Mir-31

Functions

mir-31 has been linked to Duchenne muscular dystrophy − a genetic disorder characterised by a lack of the protein dystrophin − as a potential therapeutic target. Duchenne muscular dystrophy is caused by mutations arising in the dystrophin gene, which impair the translation of dystrophin through the formation of premature termination codons.

miR-31 overexpression is more abundant in human Duchenne muscular dystrophy than in healthy controls, with levels remaining high only in Duchenne muscular dystrophy myoblasts. miR-31 levels in healthy controls are instead decreased with the onset of cell differentiation. miR-31 is part of the circuit controlling late muscle differentiation by repression of dystrophin synthesis, and its expression is localised specifically to regenerating myoblasts of dystrophic muscles. miR-31 is believed to repress the expression of dystrophin by antisense binding of the dystrophin mRNA 3′ untranslated region, and in this way it is thought that miR-31 manipulation could aid treatment for Duchenne muscular dystrophy.

Applications

In serous ovarian cancer, miR-31 is frequently deleted and is the most underexpressed microRNA in this cancer type. It has been shown to affect the levels of gene transcription factor p53, responsible for encoding the tumour suppressor protein p53. Cancer cell lines with an inactive p53 pathway show a vulnerability to miR-31 overexpression, whilst there is resistance to overexpression in cell lines with a functional p53 pathway. miR-31 overexpression is associated with a better prognosis in tumours, suggesting that therapeutic delivery of miR-31 may be beneficial in patients with p53-deficient cancers. Conversely, in gastric cancer miR-31 levels have been found to be significantly lower in tumour cells relative to healthy cells, meaning further potential for use as a diagnostic marker. However, high expression levels of miR-31 correlate to shorter survival in patients with malignant pleural mesothelioma, whereas longer survival has been associated with normal/low expression of miR-31 from blood-based samples. Furthermore, in vivo, anti-miR-31 has proved to reduce miR-31-5p overexpression suppressing the esophageal preneoplasia in Zinc deficient rats. This leads to the repression of miR-31-5p target Stk40 by the inhibition of the STK40-NF-κΒ-controlled inflammatory pathway, with resultant decreased cellular proliferation and activated apoptosis. Notably Zn replenishment is able to restore the regulation of miR-31-5p targets leading to a normal esophageal phenotype.{{cite journal |author1=Cristian Taccioli |author2=Michela Garofalo |author3=Hongping Chen |author4=Yubao Jiang |author5=Guidantonio Malagoli Tagliazucchi |author6=Gianpiero Di Leva |author7=Hansjuerg Alder |author8=Paolo Fadda |author9=Justin Middleton |author10=Karl J Smalley |author11=Tommaso Selmi |author12=Srivatsava Naidu |author13=John L Farber |author14=Carlo M Croce |author15=Louise Y Fong | title=Repression of Esophageal Neoplasia and Inflammatory Signaling by Anti-miR-31 Delivery In Vivo. | journal=J Natl Cancer Inst

References

References

1. O'Day, E. (2010). "MicroRNAs and their target gene networks in breast cancer.". Breast Cancer Research.
2. Cacchiarelli, D. (February 2011). "miR-31 modulates dystrophin expression: new implications for Duchenne muscular dystrophy therapy.". EMBO Reports.
3. (2011). "miR-31 modulates dystrophin expression: new implications for Duchenne muscular dystrophy therapy.". EMBO Rep.
4. (1993). "Comparative study of p53 gene and protein alterations in human astrocytic tumors.". J Neuropathol Exp Neurol.
5. (2010). "Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers.". Cancer Res.
6. Zhang, Y. (September 2010). "Down-regulation of miR-31 expression in gastric cancer tissues and its clinical significance.". Medical Oncology (Northwood, London, England).
7. (June 2015). "MicroRNAs in mesothelioma: from tumour suppressors and biomarkers to therapeutic targets". Journal of Thoracic Disease.
8. (2009). "Human natural Treg microRNA signature: role of microRNA-31 and microRNA-21 in FOXP3 expression.". Eur J Immunol.
9. (2011). "Dicer insufficiency and microRNA-155 overexpression in lupus regulatory T cells: an apparent paradox in the setting of an inflammatory milieu.". J Immunol.