Oxysterol binding protein-like 3 (OSBPL3) is a novel driver gene that promotes tumor growth in part through R-Ras/Akt signaling in gastric cancer.
Oxysterol binding protein-like 3 (OSBPL3) is a novel driver gene that promotes tumor growth in part through R-Ras/Akt signaling in gastric cancer.
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DOI：
10.1038/s41598-021-98485-9
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发表时间：
2021-09-28
影响因子：
4.6
通讯作者：
Mimori K
中科院分区：
文献类型：
--
作者：
Hu Q;Masuda T;Koike K;Sato K;Tobo T;Kuramitsu S;Kitagawa A;Fujii A;Noda M;Tsuruda Y;Otsu H;Kuroda Y;Ito S;Oki E;Mimori K
胃癌（Gastric cancer，GC）是世界上最致命的恶性肿瘤之一。为了改善胃癌的预后，迫切需要鉴定新的驱动基因作为治疗靶点。在这里，我们的目的是确定新的驱动基因，并阐明它们在胃癌中的作用。通过对公开基因组数据集的计算机分析，OSBPL 3被鉴定为候选驱动基因。通过RT-qPCR和免疫组织化学分析GC细胞和组织中的OSBPL 3表达。采用体外和体内胃癌细胞模型研究了OSBPL 3在胃癌中的生物学功能和作用机制。还评估了GC患者中OSBPL 3表达与临床结果之间的关联。在具有OSBPL 3 DNA拷贝数增加和启动子低甲基化的GC细胞中检测到OSBPL 3的过表达。OSBPL 3-敲低通过抑制细胞周期进程在体外和体内降低GC细胞生长。此外，活性Ras下拉测定和蛋白质印迹证明OSBPL 3激活GC细胞中的R-Ras/Akt信号通路。在两个GC数据集的临床分析中，高OSBPL 3表达预测预后不良。我们的研究结果表明，OSBPL 3是一种新的驱动基因，刺激R-Ras/Akt信号通路，并在GC患者的潜在治疗靶点。
Gastric cancer (GC) is one of the most lethal malignant tumors. To improve the prognosis of GC, the identification of novel driver genes as therapeutic targets is in urgent need. Here, we aimed to identify novel driver genes and clarify their roles in gastric cancer. OSBPL3 was identified as a candidate driver gene by in silico analysis of public genomic datasets. OSBPL3 expression was analyzed by RT-qPCR and immunohistochemistry in GC cells and tissues. The biological functions and mechanisms of OSBPL3 in GC were examined in vitro and in vivo using GC cells. The association between OSBPL3 expression and clinical outcome in GC patients was also evaluated. Overexpression of OSBPL3 was detected in GC cells with OSBPL3 DNA copy number gains and promoter hypomethylation. OSBPL3-knockdown reduced GC cell growth in vitro and in vivo by inhibiting cell cycle progression. Moreover, an active Ras pull-down assay and western blotting demonstrated that OSBPL3 activates the R-Ras/Akt signaling pathway in GC cells. In a clinical analysis of two GC datasets, high OSBPL3 expression was predictive of a poor prognosis. Our findings suggest that OSBPL3 is a novel driver gene stimulating the R-Ras/Akt signaling pathway and a potential therapeutic target in GC patients.
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影响因子：
14.9
作者：
Kanehisa M;Furumichi M;Sato Y;Ishiguro-Watanabe M;Tanabe M
通讯作者：
Tanabe M
影响因子：
64.5
作者：
Davoli T;Xu AW;Mengwasser KE;Sack LM;Yoon JC;Park PJ;Elledge SJ
通讯作者：
Elledge SJ
影响因子：
16.6
作者：
Saito T;Niida A;Uchi R;Hirata H;Komatsu H;Sakimura S;Hayashi S;Nambara S;Kuroda Y;Ito S;Eguchi H;Masuda T;Sugimachi K;Tobo T;Nishida H;Daa T;Chiba K;Shiraishi Y;Yoshizato T;Kodama M;Okimoto T;Mizukami K;Ogawa R;Okamoto K;Shuto M;Fukuda K;Matsui Y;Shimamura T;Hasegawa T;Doki Y;Nagayama S;Yamada K;Kato M;Shibata T;Mori M;Aburatani H;Murakami K;Suzuki Y;Ogawa S;Miyano S;Mimori K
通讯作者：
Mimori K
影响因子：
11.2
作者：
Nishigaki, M;Aoyagi, K;Sasaki, H
通讯作者：
Sasaki, H
影响因子：
3.7
作者：
Lehto, M;Hynynen, R;Olkkonen, VM
通讯作者：
Olkkonen, VM