The Promising Role of Let-7 Microrna in Colorectal Cancer: Practical Points for Clinicians

Nikolaos Margetis, Athanassios Kotsinas and Theodoros Mariolis-Sapsakos

1Athens Euroclinic, Department of Gastroenterology, University of Athens, Greece
Molecular Carcinogenesis Group, Laboratory of Histology and Embryology, Medical School, University of Athens, Greece
Assistant Professor, Laboratory of Histology and Embryology, Medical School, University of Athens, Greece
Aghioi Anargyroi” Hospital, Athens, Greece
Assistant Professor, Laboratory of Anatomy, School of Nursing, University of Athens, Greece

^*Correspondance to: Nikolaos Margetis 

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Abstract:

Colorectal cancer, one of the most common cancers, displays disproportionally high mortality, taking into consideration the enormous amount of data collected over the recent decades and the broad use of preventive colonoscopy worldwide. MicroRNAs, small, non coding RNA molecules, regulate many critical steps of the entire stages of colorectal tumorigenesis process and shed light to the in depth comprehension of the complex genetic environment that governs the process. Let-7 is the largest microRNA family studied and consists of ten mature members, which exhibit redundancy in colorectum. Its main role is to promote differentiation and depress stemness, both in normal and neoplastic colon. It represses or abrogates translation of other genes, by complementary binding to their mRNAs. It is mostly considered a tumor-suppressor, as it targets mainly oncogenes; among them K-ras is the dominant. Let-7 establishes feedback loops with the majority of its targets. Its expression levels increase over fetus development, are higher on the top vs the bottom of the colonic crypt and are downregulated, as normal colorectal epithelium progress to neoplasia. Although let7’s tumor-suppressive effect is dependent on the primitive or advanced stage of colorectal neoplasia, colorectal cancer tissues’ let-7 levels are proportionate to cancer stage. High let-7 levels may prove a favorable prognostic and predictive biomarker. In case scientists overcome multiple limitations, the administration of mature let-7 inside colorectal cancer tissues (directly, delivering synthetic let-7 or indirectly, using a viral vector), may improve future management of CRC, since underexpressed let-7 levels favor every single stage of colonic oncogenic transformation.

Keywords:

Let-7; K-ras mutation; LCS6; Biomarker; Colorectal cancer

Cite the Article:

Margetis N, Kotsinas A, Mariolis- Sapsakos T. The Promising Role of Let-7 Microrna in Colorectal Cancer: Practical Points for Clinicians. Clin Oncol. 2018; 3: 1392.