Ma Liang, Yan Wenyue, Sun Xingwei, Chen Ping
Department of Oncology, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, The First People's Hospital of Yancheng, Yancheng, Jiangsu , China.
Department of Intervention, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
J Cancer. 2021 Oct 2;12(22):6894-6904. doi: 10.7150/jca.54556. eCollection 2021.
The VPS9D1 antisense RNA1 (VPS9D1-AS1, lncRNA MYU) can act as an oncogene or an antioncogene in different malignancies. In the present study, we demonstrated that VPS9D1-AS1 is significantly upregulated in esophageal squamous cell carcinoma (ESCC) and assessed its biological function and clinical prognosis. RNA-sequencing was conducted in four pairs of ESCC tissues and normal adjacent tissues (NATs). Compared with controls, lncRNA VPS9D1-AS1 was highly expressed in ESCC tissues, cell lines and plasma. VPS9D1-AS1 upregulation significantly correlated with the histopathological grade and clinical stage of ESCC. Analyses revealed poor prognosis in ESCC patients with high VPS9D1-AS1 expression. VPS9D1-AS1 knockdown led to the inhibition of tumor proliferation, migration, and invasion and vitro. VPS9D1-AS1 silencing downregulated the Wnt/β-catenin signaling pathways by acting on key proteins such as β-catenin and c-Myc. However, the expressions of these proteins increased after the addition of pathway agonist CT99021. Therefore, taken together VPS9D1-AS1 is highly expressed in ESCC and its expression can lead to poor prognosis. In conclusion, this study suggested that VPS9D1-AS1 acts as a vital part in facilitating ESCC progression and can be a potential biomarker for the diagnosis of patients with ESCC.
VPS9D1反义RNA1(VPS9D1-AS1,长链非编码RNA MYU)在不同的恶性肿瘤中既可以作为癌基因,也可以作为抑癌基因发挥作用。在本研究中,我们证明VPS9D1-AS1在食管鳞状细胞癌(ESCC)中显著上调,并评估了其生物学功能和临床预后。对四对ESCC组织及其癌旁正常组织(NATs)进行了RNA测序。与对照组相比,lncRNA VPS9D1-AS1在ESCC组织、细胞系和血浆中高表达。VPS9D1-AS1的上调与ESCC的组织病理学分级和临床分期显著相关。分析显示,VPS9D1-AS1高表达的ESCC患者预后较差。敲低VPS9D1-AS1可导致体外肿瘤增殖、迁移和侵袭受到抑制。VPS9D1-AS1沉默通过作用于关键蛋白如β-连环蛋白和c-Myc下调Wnt/β-连环蛋白信号通路。然而,添加通路激动剂CT99021后,这些蛋白的表达增加。因此,综合来看,VPS9D1-AS1在ESCC中高表达,其表达可导致预后不良。总之,本研究表明VPS9D1-AS1在促进ESCC进展中起重要作用,可作为ESCC患者诊断的潜在生物标志物。