Down-regulated lncRNA SLC25A5-AS1 facilitates cell growth and inhibits apoptosis via miR-19a-3p/PTEN/PI3K/AKT signalling pathway in gastric cancer
Down-regulated lncRNA SLC25A5-AS1 facilitates cell growth and inhibits apoptosis via miR-19a-3p/PTEN/PI3K/AKT signalling pathway in gastric cancer
复制标题
胃癌中下调的lncRNA SLC25A5-AS1通过miR-19a-3p/PTEN/PI3K/AKT信号通路促进细胞生长并抑制细胞凋亡
DOI：
10.1111/jcmm.14200
复制
发表时间：
2019-04-01
影响因子：
5.3
通讯作者：
Ju, Shaoqing
中科院分区：
文献类型：
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作者：
Li, Xiwen;Yan, Xin;Ju, Shaoqing
越来越多的证据表明长链非编码RNA（lncRNA）在胃癌（GC）中的重要作用。然而，它们在GC中的大部分作用和机制仍然很大程度上未知。在本研究中，我们研究了lncRNA SLC25A5-AS1在肿瘤发生中的作用，并探讨了其在GC中的潜在机制。结果表明， GC中SLC25A5-AS1显着低于癌旁正常组织，且与肿瘤大小、TNM分期及淋巴结转移显着相关。此外，SLC25A5-AS1 可以抑制 GC 细胞增殖，体外诱导 G1/G1 细胞周期停滞和细胞凋亡，以及体内 GC 生长。双荧光素酶报告基因检测 证实了SLC25A5-AS1与miR-19a-3p之间的直接相互作用，拯救实验表明，共转染miR-19a-3p模拟物和pcDNA-SLC25A5-AS1可以部分恢复GC细胞增殖能力并抑制细胞凋亡。机制分析进一步发现SLC25A5-AS1可能作为竞争性内源RNA (ceRNA)，参与 miR-19a-3p 靶基因 PTEN 表达的去抑制，并通过 PI3K/AKT 信号通路调节 GC 中的恶性表型。综上所述，这项研究表明 SLC25A5-AS1 在 GC 中下调，并在 GC 进展中发挥抑制作用。此外，它可以作为 ceRNA 来调节细胞 通过 miR-19a-3p/PTEN/PI3K/AKT 信号通路调节行为。因此，SLC25A5-AS1可能作为GC癌症治疗的潜在靶点。
Mounting evidence has illustrated the vital roles of long non-coding RNAs (lncRNAs in gastric cancer (GC). Nevertheless, the majority of their roles and mechanisms in GC are still largely unknown. In this study, we investigate the roles of lncRNA SLC25A5-AS1 on tumourigenesis and explore its potential mechanisms in GC. The results showed that the expressions of SLC25A5-AS1 in GC were significantly lower than that of adjacent normal tissues, which were significantly associated with tumour size, TNM stage and lymph node metastasis. Moreover, SLC25A5-AS1 could inhibit GC cell proliferation, induce G1/G1 cell cycle arrest and cell apoptosis in vitro, as well as GC growth in vivo. Dual-luciferase reporter assay confirmed the direct interaction between SLC25A5-AS1 and miR-19a-3p, rescue experiment showed that co-transfection miR-19a-3p mimics and pcDNA-SLC25A5-AS1 could partially restore the ability of GC cell proliferation and the inhibition of cell apoptosis. The mechanism analyses further found that SLC25A5-AS1 might act as a competing endogenous RNAs (ceRNA), which was involved in the derepression of PTEN expression, a target gene of miR-19a-3p, and regulate malignant phenotype via PI3K/AKT signalling pathway in GC. Taken together, this study indicated that SLC25A5-AS1 was down-regulated in GC and functioned as a suppressor in the progression of GC. Moreover, it could act as a ceRNA to regulate cellular behaviours via miR-19a-3p/PTEN/PI3K/AKT signalling pathway. Thus, SLC25A5-AS1 might be served as a potential target for cancer therapeutics in GC.