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UHRF1 is regulated by miR-9 in colorectal cancer

Study on the regulation of UHRF1 by miR-9 in colorectal cancer, including expression levels, correlation with clinicopathologic features, and therapeutic implications.

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UHRF1 is regulated by miR-9 in colorectal cancer

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  1. UHRF1 is regulated by miR-9 in colorectal cancer Feng Yan Department of Clinical Laboratory, Nanjing Medical University Cancer Hospital, Nanjing, 210009,China Email: yanfeng1895@163.com

  2. SEER Stat Fact Sheets: Colon and Rectum Cancer http://seer.cancer.gov/statfacts/html/stomach.html

  3. Expected Cancer Incidence and Mortality in 2015, China

  4. UHRF1(Ubiquitin-like with PHD and ring finger domains) UHRF1 has been identified as a novel oncogene. known as ICBP90 or Np95,located on the short (p) arm of chromosome 19 at position 13.3 (Gene ID: 29128). in vertebrates, the SRA domain is restricted to the UHRF family. Biochemical Pharmacology 86 (2013)1643–1649

  5. UHRF1 and cancer Biochemical Pharmacology 86 (2013)1643–1649

  6. miR-9 and CRC In CRC, miR-9 serves as a tumor suppressor miR-9 is associated with the development of CRC and could be utilized for CRC molecular targeted therapies

  7. Samples collection Cells: HT29 and HCT116 pairs of CRC tissues: 38cancer tissues and adjacent normal tissues average age of 69 years (ranging from 45 to 85 years)

  8. UHRF1expression in tissues Strong staining was found mainly in nucleus 36.8%(14/38) , positive 23.6%(9/38), strong expression 13.2%(5/38), moderate expression

  9. MiR-9 expression is downregulated in CRC tissues in situ hybridization results miR-9 reduced in CRC tissues U6 snRNA expression levels remained unchanged

  10. the expression levels of miR-9 RT-PCR results significantly lower in the CRC specimens than those in the adjacent non-cancerous specimens

  11. The correlation between the miR-9 expression and clinicopathologic features of CRC

  12. Kaplan–Meier survival analysis low miR-9 expression associated with a poor clinical outcome Multivariate survival analysis：miR-9 expression level and distant metastasis were independent prognostic factors for outcome in patients with CRC.

  13. Establish stable HCT-116 and HT29 cell lines expressing lenti-miR-9 After transfection for 72 h in cells, the expression levels of miR-9 were substantially increased about 57-fold and 45-fold, respectively, compared to pre-miR-control.

  14. cell proliferation assays over expression of miR-9 can significantly inhibit CRC cell proliferation (P < 0.05)

  15. colony formation assay colony formation was significantly reduced in the miR-9 upregulated cells

  16. miR-9 promotes CRC cells apoptosis in vitro After transfection with miR-9 for 72 h, the proportion of apoptotic cells was significantly increased in HCT-116 and HT29

  17. UHRF1 is a direct target of miR-9 the expression of UHRF1 significantly decreased in stable Pre-miR-9-transfection cells, whereas UHRF1 was upregulated after inhibition of miR-9 in both cell lines

  18. the relationship between miR-9 and UHRF1 miR-9 could target 3’UTR region of UHRF1. To validate the prediction, the wild-type or mutation 3’UTRs of UHRF1 was cloned into luciferase reporter vector

  19. the relationship between miR-9 and UHRF1 Dual-Luciferase reporter assay showed that compared to miRNA cont, miR-9 leaded to a significant relative luciferase activity reduction in the wild-type UHRF1 3’UTRplasmid. While the luciferase activity was not reduced in the 3’UTR with mutant binding sites

  20. RT-PCR to analyze the expression of UHRF1 UHRF1 mRNA expression (r=-0.606, p=0.0004) Spearman’s correlated

  21. 1.UHRF1 is regulated by miR-9 in CRC 2.miR-9 was underexpressed in CRC tissues 3. miR-9 was inversely correlated with UHRF1 Summary 4. overexpression of miR-9 could suppress the expression of UHRF1. 5. Cell proliferation was also suppressed in pre-miR-9 transfected cells. 6. restoration of miR-9 expression significantly induced cell apoptosis. 7.more researches on a larger population are needed to confirm these results

  22. UHRF1 is upregulated in CRC. miR-9 could function as a tumor-suppressive miRNA by repressing UHRF1 expression. not only increase our understanding of CRC tumorigenesis, but also allow the development of a novel therapeutic strategy based on upregulation of miR-9. Conclusion

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