UBA2 promotes proliferation of colorectal cancer.
UBA2 promotes proliferation of colorectal cancer.
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DOI：
10.3892/mmr.2018.9613
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发表时间：
2018-12
影响因子：
3.4
通讯作者：
Meng XW
中科院分区：
文献类型：
--
作者：
He P;Sun X;Cheng HJ;Zou YB;Wang Q;Zhou CL;Liu WQ;Hao YM;Meng XW
小泛素样修饰蛋白参与肿瘤发生;然而，家族成员泛素样修饰激活酶2（UBA 2）对结直肠癌的潜在影响和功能尚不清楚。本研究旨在研究UBA 2在体外和体内对结直肠癌细胞增殖的影响。采用逆转录-定量聚合酶链反应（RT-PCR）和免疫组化法检测大肠癌组织中UBA 2 mRNA和蛋白的表达水平。UBA 2在大肠癌组织中的表达水平明显高于癌旁正常组织。UBA 2的表达与大肠癌的分期和预后有关。MTT法和集落形成实验检测大肠癌细胞系的增殖能力。流式细胞术检测UBA 2对大肠癌细胞周期和凋亡的影响，Western blotting检测蛋白表达水平。无胸腺裸鼠用于检查转染的结肠直肠癌细胞在体内形成肿瘤的能力。UBA 2下调可通过调节细胞周期相关蛋白的表达和细胞凋亡抑制大肠癌细胞株的体外和体内增殖。下调UBA 2表达可降低结直肠癌细胞中cyclin B1、B细胞淋巴瘤-2、磷酸化蛋白激酶B和E3泛素蛋白连接酶MDM 2的表达水平，而p21和p27的表达水平升高。UBA 2在结直肠癌的增殖中起重要作用，可作为预测预后的潜在生物标志物和结直肠癌的治疗靶点。
Small ubiquitin-like modifier proteins are involved in tumorigenesis; however, the potential effects and functions of the family member ubiquitin-like modifier-activating enzyme 2 (UBA2) on colorectal cancer are not clear. The present study aimed to examine the effects of UBA2 on the proliferation of colorectal cancer cells in vitro and in vivo. The mRNA and protein expression levels of UBA2 in patients with colorectal cancer were measured by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively. UBA2 expression levels in colorectal cancer tissues were significantly increased compared with the paracancerous normal tissues. The expression of UBA2 was also associated with higher stage colorectal cancer and poor prognosis. MTT and colony formation assays were used to examine proliferation in colorectal cancer cell lines. Flow cytometry was performed to examine the effects of UBA2 on the cell cycle and apoptosis of colorectal cancer cell lines and protein expression levels were examined by western blotting. Athymic nude mice were used to examine the ability of transfected colorectal cancer cells to form tumors in vivo. Downregulation of UBA2 inhibited the proliferation of colorectal cancer cell lines in vitro and in vivo through the regulation of cell cycle associated protein expression and apoptosis. Furthermore, downregulation of UBA2 decreased the expression levels of cyclin B1, B-cell lymphoma-2, phosphorylated protein kinase B and E3 ubiquitin-protein ligase MDM2 in colorectal cancer cells, whereas the expression levels of p21 and p27 were increased. UBA2 was demonstrated to serve an essential role in the proliferation of colorectal cancer and may be used as a potential biomarker to predict prognosis and as a therapeutic target in colorectal cancer.
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