Zhang Haixiong, Cao Hui, Xu Dadao, Zhu Kang
Department of Otorhinolaryngology, Head and Neck Surgery, the First Affiliated Hospital of Xi'an Medical College, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Department of Otorhinolaryngology, Head and Neck Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Onco Targets Ther. 2016 Jun 16;9:3579-88. doi: 10.2147/OTT.S105470. eCollection 2016.
MicroRNAs have been confirmed to be a group of important regulators during the pathogenesis of nasopharyngeal carcinoma (NPC). This study confirmed that the expression of microRNA-92a (miR-92a) was significantly upregulated in NPC as compared to noncancerous nasopharyngeal epithelial tissues. Furthermore, high expression of miR-92a was observed in all NPC cell lines, especially in high metastatic cell lines. Clinical analysis indicated that high expression of miR-92a was associated with adverse clinicopathological features including the advanced tumor-node-metastasis stage and distant metastasis, and conferred poor prognosis of patients. In vitro assays showed that miR-92a overexpression potentiated the migration and invasion of 6-10B cells, and miR-92a silencing reduced the number of migrated and invaded 5-8F cells. Phosphatase and tensin homolog (PTEN) was confirmed as a direct downstream target of miR-92a in NPC cells. Otherwise, alteration of miR-92a expression regulated PTEN/AKT pathway in NPC cells. Mechanistically, miR-92a exerted its promoting effects on the metastatic behaviors of NPC cells through suppressing PTEN/AKT pathway. Taken together, this study demonstrates that miR-92a is a promising prognostic biomarker for patients with NPC, and may be a potential therapeutic target to prevent the metastasis of NPC.
微小RNA已被证实是鼻咽癌(NPC)发病机制中的一组重要调节因子。本研究证实,与非癌性鼻咽上皮组织相比,微小RNA-92a(miR-92a)在NPC中的表达显著上调。此外,在所有NPC细胞系中均观察到miR-92a的高表达,尤其是在高转移细胞系中。临床分析表明,miR-92a的高表达与不良临床病理特征相关,包括肿瘤-淋巴结-转移晚期和远处转移,并预示患者预后不良。体外试验表明,miR-92a过表达增强了6-10B细胞的迁移和侵袭能力,而miR-92a沉默则减少了5-8F细胞的迁移和侵袭数量。磷酸酶和张力蛋白同源物(PTEN)被证实为NPC细胞中miR-92a的直接下游靶点。此外,miR-92a表达的改变调节了NPC细胞中的PTEN/AKT通路。从机制上讲,miR-92a通过抑制PTEN/AKT通路对NPC细胞的转移行为发挥促进作用。综上所述,本研究表明miR-92a是NPC患者有前景的预后生物标志物,可能是预防NPC转移的潜在治疗靶点。