The miR-17 family comprise miRs 17 and 20a in the miR-17 ~ 92 cluster, 106a and 20b in the miR-106a ~ 363 cluster and 106b and 93 in the miR-106b ~ 25 cluster 8. Over expression of the miR-17 ~ 92 cluster has been observed in multiple tumor types including hematological malignancies (B-cell lymphomas) and solid tumors (breast, lung, CRC, pancreas and prostate) 11, 12. The cluster was first discovered in 2005, when it was found to act with c-MYC to promote tumorigenesis in B-cell lymphomas 11. In normal development it is involved in lung and heart maturation and hematopoiesis, where it promotes cell proliferation and survival 10. miR-17 ~ 92 is predominantly related to cell cycle regulation. The polycistronic structure of miR cluster genes differs from most protein coding genes, as multiple miRs can be produced within a single pri-miR transcript. Collectively, these 15 mature miRs are grouped into four families, namely the miR-17, miR-18, miR-19 and miR-92 8. There are two miR-17 ~ 92 cluster paralogs in mammals: miR-106b ~ 25 located on chromosome 7 and miR-106a ~ 363 located on the X-chromosome, comprising an additional 6 and 3 mature miRs. The miR-17 ~ 92 cluster, located at chromosomal locus 13q31.3, comprises six tandem stem-loop hairpin structures that yield six mature miRs (miR-17, miR-18a, miR-19a, miR-19b, miR-20a and miR-92a) 7. In cancer, miRs act as both oncogenes and tumor suppressors 6. miRs influence diverse biological mechanisms including apoptosis, growth, differentiation and proliferation 5. An estimated 30% of human genes are regulated by miRs 4. They regulate gene expression at the post-transcriptional level. MicroRNAs (miRs or miRNAs) are short, non-coding RNAs, approximately 22 nucleotides long. To further tailor the treatment of these patients, the development of novel prognostic and predictive biomarkers is important 2, 3. Despite improved diagnostics and treatment, and decreasing incidence, the mortality of colon cancer remains high. In 2020, it is estimated that 1 150 000 patients experienced a de novo colon cancer and that 575 000 succumbed to their disease. In conclusion, in stage I-III colon cancer, high expression of both miR-17-5p and miR-20a-5p are independent predictors of favorable prognosis.Ĭolon cancer is the 4th most and 5th most common cause of cancer and cancer related deaths, respectively 1. In cell lines, over expression of both miRs resulted in mitigated migration without any significant effect on viability or invasion. Cell line experiments, using HT-29 and CACO-2, were performed to assess the effect of miR-17-5p and miR-20a-5p over expression on viability, invasion and migration. miR-17-5p and miR-20a-5p expression was evaluated by in situ hybridization and analyzed using digital pathology.
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Tumor tissue from 452 stage I-III colon cancer patients was retrospectively collected and tissue microarrays constructed. The aim of this study was to explore the prognostic impact of miR-17-5p and miR-20a-5p in colon cancer.
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In many types of cancer, microRNAs (miRs) are aberrantly expressed.