The potent tumor suppressor miR-497 inhibits cancer phenotypes in nasopharyngeal carcinoma by targeting ANLN and HSPA4L.
The potent tumor suppressor miR-497 inhibits cancer phenotypes in nasopharyngeal carcinoma by targeting ANLN and HSPA4L.
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DOI：
10.18632/oncotarget.5651
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发表时间：
2015-11-03
期刊：
影响因子：
--
通讯作者：
Murata M
中科院分区：
文献类型：
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作者：
Wang S;Mo Y;Midorikawa K;Zhang Z;Huang G;Ma N;Zhao W;Hiraku Y;Oikawa S;Murata M
鼻咽癌是东南亚特有的一种预后不良的恶性肿瘤。我们使用微阵列分析了鼻咽癌细胞的microRNAs(MiRNAs)，并通过定量RT-PCR对结果进行了验证。结果显示，相对于非癌鼻咽上皮(NNE)，鼻咽癌组织中有7个miRNAs显著上调，6个miRNAs显著下调。鼻咽癌患者血浆中miR-497的表达也明显低于非肿瘤对照组。MiR-497在组织和血浆中的表达下调一致，提示miR-497可作为鼻咽癌的诊断生物标志物。对miR-497对肿瘤表型影响的功能分析表明，将miR-497模拟基因导入鼻咽癌细胞可抑制细胞的生长和迁移，并诱导细胞凋亡。裸鼠皮下移植的转基因细胞显示miR-497显著抑制肿瘤生长。在鼻咽癌组织中过表达的miR-497的两个潜在靶点ANLN和HSPA4L在鼻咽癌细胞中被miR-497模拟的miR-497负调控。沉默ANLN和HSPA4L可抑制鼻咽癌细胞的增殖和迁移，并诱导细胞凋亡。我们的发现表明miR-497是一种有效的肿瘤抑制因子，它通过靶向ANLN和HSPA4L来抑制鼻咽癌的肿瘤表型。
Nasopharyngeal carcinoma (NPC) is a malignancy with poor prognosis that is endemic to Southeast Asia. We profiled microRNAs (miRNAs) of NPCs using microarrays and confirmed the results by quantitative RT-PCR. The results revealed that seven miRNAs were significantly up-regulated, and six miRNAs were down-regulated, in NPC tissues relative to noncancerous nasopharyngeal epithelia (NNE). Expression of miR-497 was also significantly reduced in the plasma of NPC patients relative to the plasma of noncancerous control patients. The concordant down-regulation of miR-497 in tissues and plasma suggested that miR-497 could be used as a diagnostic biomarker for NPC. Functional analyses of the effect of miR-497 on cancer phenotypes revealed that transfection of miR-497 mimic into NPC cells suppressed cell growth and migration and induced apoptosis. Subcutaneous xenografts of transfected cells in nude mice demonstrated that miR-497 significantly inhibited tumor growth. Two potential targets of miR-497, ANLN (anillin, actin-binding protein) and HSPA4L (heat shock 70 kDa protein 4–like), both of which were overexpressed in NPC tissues, were negatively regulated by miR-497 mimic in NPC cell lines. Silencing of ANLN and HSPA4L suppressed cell proliferation and migration and induced apoptosis in NPC cells. Our findings indicate that miR-497 is a potent tumor suppressor that inhibits cancer phenotypes by targeting ANLN and HSPA4L in NPC.