Role of microRNAs in colorectal adenoma progression

Abstract Colorectal cancer (CRC) survival rates are stage related and majority of patients (75%) with CRC have sporadic of the disease which is in form of adenoma. Most of colorectal adenocarcinomas precursors are adenomatous polyps. Moreover, CRC appears to be an age related disease and studies have shown that mutations in mtDNA appear to accumulate with age because of inadequate repair. Also, oxidative stress has been shown to affect mitochondrial proteins resulting in a decrease of mitochondrial function associated with the precursor lesions of cancer. Recent findings suggest that the mitochondrion has sequences that code for certain miRNA which can regulate different pathways frequently dysregulated in cancer including colorectal cancer (CRC). Isolation of mitochondria RNA from colorectal precancerous polyps, cancer, and normal adjacent tissue samples was performed and assessed for gene expression differences using quantitative reverse transcription PCR. We demonstrate that mitochondria genome expression of miRNAs miR-24, miR 181, miR 210, and miR 21 in colorectal tissue samples varies during disease progression. Expression of microRNAs 24, 181, and 210 progressively increased from the earliest precancerous polyp to cancer. In addition, miR-210 and miR-181 expression increased 3 folds in villous adenomas when compared to tubular adenoma. Meanwhile, miR 21 increased progressively in adenoma tissues but decreased almost 4 folds in cancer tissues when compared to villous adenoma tissue. These results suggest miRNAs within the mitochondria genome may regulate important mitochondrial functional pathways leading to a more favorable environment for transformation or progression of adenomas to cancerous tumors. Citation Format: LaShanale M. Wallace, Aneese F. Chaudhry, Karen I. Aikhionbare, Xuebiao Yao, Felix O. Aikhionbare. Role of microRNAs in colorectal adenoma progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1804.