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. 2019 Jan;17(1):55-62.
doi: 10.3892/ol.2018.9623. Epub 2018 Oct 26.

MicroRNA 214 inhibits adipocyte enhancer-binding protein 1 activity and increases the sensitivity of chemotherapy in colorectal cancer

Shouchao Li  1 , Chengren Li  1 , Zhiming Fang  1
Affiliations

MicroRNA 214 inhibits adipocyte enhancer-binding protein 1 activity and increases the sensitivity of chemotherapy in colorectal cancer

Shouchao Li et al. Oncol Lett. 2019 Jan.

Abstract

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.

Keywords: adipocyte enhancer-binding protein 1; chemotherapy; colorectal cancer; microRNA 214; prognosis.

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Figures

Figure 1.
Figure 1.
Immunohistochemistry of colorectal cancer tissues and adjacent non-cancerous tissues. Representative tissue sections with different immunointensities of adipocyte enhancer-binding protein 1. Histological type: 3+, strong expression; 2+, moderate expression; 1+, weak expression; 0, negative expression. Magnification, ×400.
Figure 2.
Figure 2.
Kaplan-Meier survival analysis of primary colorectal cancer patients (n=62) following surgical resection with high AEBP1 expression (n=39) and low AEBP1 expression (n=23). (A) OS following surgery and (B) DFS following surgery. AEBP1, adipocyte enhancer-binding protein 1; OS, overall survival; DFS, disease-free survival.
Figure 3.
Figure 3.
(A) Cell proliferation detection in groups using the Cell Counting kit-8 method and apoptosis detection. (B) Cell apoptosis ratio in HT-29 cells following cell transfection and oxaliplatin treatment. Experimental group absorbance optical density values are significantly lower than those of the other 2 groups (**P<0.05). No statistically significant differences were observed between the negative and the blank control groups. (C) Relative luciferase activity analyses. The relative luciferase activity of the vector (+) group was set as 1 (compared with WT miR-214, *P<0.05). (D) HT-29 cell lysates were obtained for western blot analysis of AEBP1 following transfection. β-actin served as a control. WT, wild type; Mut, mutant; miR-214, microRNA-214; AEBP1, adipocyte enhancer-binding protein 1.
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