miR-383 inhibits hepatocellular carcinoma cell proliferation via targeting APRIL
miR-383 inhibits hepatocellular carcinoma cell proliferation via targeting APRIL
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DOI：
10.1007/s13277-015-4071-1
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发表时间：
2016-02-01
期刊：
影响因子：
--
通讯作者：
Wang, Feng
中科院分区：
文献类型：
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作者：
Chen, Lin;Guan, Haitao;Wang, Feng
越来越多的证据表明，microRNA（miRNAs），一类小的非编码RNA，经常在人类恶性肿瘤中失调，并在包括癌细胞增殖在内的多种生物学过程中发挥关键作用。在此，我们研究了miR-383在64例肝细胞癌（HCC）组织和4个HCC细胞系中的表达模式，发现miR-383在HCC组织和细胞系中表达下调。此外，miR-383在HCC中的表达与肿瘤大小和肿瘤淋巴结转移（TNM）分期显著相关。Kaplan-Meier分析显示，miR-383表达降低与HCC患者总体生存率低相关。此外，考克斯回归分析表明，miR-383是HCC患者的独立预后因素。功能研究表明，miR-383异位表达可显著抑制肝癌细胞的体外增殖，并诱导细胞周期阻滞和细胞凋亡。荧光素酶报告基因检测进一步证实了肿瘤坏死因子（TNF）超家族成员增殖诱导配体（APRIL）是miR-383的新靶基因。随后的研究显示，在HCC组织中，miR-383的表达与APRIL信使RNA（mRNA）的表达呈负相关。此外，重组人APRIL（rhAPRIL）能够挽救miR-383抑制的肝癌细胞增殖。综上所述，我们目前的研究提供了第一个证据，证明miR-383在HCC中减少，并与HCC患者的肿瘤进展和预后相关。此外，我们的研究结果证实，miR-383可能通过下调APRIL表达部分抑制HCC细胞增殖。因此，这项研究可能提供一个有希望的策略，通过靶向与miR-383-APRIL轴在肝癌的治疗。
Mounting evidence has shown that microRNAs (miRNAs), a class of small non-coding RNAs, are frequently deregulated in human malignancies and have pivotal roles in diverse biological processes including cancer cell proliferation. Herein, we investigated the expression pattern of miR-383 in 64 hepatocellular carcinoma (HCC) tissues and 4 HCC cell lines and found that miR-383 was downregulated in HCC tissues and cell lines. Moreover, miR-383 expression in HCC was significantly correlated with tumor size and tumor-node-metastasis (TNM) stage. Kaplan-Meier analysis showed that decreased miR-383 expression was associated with poor overall survival of HCC patients. In addition, Cox regression analysis indicated that miR-383 was an independent prognostic factor for HCC patients. Then, functional studies demonstrated that ectopic miR-383 expression could significantly suppress the in vitro proliferation of HCC cells, as well as induce cell cycle arrest and cell apoptosis. Luciferase reporter assay further identified that a proliferation-inducing ligand (APRIL), a member in the tumor necrosis factor (TNF) superfamily, was a novel target gene for miR-383. Subsequent investigation revealed that miR-383 expression was inversely correlated with APRIL messenger RNA (mRNA) expression in HCC tissues. Besides, recombinant human APRIL (rhAPRIL) could rescue HCC cell proliferation inhibited by miR-383. Taken together, our present study provided the first evidence that miR-383 was decreased in HCC and associated with tumor progression and prognosis of HCC patients. Furthermore, our findings confirmed that miR-383 might inhibit HCC cell proliferation partially via downregulating APRIL expression. Thus, this study might provide a promising strategy by targeting with the miR-383-APRIL axis in the treatment of HCC.