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Long noncoding RNA SOX2OT promotes the proliferation of pancreatic cancer by binding to FUS.
International Journal of Cancer ( IF 5.7 ) Pub Date : 2020-01-13 , DOI: 10.1002/ijc.32827
Lei Chen 1, 2 , Jingjing Zhang 1, 2 , Qun Chen 1, 2 , Wanli Ge 1, 2 , Lingdong Meng 1, 2 , Xumin Huang 1, 2 , Peng Shen 1, 2 , Hao Yuan 1, 2 , Guodong Shi 1, 2 , Yi Miao 1, 2 , Kuirong Jiang 1, 2
Affiliation  

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors has one of the worst prognoses, and the role of long noncoding RNAs (lncRNAs) in the biological and pathological processes of pancreatic cancer, including tumor cell proliferation, is a popular topic in tumor research. Our previous study revealed the correlation between high levels of the lncRNA-SOX2OT (SOX2OT) with poor survival outcomes. Cell Counting Kit-8, EdU, Flow cytometry and Colony formation assays as well as Xenograft growth of PDAC cells in mice were used for the detection of PDAC cells proliferation progression. Fluorescence in situ hybridization, RNA-binding protein pulldown and RNA immunoprecipitation assays were also used to identify the putative mechanisms of SOX2OT participating in the tumor progression. SOX2OT and its potential downstream targets were verified by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). SOX2OT was confirmed to promote the proliferation of PDAC cells. It was found to directly physically bind to FUS and we also demonstrated that FUS protein stability was affected by binding with SOX2OT and FUS could suppressed PDAC tumor by regulating cell cycle-associated factors CCND1 and p27. Our findings suggest that SOX2OT may act as a tumor promoter in PDAC through physically binding FUS and regulating its downstream cell cycle-associated factors CCND1 and p27. It may serve as an effective target for antitumor treatment for pancreatic cancer.

中文翻译:

长的非编码RNA SOX2OT通过与FUS结合来促进胰腺癌的增殖。

胰腺导管腺癌(PDAC)是最恶性的肿瘤之一,预后最差之一,长非编码RNA(lncRNA)在胰腺癌的生物学和病理过程(包括肿瘤细胞增殖)中的作用是一个热门话题。肿瘤研究。我们先前的研究揭示了高水平的lncRNA-SOX2OT(SOX2OT)与不良的生存结果之间的相关性。使用Cell Counting Kit-8,EdU,流式细胞术和集落形成分析以及小鼠PDAC细胞的异种移植生长来检测PDAC细胞的增殖进程。荧光原位杂交,RNA结合蛋白下拉和RNA免疫沉淀测定法也被用来确定SOX2OT参与肿瘤进程的推测机制。SOX2OT及其潜在的下游靶标已通过Western印迹和定量实时聚合酶链反应(qRT-PCR)进行了验证。证实SOX2OT可以促进PDAC细胞的增殖。已发现直接与FUS物理结合,我们还证明FUS蛋白稳定性受SOX2OT的结合影响,并且FUS可以通过调节细胞周期相关因子CCND1和p27抑制PDAC肿瘤。我们的发现表明,SOX2OT可能通过物理结合FUS并调节其下游细胞周期相关因子CCND1和p27充当PDAC中的肿瘤启动子。它可以作为胰腺癌抗肿瘤治疗的有效靶点。已发现直接与FUS物理结合,我们还证明FUS蛋白稳定性受SOX2OT的结合影响,并且FUS可以通过调节细胞周期相关因子CCND1和p27抑制PDAC肿瘤。我们的发现表明,SOX2OT可能通过物理结合FUS并调节其下游细胞周期相关因子CCND1和p27充当PDAC中的肿瘤启动子。它可以作为胰腺癌抗肿瘤治疗的有效靶点。已发现直接与FUS物理结合,我们还证明FUS蛋白稳定性受SOX2OT的结合影响,并且FUS可以通过调节细胞周期相关因子CCND1和p27抑制PDAC肿瘤。我们的发现表明,SOX2OT可能通过物理结合FUS并调节其下游细胞周期相关因子CCND1和p27充当PDAC中的肿瘤启动子。它可以作为胰腺癌抗肿瘤治疗的有效靶点。我们的发现表明,SOX2OT可能通过物理结合FUS并调节其下游细胞周期相关因子CCND1和p27充当PDAC中的肿瘤启动子。它可以作为胰腺癌抗肿瘤治疗的有效靶点。我们的发现表明,SOX2OT可能通过物理结合FUS并调节其下游细胞周期相关因子CCND1和p27充当PDAC中的肿瘤启动子。它可以作为胰腺癌抗肿瘤治疗的有效靶点。
更新日期:2020-01-13
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