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Long non-coding RNA Loc490 inhibits gastric cancer cell proliferation and metastasis by upregulating RNA-binding protein Quaking

机译:长期非编码RNA LOC490通过上调RNA结合蛋白Quaking来抑制胃癌细胞增殖和转移

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摘要

Gastric cancer (GC) is one of the most common malignant tumor types worldwide. Long non-coding RNAs (lncRNAs) have important epigenetic effects, including altering the proliferation and metastasis of malignant tumors. We used gene chip technology to search for lncRNAs that were differentially expressed in GC and metastatic lymph node tissues compared with adjacent normal tissues. The lncRNA Loc490 and the RNA-binding protein Quaking (QKI) were downregulated in GC tissues and lymph node metastases compared with normal tissues, and the levels of these two genes correlated positively with one another. Loc490 expression correlated negatively with lymph node metastasis and veinerve invasion, while it correlated positively with overall and disease-free survival. In vitro, Loc490 post-translationally enhanced the expression of QKI and suppressed the expression of epithelial-mesenchymal transition-related molecules. Overexpression of Loc490 inhibited GC cell proliferation, invasion and metastasis and exerted strong antitumor effects in vivo, while silencing of QKI antagonized these effects. A potential binding site between Loc490 and QKI was detected through bioinformatics analysis and confirmed through RNA immunoprecipitation and mutant analyses. Our results suggest that lncRNA Loc490 inhibits GC cell proliferation and metastasis by upregulating RNA-binding protein QKI.
机译:胃癌(GC)是全球最常见的恶性肿瘤类型之一。长期非编码RNA(LNCRNA)具有重要的表观遗传效应,包括改变恶性肿瘤的增殖和转移。我们使用基因芯片技术在与相邻的正常组织相比,在GC和转移性淋巴结组织中寻找差异表达的LNCRNA。与正常组织相比,在GC组织和淋巴结转移中下调LNCRNA Loc490和RNA结合蛋白Quaking(QKI),并且这两个基因的水平彼此正呈正相关。 Loc490表达与淋巴结转移和静脉/神经侵袭负相关,而其呈整体和无病生存率呈正相关。体外,LOM490翻译后增强了QKI的表达,并抑制了上皮 - 间充质过渡相关分子的表达。 LOM490的过度表达抑制了GC细胞增殖,侵袭和转移,并在体内施加强烈的抗肿瘤作用,同时QKI对抗这些效果。通过生物信息学分析检测到LOC490和QKI之间的潜在结合位点,并通过RNA免疫沉淀和突变分析证实。我们的研究结果表明,通过上调RNA结合蛋白质QKI,LNCRNA Loc490抑制GC细胞增殖和转移。

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