Department of Digestive Diseases, Henan University Huaihe Hospital, Kaifeng, China.
Department of Respiratory Medicine, Henan University Huaihe Hospital, Kaifeng, China.
Artif Cells Nanomed Biotechnol. 2020 Dec;48(1):572-583. doi: 10.1080/21691401.2020.1726937.
Gastric cancer (GC) is a malignant tumour with high lethality. Accruing evidence elucidates the critical adjusting role of long non-coding RNA (lncRNAs) in human cancers. DDX11 antisense RNA 1 (DDX11-AS1) was previously found to be involved in GC pathogenesis. However, the precise molecular mechanisms of DDX11-AS1 need to be further investigated. In this study, we found that DDX11-AS1 expression was up-regulated in GC tumour tissues and cells. Increased DDX11-AS1 expression was associated with advanced TNM stage and lymph node metastasis. Functionally, knockdown of DDX11-AS1 repressed cell proliferation and clone formation, while induced cell cycle arrest and apoptosis. As expected, DDX11-AS1 overexpression displayed the opposite effect. Mechanically, DDX11-AS1 enhanced SPC18 expression through acting as a ceRNA for miR-873-5p. Furthermore, the inhibitory effect of DDX11-AS1 silencing on malignant biological behaviour of GC cells was attenuated by either miR-873-5p inhibitor or SEC11A up-regulation. Moreover, suppression of DDX11-AS1 also decreased GC tumorigenesis . In conclusion, DDX11-AS1 may serve as an oncogene in GC progression by sponging miR-873-5p and promoting SPC18 expression, providing a new insight into the mechanisms of DDX11-AS1 and elucidating a promising therapy target in GC.
胃癌(GC)是一种致死率很高的恶性肿瘤。越来越多的证据表明,长链非编码 RNA(lncRNAs)在人类癌症中起着关键的调节作用。DDX11 反义 RNA 1(DDX11-AS1)先前被发现与 GC 发病机制有关。然而,DDX11-AS1 的精确分子机制仍需进一步研究。在本研究中,我们发现 DDX11-AS1 在 GC 肿瘤组织和细胞中表达上调。DDX11-AS1 表达增加与较晚的 TNM 分期和淋巴结转移有关。功能上,敲低 DDX11-AS1 抑制细胞增殖和克隆形成,而诱导细胞周期停滞和细胞凋亡。正如预期的那样,DDX11-AS1 的过表达则显示出相反的效果。机制上,DDX11-AS1 通过作为 miR-873-5p 的 ceRNA 增强 SPC18 的表达。此外,DDX11-AS1 沉默对 GC 细胞恶性生物学行为的抑制作用被 miR-873-5p 抑制剂或 SEC11A 上调所减弱。此外,抑制 DDX11-AS1 也降低了 GC 的肿瘤发生。总之,DDX11-AS1 可能通过海绵吸附 miR-873-5p 并促进 SPC18 表达,从而促进 GC 进展,充当 GC 进展中的癌基因,为 DDX11-AS1 的机制提供了新的见解,并阐明了 GC 中一个有前途的治疗靶点。