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长链非编码 RNA LINC00629 通过竞争性结合 miR-196b-5p 上调 AQP4 来抑制胃癌的进展。

Long noncoding RNA LINC00629 restrains the progression of gastric cancer by upregulating AQP4 through competitively binding to miR-196b-5p.

机构信息

Departement of Gastrointestinal Surgery, General Hospital of Ningxia Medical University, Yinchuan, China.

Departement of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan, China.

出版信息

J Cell Physiol. 2020 Mar;235(3):2973-2985. doi: 10.1002/jcp.29203. Epub 2019 Oct 31.

Abstract

Gastric cancer continues to be a common cancer in the world with high incidence and mortality. Accumulating evidence has implicated long noncoding RNAs (lncRNAs) in gastric cancer progression. Here, this study identified the potential role of a novel lncRNA, LINC00629 in gastric cancer and to elucidate the underlying mechanism. Initially, microarray-based gene expression profiling of gastric cancer was employed to identify differentially expressed genes. Next, the expression of LINC00629, microRNA-196b-5p (miR-196b-5p) and aquaporin 4 (AQP4) in clinical gastric cancer tissues was determined and the cell line presenting with the lowest LINC00629 expression was selected. The interaction among LINC00629, miR-196b-5p, and AQP4 was identified. Expression of LINC00629, miR-196b-5p, and AQP4 in gastric cancer cells were altered and then biological behaviors of gastric cancer cells were assessed by 5-ethynyl-2'-deoxyuridine and Transwell assays. Tumor formation in vivo was evaluated in nude mice. In gastric cancer, expression of LINC00629 and AQP4 was downregulated, and expression of miR-196b-5p was upregulated. Proliferation, invasion, and migration of gastric cancer cells were reduced after overexpression of LINC00629. LINC00629 competitively bound to miR-196b-5p, while AQP4 was a target of miR-196b-5p. Either downregulating miR-196b-5p or upregulating AQP4 could restrain the development of gastric cancer in vitro. LINC00629 overexpression repressed the growth of transplanted tumors in vivo. Taken together, LINC00629 competitively bound to miR-196b-5p to upregulate AQP4 expression, thereby inhibiting gastric cancer progression. Therefore, understanding of this mechanism may help to improve gastric cancer treatment.

摘要

胃癌仍然是世界上发病率和死亡率较高的常见癌症。越来越多的证据表明,长链非编码 RNA(lncRNA)在胃癌的进展中起作用。在这里,本研究确定了一种新型 lncRNA LINC00629 在胃癌中的潜在作用,并阐明了其潜在机制。首先,采用基于微阵列的基因表达谱分析方法鉴定胃癌差异表达基因。接下来,检测了临床胃癌组织中 LINC00629、miR-196b-5p(miR-196b-5p)和水通道蛋白 4(AQP4)的表达,并选择表达 LINC00629 最低的细胞系。鉴定了 LINC00629、miR-196b-5p 和 AQP4 之间的相互作用。改变胃癌细胞中 LINC00629、miR-196b-5p 和 AQP4 的表达,然后通过 5-乙炔基-2'-脱氧尿苷和 Transwell 分析评估胃癌细胞的生物学行为。在裸鼠体内评估肿瘤形成。在胃癌中,LINC00629 和 AQP4 的表达下调,而 miR-196b-5p 的表达上调。过表达 LINC00629 后,胃癌细胞的增殖、侵袭和迁移减少。LINC00629 竞争性结合 miR-196b-5p,而 AQP4 是 miR-196b-5p 的靶标。下调 miR-196b-5p 或上调 AQP4 均可抑制体外胃癌的发展。LINC00629 的过表达抑制体内移植瘤的生长。总之,LINC00629 竞争性结合 miR-196b-5p 上调 AQP4 表达,从而抑制胃癌的进展。因此,对这一机制的了解可能有助于改善胃癌的治疗。

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