mir-129 microRNA precursor family
mir-129 microRNA precursor family | |
---|---|
SO | SO:0001244 |
PDB structures | PDBe |
The miR-129 microRNA precursor is a small
Expression Patterns
miR-129 seems to have a tissue specific expression pattern localised to the brain in normal humans. This finding was identified initially by microarray experimentation with mouse tissue (and more specifically to the cerebellum)[1] which was subsequently validated by the expression profiling in human tissue. However, expression in normal brain tissue was found to be relatively low and different profiling experimentation methodologies produced differing results. These differences and the low levels of detection may be attributed to the size and complexity of the human brain and the fact that specific regions of the brain were not individually tested.[6]
Targets of miR-129
Cdk6
As with many other microRNAs, the expression profile of miR-129 changes with the onset of cancer. In many different tumour cell lines, such as
SOX4
SOX4, SRY-related HMG box 4 gene – an oncogene that is known to be deregulated in a number of cancers, is another target of miR-129 in which the aberrant regulation of miR-129 contributes to the proliferation of cancer cell lines. SOX4 is involved in the mediation of transcription response to Wnt signalling. In endometrial cancers and gastric cancers, there has been a clear link established between the epigenetic repression, or loss, of miR-129 and the over-expression of SOX4. In experiments where miR-129 levels were returned to normal in cancer cells, SOX4 expression was down regulated. Further, it has been suggested that promoter hypermethylation of miR-129-2 is the main contributor of SOX4 over expression in some types of cancer.[8][9]
GALNT1
GALNT1, N-acetylgalactosaminyltransferase 1 – involved in TGF-β signalling, is another target of miR-129 that was identified by luciferase assay. It was observed that when cancer cells were subjected to transfection with the precursor of miR-129, GALNT1 was subsequently down regulated by the direct targeting of miR-129. The SOX4 target observation was also validated in this study. These results correlate with the notion that high levels of miR-129 and low SOX4 and GALNT1 levels correlate to cancer cell progression.[10]
APC and Rab11
EIF2C3 and CAMTA1
miR-129 may also play a role in hematopoietic stem cell development. It has been shown that miR-129 may participate in a stem cell developmental network with
Clinical Relevance of miR-129
Biomarkers for Diagnostics
MicroRNAs have given cancer researchers a new perspective to understand and combat cancer. This is due to them being produced in a tissue-specific manner and their roles in many aspects of cellular process, such as proliferation and apoptosis. The vast amount of experimental data has enabled the specific microRNA signatures and profiles to be recognised and thus used as potential biomarkers in cancer diagnosis, therapy prediction and prognosis.
miR-129 has been identified as a potential candidate for development into a diagnostic biomarker. This is because of its integral role it plays in the proliferation of cells and its many recognisable, statistically significant and independent interactions with its targets as observed by the expression profiles in the study carried out by Ogawa et al..[11]
References
Further reading
- Lagos-Quintana, M; Rauhut R; Meyer J; Borkhardt A; Tuschl T (2003). "New microRNAs from mouse and human". RNA. 9 (2): 175–179. PMID 12554859.
- Wu J, Qian J, Li C, et al. (May 2010). "miR-129 regulates cell proliferation by downregulating Cdk6 expression". Cell Cycle. 9 (9): 1809–18. PMID 20404570.
- Dyrskjøt L, Ostenfeld MS, Bramsen JB, et al. (June 2009). "Genomic profiling of microRNAs in bladder cancer: miR-129 is associated with poor outcome and promotes cell death in vitro". Cancer Res. 69 (11): 4851–60. PMID 19487295.
- Shen R, Pan S, Qi S, Lin X, Cheng S (April 2010). "Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 in gastric cancer". Biochem. Biophys. Res. Commun. 394 (4): 1047–52. PMID 20331975.
- Huang YW, Liu JC, Deatherage DE, et al. (December 2009). "Epigenetic Repression of microRNA-129-2 Leads to Overexpression of SOX4 Oncogene in Endometrial Cancer". Cancer Res. 69 (23): 9038–46. PMID 19887623.
- Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ (2006). "miRBase: microRNA sequences, targets and gene nomenclature". Nucleic Acids Res. 34 (Database issue): D140–4. PMID 16381832.
- Lim LP, Glasner ME, Yekta S, Burge CB, Bartel DP (2003). "Vertebrate microRNA genes". Science. 299 (5612): 1540. S2CID 37750545.