Li Shouchao, Li Chengren, Fang Zhiming
Department of Anorectal Surgery, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China.
Oncol Lett. 2019 Jan;17(1):55-62. doi: 10.3892/ol.2018.9623. Epub 2018 Oct 26.
The present study aimed to analyze adipocyte enhancer-binding protein 1 (AEBP1) expression in colorectal cancer (CRC), with a focus on its possible molecular mechanisms, in order to provide novel insight into the clinical treatment of CRC. Immunohistochemistry (IHC) was used to detect AEBP1 expression in 62 CRC tissues. Kaplan-Meier survival curves were used to analyze AEBP1 expression and the postoperative disease-free survival (DFS) and overall survival (OS) rates of CRC patients. HT-29 cells were treated with oxaliplatin to detect cell proliferation and apoptosis following a Cell Counting kit-8. Through bioinformatics prediction, microRNA 214 (miR214) was identified as an upstream microRNA of AEBP1 that regulates its expression. IHC revealed that the expression of AEBP1 in CRC tissues was significantly higher than that in adjacent healthy tissues, and that it is associated with Tumor-Node-Metastasis stage, recurrence and metastasis. The DFS and OS rates of patients with a low AEBP1 expression were significantly higher than those in patients with a high expression (P<0.05). Following depletion of AEBP1 and treatment with oxaliplatin, the HT-29 cell proliferation was lower than that of the blank control and the negative control groups. However, the cell apoptosis rate was higher than that of the control group at 72 h (P<0.05). Bioinformatics prediction revealed that miR-214 is negatively associated with AEBP1 expression, and co-transfection and luciferase report gene tests revealed that AEBP1 is a target gene of miR-214. Therefore, AEBP1 may become a novel treatment for CRC patients with chemoresistance and may act through the upstream miR-214 to participate in the progression of a tumor.
本研究旨在分析脂肪细胞增强子结合蛋白1（AEBP1）在结直肠癌（CRC）中的表达情况，并重点关注其可能的分子机制，以便为CRC的临床治疗提供新的见解。采用免疫组织化学（IHC）方法检测62例CRC组织中AEBP1的表达。利用Kaplan-Meier生存曲线分析AEBP1表达与CRC患者术后无病生存期（DFS）和总生存期（OS）率的关系。用奥沙利铂处理HT-29细胞，通过细胞计数试剂盒-8检测细胞增殖和凋亡情况。通过生物信息学预测，确定微小RNA 214（miR214）是调节AEBP1表达的上游微小RNA。IHC结果显示，AEBP1在CRC组织中的表达明显高于相邻健康组织，且与肿瘤-淋巴结-转移分期、复发和转移相关。AEBP1低表达患者的DFS和OS率明显高于高表达患者（P<0.05）。在敲低AEBP1并用奥沙利铂处理后，HT-29细胞的增殖低于空白对照组和阴性对照组。然而，在72小时时，细胞凋亡率高于对照组（P<0.05）。生物信息学预测显示，miR-214与AEBP1表达呈负相关，共转染和荧光素酶报告基因检测显示AEBP1是miR-214的靶基因。因此，AEBP1可能成为对化疗耐药的CRC患者的一种新的治疗方法，并可能通过上游的miR-214参与肿瘤的进展。
