Abstract
To elucidate novel aspects of the molecular pathogenesis of colorectal cancer (CRC), we have created a new microRNA (miRNA) expression signature based on RNA-sequencing. Analysis of the signature showed that 84 miRNAs were upregulated, and 70 were downregulated in CRC tissues. Interestingly, our signature indicated that both guide and passenger strands of some miRNAs were significantly dysregulated in CRC tissues. These findings support our earlier data demonstrating the involvement of miRNA passenger strands in cancer pathogenesis. Our study focused on downregulated miR-490-3p and investigated its tumor-suppressive function in CRC cells. We successfully identified a total of 38 putative oncogenic targets regulated by miR-490-3p in CRC cells. Among these targets, the expression of three genes (IRAK1: p = 0.0427, FUT1: p = 0.0468, and GPRIN2: p = 0.0080) significantly predicted 5-year overall survival of CRC patients. Moreover, we analyzed the direct regulation of IRAK1 by miR-490-3p, and its resultant oncogenic function in CRC cells. Thus, we have clarified a part of the molecular pathway of CRC based on the action of tumor-suppressive miR-490-3p. This new miRNA expression signature of CRC will be a useful tool for elucidating new molecular pathogenesis in this disease.
Highlights
Colorectal cancer (CRC) is one of the most common cancers of the digestive system, as it constitutes approximately 10% of all diagnosed cancers, with almost 900,000 deaths annually [1,2]
We focused on IRAK1 as an oncogenic tar regulation in colorectal cancer (CRC) cells
We investigated direct regulation of IRAK1 by miR-490-3p in CRC cells
Summary
Colorectal cancer (CRC) is one of the most common cancers of the digestive system, as it constitutes approximately 10% of all diagnosed cancers, with almost 900,000 deaths annually [1,2]. The expansion of treatment options and the spread of diagnostic systems have greatly contributed to improving the prognosis of patients with CRC [2,3,4]. For patients with advanced cancer with metastasis, the 5-year survival rate is approximately. 14%, and improving the prognosis of these patients is an important clinical issue [3]. The number of young people (under the age of 50) with colorectal cancer is increasing, especially rectal cancer and left-sided colon cancer [2].
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