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长链非编码RNA VPS9D1-AS1通过Wnt/β-连环蛋白信号通路促进食管鳞状细胞癌进展。

Long noncoding RNA VPS9D1-AS1 promotes esophageal squamous cell carcinoma progression via the Wnt/β-catenin signaling pathway.

作者信息

Ma Liang, Yan Wenyue, Sun Xingwei, Chen Ping

机构信息

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.

出版信息

J Cancer. 2021 Oct 2;12(22):6894-6904. doi: 10.7150/jca.54556. eCollection 2021.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3b1/8517997/c97731fa590a/jcav12p6894g001.jpg

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