Evaluation of microRNA 92a Expression and Its Target Protein Bim in Colorectal Cancer

Abstract

Background: Colorectal cancer is one of the most commonly diagnosed cancers and leading causes of malignancy-related deaths all over the world. MicroRNAs (miRNAs) can regulate more than 60% of human genes, including tumor-stimulating, and -suppressor genes. Therefore, they can promote cancer development and affect risk of malignancy. miR-92a overexpression in CRC enhances tumor proliferation, invasion, and metastasis through downregulating different pro-apoptosis proteins including Bim. This study aimed to assess the role of plasma miR-92a as non-invasive marker in CRC patients, outline correlation between plasma miR-92a and serum Bim, and determine their correlations with clinicopathological parameters in CRC and adenoma patients. Methods: A total of 54 newly diagnosed CRC patients, 15 colonic adenoma patients, and 15 age-and sex-matched control subjects were recruited in this study. Plasma miR-92a was assayed by TaqMan qRT-PCR and serum Bim was measured by ELISA. Results: Statistically significant overexpression of serum miR-92a was observed in CRC patients as compared to adenoma and control groups (p<0.001 each) and lower serum Bim in CRC patients as compared to adenoma and control groups (p=0.001, p <0.001 respectively). The ROC curve analysis showed excellent AUC for plasma miR-92a in discriminating CRC from control (AUC=0.994), and adenoma (AUC=0.993) groups with highest diagnostic performance in discriminating CRC from controls (at cutoff 1.43, sensitivity 98.1%, specificity 93.9%), and adenoma patients (at cutoff 1.78, sensitivity 92.6%, specificity 93.3%). The diagnostic performance in discriminating early from late CRC was good (at cutoff 15, AUC=0.641, sensitivity 61.2%, specificity 80%). A significant negative correlation was evident between plasma miR-92a and serum Bim both in adenoma and CRC groups (P<0.001 for both). Higher plasma miR-92a expression (r=0.275, p=0.044) and lower serum Bim (r=-0.299, p=0.028) were found to be correlated with late CRC stages. Conclusion: Circulating miR-92a and Bim could be promising, non-invasive diagnostic and prognostic biomarkers in CRC.

Role of Exosomes in Epithelial–Mesenchymal Transition

“…TEXs carry a small protein called MAP17 between tumor cell subsets to enable horizontal spread and EMT. MiRNA-92a-3p is found in significant concentrations in liver and colon cancer . In liver cancer, PTEN expression is suppressed by exosome miRNA-92a-3p and enhances metastasis in colon cancer.…”

“…MiRNA-92a-3p is found in significant concentrations in liver and colon cancer. 45 In liver cancer, PTEN expression is suppressed by exosome miRNA-92a-3p and enhances metastasis in colon cancer. In breast cancer, exosome miRNA-181 enhances metastasis.…”

Influence of Clinical Factors on miR-3613-3p Expression in Colorectal Cancer

“…For colorectal cancer, plenty of relevant microRNAs and their mechanisms were disclosed [ 18 ]; for example, highly expressed miRNA-200 induced epithelial mesenchymal transition (EMT), thus increasing the invasiveness and metastatic activity of CRC [ 19 ], a high expression of miR-762 attenuated cell growth and invasion, which might be accompanied by increased Wnt/beta catenin signaling [ 20 ], higher levels of transcribed miR-92a played a pivotal role in CRC by interacting with anti-apoptotic molecule BCL-2 and contributing to the survival of cancerous cells [ 21 ]; and metastasis of colorectal cancer is also promoted by miR-6716-5p through downregulating NAT10 expression [ 22 ]. In case of microRNA-96, pro-proliferative and anti-apoptotic mechanism in CRC was revealed by downregulating AMPKα2 and upregulating FTO and MYC in the AMPKα2/FTO/m6A/MYC pathway [ 23 ].…”