Medical College of Nanchang University, Nanchang, People's Republic of China.
Department of Surgery, Jiangxi Tumor Hospital, Nanchang, People's Republic of China.
Am J Physiol Gastrointest Liver Physiol. 2020 Jan 1;318(1):G10-G22. doi: 10.1152/ajpgi.00405.2018. Epub 2019 Aug 21.
Gastric cancer (GC) is one of the most common cancers in the world and remains a heavy burden of health worldwide. Adenylate cyclase 3 () is a widely expressed membrane-associated protein in human tissues and has been identified to be a new molecular target of GC. Long noncoding RNAs have a substantial influence on tumorigenesis and progression of tumors by binding to microRNAs. Therefore, this study is to clarify the mechanism by which LINC00319 sponges micro RNA-335-5p () to influence the development of GC. Initially, microarray analysis identified GC-related differentially expressed LINC00319 and for this study. The interaction was confirmed that LINC00319 interacted with to regulate . Next, SGC-7901 cells presenting with the lowest LINC00319 expression and the highest expression were transfected with LINC00319, inhibitor, or vector to examine their roles in growth and metastasis of GC cells, which was further ascertained by in vivo experiments. LINC00319 was upregulated and was downregulated in GC cells. LINC00319 overexpression, inhibitor, or overexpression was shown to significantly elevate the expression of cyclin-dependent kinase 4 and metastasis associated 1, decrease that of growth arrest-specific 1, and promote tumor growth and metastasis by increasing proliferation and migration and reducing cell apoptosis. Importantly, it was found that overexpressed exerted its tumor suppressive role in GC through downregulating . Collectively, LINC00319 expedited growth and metastasis of GC by upregulating -mediated . This study is carried out based on in vivo and in vitro studies in mice and gastric cancer (GC) cells with the aim of clarifying the role of LINC00319 on GC growth and metastasis, which associated with micro RNA-335-5p-mediated adenylate cyclase 3. Altogether, we identified LINC00319 to be a potential therapy to treat GC.
胃癌(GC)是世界上最常见的癌症之一,仍然是全球健康的沉重负担。腺苷酸环化酶 3()是人类组织中广泛表达的膜相关蛋白,已被确定为 GC 的新分子靶标。长链非编码 RNA 通过与 microRNA 结合对肿瘤发生和肿瘤进展有重大影响。因此,本研究旨在阐明 LINC00319 通过海绵 microRNA-335-5p()影响 GC 发展的机制。最初,通过微阵列分析鉴定了与 GC 相关的差异表达 LINC00319 和 用于本研究。证实了 LINC00319 与 相互作用以调节 。接下来,转染 LINC00319、抑制剂或 载体的 SGC-7901 细胞表达最低的 LINC00319 和最高的 表达,进一步通过体内实验证实了它们在 GC 细胞生长和转移中的作用。LINC00319 在 GC 细胞中上调,而 在 GC 细胞中下调。LINC00319 过表达、抑制剂或 过表达显着提高了细胞周期蛋白依赖性激酶 4 和转移相关 1 的表达,降低了生长停滞特异性 1 的表达,并通过增加增殖和迁移以及减少细胞凋亡来促进肿瘤生长和转移。重要的是,发现过表达的 通过下调 发挥其在 GC 中的肿瘤抑制作用。本研究通过在体内和体外进行小鼠和胃癌(GC)细胞研究,旨在阐明 LINC00319 对 GC 生长和转移的作用,这与 microRNA-335-5p 介导的腺苷酸环化酶 3 有关。总的来说,我们确定 LINC00319 是治疗 GC 的潜在疗法。