Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong, China.
Department of Clinical Laboratory, Traditional Chinese Medicine Hospital, Kunshan, China.
J Cell Mol Med. 2019 Apr;23(4):2920-2932. doi: 10.1111/jcmm.14200. Epub 2019 Feb 22.
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.
越来越多的证据表明，长链非编码 RNA（lncRNAs）在胃癌（GC）中发挥着重要作用。然而，它们在 GC 中的大多数作用和机制仍在很大程度上未知。在这项研究中，我们研究了 lncRNA SLC25A5-AS1 在肿瘤发生中的作用，并探索了其在 GC 中的潜在机制。结果表明，GC 中 SLC25A5-AS1 的表达明显低于相邻正常组织，且与肿瘤大小、TNM 分期和淋巴结转移显著相关。此外，SLC25A5-AS1 可抑制 GC 细胞的增殖，诱导体外 G1/G1 细胞周期阻滞和细胞凋亡，并抑制体内 GC 生长。双荧光素酶报告基因实验证实了 SLC25A5-AS1 与 miR-19a-3p 的直接相互作用，挽救实验表明，共转染 miR-19a-3p 模拟物和 pcDNA-SLC25A5-AS1 可部分恢复 GC 细胞增殖能力和抑制细胞凋亡的能力。机制分析进一步发现，SLC25A5-AS1 可能作为一种竞争性内源 RNA（ceRNA），通过 PI3K/AKT 信号通路参与 miR-19a-3p 靶基因 PTEN 表达的去抑制，从而调节 GC 中的恶性表型。总之，本研究表明 SLC25A5-AS1 在 GC 中下调，并在 GC 的进展中起抑制作用。此外，它可以作为 ceRNA 通过 miR-19a-3p/PTEN/PI3K/AKT 信号通路调节细胞行为。因此，SLC25A5-AS1 可能成为 GC 癌症治疗的潜在靶点。
