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SOX2OT/miR-194-5p轴通过抑制上皮-间质转化来调节胃癌细胞的增殖和迁移。

The SOX2OT/miR-194-5p axis regulates cell proliferation and mobility of gastric cancer through suppressing epithelial-mesenchymal transition.

作者信息

Wei Ruqiong, Ding Can, Rodrìguez Raquel Alarcòn, Del Mar Requena Mullor Marìa

机构信息

Department of Nursing, Physiotherapy and Medicine, Universidad de Almería, Almería 04120, Spain.

出版信息

Oncol Lett. 2018 Nov;16(5):6361-6368. doi: 10.3892/ol.2018.9433. Epub 2018 Sep 12.

Abstract

Recent studies reported that long noncoding RNAs (LncRNAs) were involved in tumorigenesis of various human cancer types, including gastric cancer (GC) through targeting microRNAs (miRNAs/miRs). The present study investigated the biological functions of LncRNA SOX2 overlapping transcript (SOX2OT)/miR-194-5p axis and its underlying mechanism in the tumor progression of GC. The results showed that relative expression of LncRNA SOX2OT was highly upregulated while the expression of miR-194-5p was down-regulated in GC tissues and cell lines (MGC-803, SGC-7901, MKN-74). Knockdown of SOX2OT inhibited cell proliferation, invasion and migration of GC cells (MGC803, MKN-74) through reducing epithelial-mesenchymal transition (EMT). Moreover, miR-194-5p was predicted to be one of the targets of SOX2OT through bioinformatics analysis and was verified by luciferase reporter assay. miR-194-5p expression was negatively regulated by SOX2OT expression in GC cells and miR-194-5p inhibitor was found to counteract the inhibitory effects of SOX2OT short hairpin (sh)RNA on cell proliferation and mobility through enhancing EMT in GC cells. Taken together, the experiments revealed that knockdown of SOX2OT inhibited cell proliferation and mobility through suppressing EMT via targeting miR-194-5p in GC. In addition, results from experiments showed that knockdown of SOX2OT suppressed GC tumor growth and matrix metalloproteinase (MMP)-2 and MMP-9 expression through inhibiting EMT. Besides that, relative expression of miR-194-5p was increased in sh-SOX2OT group compared with sh-NC group. In summary, our study elucidated that the SOX2OT/miR-194-5p axis participated in the tumor progression of GC through regulation of EMT both and . Hence, targeting the SOX2OT/miR-194-5p axis may aid in establishing novel strategies for therapy of GC.

摘要

近期研究报道,长链非编码RNA(LncRNAs)通过靶向微小RNA(miRNAs/miRs)参与了包括胃癌(GC)在内的多种人类癌症类型的肿瘤发生过程。本研究调查了LncRNA SOX2重叠转录本(SOX2OT)/miR-194-5p轴在GC肿瘤进展中的生物学功能及其潜在机制。结果显示,在GC组织和细胞系(MGC-803、SGC-7901、MKN-74)中,LncRNA SOX2OT的相对表达显著上调,而miR-194-5p的表达下调。敲低SOX2OT通过减少上皮-间质转化(EMT)抑制了GC细胞(MGC803、MKN-74)的增殖、侵袭和迁移。此外,通过生物信息学分析预测miR-194-5p是SOX2OT的靶标之一,并通过荧光素酶报告基因检测进行了验证。在GC细胞中,miR-194-5p的表达受到SOX2OT表达的负调控,并且发现miR-194-5p抑制剂可通过增强GC细胞中的EMT来抵消SOX2OT短发夹(sh)RNA对细胞增殖和迁移的抑制作用。综上所述这些实验表明,敲低SOX2OT通过在GC中靶向miR-194-5p抑制EMT来抑制细胞增殖和迁移。此外,实验结果表明敲低SOX2OT通过抑制EMT抑制了GC肿瘤生长以及基质金属蛋白酶(MMP)-2和MMP-9的表达。除此之外,与sh-NC组相比,sh-SOX2OT组中miR-194-5p的相对表达增加。总之,我们的研究阐明了SOX2OT/miR-194-5p轴通过在体内和体外调节EMT参与了GC的肿瘤进展。因此,靶向SOX2OT/miR-194-5p轴可能有助于建立新的GC治疗策略。

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