microRNA-342-3p 通过靶向 FOXQ1 抑制鼻咽癌细胞的侵袭表型。

microRNA-342-3p targets FOXQ1 to suppress the aggressive phenotype of nasopharyngeal carcinoma cells.

机构信息

Department of Rhinology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

BMC Cancer. 2019 Jan 24;19(1):104. doi: 10.1186/s12885-018-5225-5.

BACKGROUND

microRNA (miR)-342-3p is frequently dysregulated in human cancers. In the present study, we aimed to explore the expression, prognostic significance, and biological relevance of miR-342-3p in nasopharyngeal carcinoma (NPC).

METHODS

We examined miR-342-3p expression in 79 paired NPC specimens and corresponding normal tissues and analyzed its prognostic impact on overall survival of NPC patients. Gain- and loss-of-function experiments were conducted to determine the biological roles of miR-342-3p.

RESULTS

Compared with matched normal nasopharyngeal tissues, miR-342-3p was significantly downregulated in NPC (P = 0.0038). Low miR-342-3p expression was significantly correlated with reduced overall survival (P = 0.0084). Ectopic expression of miR-342-3p significantly suppressed proliferation, colony formation, and invasion of NPC cells. In contrast, depletion of miR-342-3p facilitated NPC cell proliferation and invasion. In vivo xenograft studies confirmed that overexpression of miR-342-3p restrained the growth of NPC xenograft tumors. Mechanistically, FOXQ1 served as a functional target of miR-342-3p. There was a significantly negative correlation between miR-342-3p and FOXQ1 expression (r = - 0.487, P = 0.004) in NPC specimens. Overexpression of FOXQ1 rescued the inhibitory effects of miR-342-3p on NPC cell growth and invasion.

CONCLUSIONS

miR-342-3p downregulation predicts poor prognosis in NPC patients and shows suppressive activity against NPC growth and invasion through repression of FOXQ1. Restoration of miR-342-3p may represent a potential therapeutic strategy for NPC.

背景

微小 RNA（miR）-342-3p 在人类癌症中经常失调。在本研究中，我们旨在探索 miR-342-3p 在鼻咽癌（NPC）中的表达、预后意义和生物学相关性。

方法

我们检测了 79 对 NPC 标本和相应正常组织中的 miR-342-3p 表达，并分析了其对 NPC 患者总生存率的预后影响。通过增益和缺失功能实验来确定 miR-342-3p 的生物学作用。

结果

与匹配的正常鼻咽组织相比，miR-342-3p 在 NPC 中明显下调（P=0.0038）。低 miR-342-3p 表达与总生存率降低显著相关（P=0.0084）。miR-342-3p 的异位表达显著抑制 NPC 细胞的增殖、集落形成和侵袭。相反，miR-342-3p 的耗竭促进了 NPC 细胞的增殖和侵袭。体内异种移植研究证实，miR-342-3p 的过表达抑制了 NPC 异种移植瘤的生长。在机制上，FOXQ1 是 miR-342-3p 的功能靶标。在 NPC 标本中，miR-342-3p 与 FOXQ1 表达之间存在显著的负相关（r=-0.487，P=0.004）。FOXQ1 的过表达挽救了 miR-342-3p 对 NPC 细胞生长和侵袭的抑制作用。