Department of Gastroenterology, Bethune First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Department of Pathology, Bethune First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Mol Med Rep. 2018 Dec;18(6):5552-5562. doi: 10.3892/mmr.2018.9613. Epub 2018 Oct 30.
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.
小泛素样修饰蛋白参与肿瘤的发生；然而，家族成员泛素样修饰酶激活酶 2（UBA2）对结直肠癌的潜在影响和功能尚不清楚。本研究旨在研究 UBA2 对结直肠癌细胞体外和体内增殖的影响。通过逆转录定量聚合酶链反应和免疫组织化学分别测量了患者结直肠癌中 UBA2 的 mRNA 和蛋白表达水平。与癌旁正常组织相比，结直肠癌组织中 UBA2 的表达水平显著增加。UBA2 的表达与较高的结直肠癌分期和不良预后相关。MTT 和集落形成测定用于检测结直肠癌细胞系的增殖。流式细胞术用于检测 UBA2 对结直肠癌细胞系细胞周期和凋亡的影响，并通过蛋白质印迹法检测蛋白表达水平。使用裸鼠研究转染的结直肠癌细胞在体内形成肿瘤的能力。下调 UBA2 通过调节细胞周期相关蛋白表达和凋亡抑制了结直肠癌细胞系的体外和体内增殖。此外，下调 UBA2 降低了结直肠癌细胞中环细胞素 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 MDM2 的表达水平，而 p21 和 p27 的表达水平增加。UBA2 被证明在结直肠癌细胞的增殖中起重要作用，可作为预测预后的潜在生物标志物，并作为结直肠癌的治疗靶点。
