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Tumorigenicity

Mutations were identified in 5 of 42 tested miRNA genes in patients with chronic lymphocytic leukemia (CLL), but not in the normal healthy controls. More specifically, mutation of 7 bp downstream from pre-miR15a~16-1 genomic DNA in germline, inhibited processing. A more common form of point mutations is the single nucleotide polymorphism (SNP) which alters the miRNA processing and in some cases the miRNA functions as well. It has been shown that 315 SNPs were associated with 265 human miRNA genes and only 12 of these SNPs were found in miRNA precursor sequences, and one SNP was located in the miR125a seed sequence. Some SNPs could confer the differences in the Droshamediated processing such as miR125a precursor SNPs, miR-146a, miR- 502, miR-510, miR-890, and miR-892b, while differences were observed in the Dicer-conferred processing in some other SNPs such as miR-196a G/T SNPs as well. However, mutations including SNPs are passive consequences of the mutations occurred in the miRNA genes. Therefore, it is not an active/auto miRNA processing regulation mechanism but rather pathologically associated with some human diseases. For example, miR-125a SNP is highly associated with breast cancer tumorigenesis. Thus, SNPs could serve as pathological markers clinically. Yujing Li, Regulation of Mirna Pathway and Roles of Micrornas in Tumorigenesis and Metastasis
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Last date updated on June, 2014

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