Wang Jie, Lei Changjiang, Shi Pingping, Teng Huaixiang, Lu Lixiang, Guo Hailong, Wang Xiuqin
Gynaecology Clinic, People's Hospital of Rizhao, Rizhao, China.
Department of Oncology, the Second Affiliated Hospital of Jianghan University, Wuhan, China.
Front Oncol. 2021 Aug 23;11:714652. doi: 10.3389/fonc.2021.714652. eCollection 2021.
Dysregulation of long noncoding RNA (lncRNA) is implicated in the initiation and progression of various tumors, including endometrial cancer (EC). However, the mechanism of lncRNAs in EC tumorigenesis and progression remains largely unexplored. In this work, we identified a novel lncRNA DC-STAMP domain-containing 1-antisense 1 (DCST1-AS1), which is highly upregulated and correlated with poor survival in EC patients. Overexpression of DCST1-AS1 significantly enhanced EC cell proliferation, colony formation, migration, and invasion and promoted tumor growth of EC . Mechanistically, DCST1-AS1 mediated EC progression by inducing the expression of homeobox B5 (HOXB5) and cell adhesion molecule 1 (CADM1), acting as a competing endogenous RNA for microRNA-665 (miR-665) and microRNA-873-5p (miR-873-5p), respectively. In addition, we found that the expression of miR-665 and miR-873-5p was significantly downregulated, while HOXB5 and CADM1 expression levels were increased in EC tissues. Taken together, our findings support the important role of DCST1-AS1 in EC progression, and DCST1-AS1 may be used as a prognostic biomarker as well as a potential therapeutic target for EC.
长链非编码RNA(lncRNA)的失调与包括子宫内膜癌(EC)在内的各种肿瘤的发生和发展有关。然而,lncRNAs在EC肿瘤发生和发展中的机制仍 largely unexplored。在这项研究中,我们鉴定了一种新型lncRNA含DC-STAMP结构域1反义1(DCST1-AS1),其在EC患者中高度上调且与不良生存相关。DCST1-AS1的过表达显著增强了EC细胞的增殖、集落形成、迁移和侵袭,并促进了EC的肿瘤生长。机制上,DCST1-AS1通过诱导同源盒B5(HOXB5)和细胞粘附分子1(CADM1)的表达介导EC进展,分别作为微小RNA-665(miR-665)和微小RNA-873-5p(miR-873-5p)的竞争性内源RNA。此外,我们发现miR-665和miR-873-5p的表达在EC组织中显著下调,而HOXB5和CADM1的表达水平升高。综上所述,我们的研究结果支持DCST1-AS1在EC进展中的重要作用,并且DCST1-AS1可能用作EC的预后生物标志物以及潜在的治疗靶点。