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THE FEATURES OF miRNA BINDING SITES IN CDS OF ALK mRNA
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| THE FEATURES OF miRNA BINDING SITES IN CDS OF ALK mRNA
Yurikova O.Yu. al-Farabi Kazakh National University oksanayurikova@mail.ru NSCLC - one of the most genetically diverse cancers, which makes it necessary to carry out the therapy considering molecular subtype. About 5% of NSCLCs are caused by a rearrangement in ALK gene. In the vast majority of cases, ALK rearrangements are non-overlapping with other mutations found in NSCLC and require therapy with ALK-targeted inhibitors. Mutation, rearrangements and amplification of ALK gene have been found in a series of tumors including NSCLC anaplastic large cell lymphomas, and neuroblastoma. ALK gene expression can be regulated by miRNAs. Therefore, search of miRNA binding sites in mRNA of ALK gene is essential for better understanding of post-transcriptional regulation of ALK expression and possible use of miRNAs for diagnostics of NSCLC. We predicted miRNA binding sites in mRNA of ALK gene using MirTarget program. miRNA binding sites in protein coding sequence (CDS) of mRNA of ALK gene were detected among 6479 miRNAs. It was identified that region of mRNA of ALK gene between 3387 and 3424 nucleotides is the target for 10 miRNAs: miR-1281, miR-11-29785, miR-13-35476-3p, miR-17-39011-3p, miR-7-20459-3p, miR-9-25099- 3p, miR-6792-3p, miR-1-2802-3p, miR-22-40302-3p, miR-X-48174-3p. This region of mRNA encodes EWAGGGGGGGGA oligopeptide. There are 5 binding sites for miR-1281, 4 for miR-11-29785, 4 for miR- 13-35476-3p, 2 for miR-17-39011-3p, 3 for miR-7-20459-3p, 5 for miR-9-25099-3p and one site for miR- 6792-3p, miR-1-2802-3p, miR-22-40302-3p, miR-X-48174-3p in mRNA of ALK gene. The interaction value of miRNAs with mRNA binding sites of ALK gene is 80% -90% of the maximum value of binding energy of miRNA with a fully complementary nucleotide sequence. This arrangement of binding sites localized within the sequence of 37 nucleotides in mRNA of ALK gene may serve as example of cluster organization of miRNA binding sites in CDS. It is likely that in this case suppression of ALK protein expression depends on level of expression of described miRNAs. Scientific adviser: Atambayeva Sh. A., Candidate of Biological Sciences, Assoc. Prof. жүктеу/скачать 2,79 Mb. Достарыңызбен бөлісу:
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