Tumor suppressor miR-24 restrains gastric cancer progression by downregulating RegIV.

Tumor suppressor miR-24 restrains gastric cancer progression by downregulating RegIV.
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肿瘤抑制因子 miR-24 通过下调 RegIV 抑制胃癌进展

DOI:
10.1186/1476-4598-13-127
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发表时间:
2014-05-28
期刊:
影响因子:
37.3
通讯作者:
Yang Q
Yang Q
中科院分区:
医学1区
文献类型:
--
作者:
Duan Y;Hu L;Liu B;Yu B;Li J;Yan M;Yu Y;Li C;Su L;Zhu Z;Xiang M;Liu B;Yang Q

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microRNA是一类小分子非编码RNA,通过调节多个靶点来调节多种细胞过程,从而促进或抑制恶性行为的发生。越来越多的证据表明miR-24在人类肿瘤发生中起重要作用。然而,其确切的生物学作用在很大程度上仍然难以捉摸。本研究探讨了miR-24在胃癌(GC)中的作用。采用qRT-PCR方法检测胃癌组织中miR-24的表达,并与癌旁组织和胃癌细胞进行比较。合成短的单链或双链RNA寡核苷酸和慢病毒载体用于调控胃癌细胞中miR-24的表达,以研究其在体外和体内的功能。胃癌组织中miR-24表达显著下调,且与肿瘤分化程度相关。miR-24在SGC-7901胃癌细胞中的异位表达通过诱导细胞周期阻滞于G 0/G1期和促进细胞凋亡,抑制了胃癌细胞的体外增殖、迁移和侵袭能力以及体内致瘤性。此外,我们还发现RegIV是miR-24的靶点,并证明miR-24通过结合其3′端非翻译区来调控RegIV的表达。miR-24作为一种新的胃癌抑制因子,其抑癌活性可能与抑制靶基因RegIV有关。这些发现表明miR-24作为GC治疗靶点的可能性。
microRNAs are small noncoding RNAs that modulate a variety of cellular processes by regulating multiple targets, which can promote or inhibit the development of malignant behaviors. Accumulating evidence suggests miR-24 plays important roles in human carcinogenesis. However, its precise biological role remains largely elusive. This study examined the role of miR-24 in gastric cancer (GC). The expression of miR-24 in GC tissues compared with matched non-tumor tissues and GC cells was detected by qRT-PCR. Synthetic short single or double stranded RNA oligonucleotides and lentiviral vectors were used to regulate miR-24 expression in GC cells to investigate its function in vitro and in vivo. miR-24 was significantly downregulated in GC tissues compared with matched non-tumor tissues and was associated with tumor differentiation. Ectopic expression of miR-24 in SGC-7901 GC cells suppressed cell proliferation, migration and invasion in vitro as well as tumorigenicity in vivo by inducing cell cycle arrest in G0/G1 phase and promoting cell apoptosis. Furthermore, we identified RegIV as a target of miR-24 and demonstrated that miR-24 regulated RegIV expression via binding its 3′ untranslated region. miR-24 functions as a novel tumor suppressor in GC and the anti-oncogenic activity may involve its inhibition of the target gene RegIV. These findings suggest the possibility for miR-24 as a therapeutic target in GC.
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