Kandhavelu Jeyalakshmi, Subramanian Kumar, Khan Amber, Omar Aadilah, Ruff Paul, Penny Clement
Oncology Division, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, South Africa.
Microrna. 2019;8(1):68-75. doi: 10.2174/2211536607666180803100246.
Globally, colorectal cancer (CRC) is the third most common cancer in women and the fourth most common cancer in men. Dysregulation of small non-coding miRNAs have been correlated with colon cancer progression. Since there are increasing reports of candidate miRNAs as potential biomarkers for CRC, this makes it important to explore common miRNA biomarkers for colon cancer. As computational prediction of miRNA targets is a critical initial step in identifying miRNA: mRNA target interactions for validation, we aim here to construct a potential miRNA network and its gene targets for colon cancer from previously reported candidate miRNAs, inclusive of 10 up- and 9 down-regulated miRNAs from tissues; and 10 circulatory miRNAs.
The gene targets were predicted using DIANA-microT-CDS and TarBaseV7.0 databases. Each miRNA and its targets were analyzed further for colon cancer hotspot genes, whereupon DAVID analysis and mirPath were used for KEGG pathway analysis.
We have predicted 874 and 157 gene targets for tissue and serum specific miRNA candidates, respectively. The enrichment of miRNA revealed that particularly hsa-miR-424-5p, hsa-miR-96-5p, hsa-miR-1290, hsa-miR-224, hsa-miR-133a and has-miR-363-3p present possible targets for colon cancer hallmark genes, including BRAF, KRAS, EGFR, APC, amongst others. DAVID analysis of miRNA and associated gene targets revealed the KEGG pathways most related to cancer and colon cancer. Similar results were observed in mirPath analysis. A new insight gained in the colon cancer network pathway was the association of hsa-mir-133a and hsa-mir-96-5p with the PI3K-AKT signaling pathway. In the present study, target prediction shows that while hsa-mir-424-5p has an association with mostly 10 colon cancer hallmark genes, only their associations with MAP2 and CCND1 have been experimentally validated.
These miRNAs and their targets require further evaluation for a better understanding of their associations, ultimately with the potential to develop novel therapeutic targets.
在全球范围内，结直肠癌（CRC）是女性中第三大常见癌症，男性中第四大常见癌症。小型非编码miRNA的失调与结肠癌进展相关。由于越来越多关于候选miRNA作为CRC潜在生物标志物的报道，探索结肠癌常见的miRNA生物标志物变得很重要。由于miRNA靶标的计算预测是识别用于验证的miRNA：mRNA靶标相互作用的关键初始步骤，我们旨在从先前报道的候选miRNA构建一个潜在的miRNA网络及其结肠癌基因靶标，包括来自组织的10个上调和9个下调的miRNA；以及10个循环miRNA。
使用DIANA-microT-CDS和TarBaseV7.0数据库预测基因靶标。进一步分析每个miRNA及其靶标与结肠癌热点基因的关系，随后使用DAVID分析和mirPath进行KEGG通路分析。
我们分别预测了组织和血清特异性miRNA候选物的874个和157个基因靶标。miRNA的富集分析表明，特别是hsa-miR-424-5p、hsa-miR-96-5p、hsa-miR-1290、hsa-miR-224、hsa-miR-133a和has-miR-363-3p呈现出结肠癌标志性基因的可能靶标，包括BRAF、KRAS、EGFR、APC等。对miRNA及其相关基因靶标的DAVID分析揭示了与癌症和结肠癌最相关的KEGG通路。在mirPath分析中观察到类似结果。在结肠癌网络通路中获得的一个新见解是hsa-mir-133a和hsa-mir-96-5p与PI3K-AKT信号通路的关联。在本研究中，靶标预测表明，虽然hsa-mir-424-5p主要与10个结肠癌标志性基因相关，但只有它们与MAP2和CCND1的关联已通过实验验证。
这些miRNA及其靶标需要进一步评估，以更好地理解它们之间的关联，最终有可能开发新的治疗靶点。
