and 10 genes (STAMBP, TIMP4, TMEM14C, CANX, SUV420H1, HSP90B1, PDIA3, MTHFD2, BCAT1, and SLC22A15) significantly predicted 5-year overall survival. Notably, among these genes, STAMBP, TIMP4, TMEM14C, CANX, and SUV420H1 were independent prognostic markers of HNSCC by multivariate analyses. We further investigated the oncogenic function of STAMBP in HNSCC cells using knockdown assays. Our data demonstrated that the aggressiveness of phenotypes in HNSCC cells was attenuated by siSTAMBP transfection. Moreover, aberrant STAMBP expression was detected in HNSCC clinical specimens by immunohistochemistry. This strategy may contribute to the clarification of the molecular pathogenesis of this disease.