microRNA 515-2 (MIR515-2)

MicroRNA 515-2 is a regulatory, non-coding RNA of the microRNA family involved in post-transcriptional gene silencing and regulation of mRNA translation and stability. It is generated as part of a hairpin-structured precursor (pri-miR-515), which is processed by the Drosha enzyme to form the mature miRNA[1][2]. miR-515 regulates gene expression by binding to target mRNAs, such as sphingosine kinase 1 (SK1), resulting in decreased SK1 protein levels and lowering of the signaling molecule sphingosine 1-phosphate (S1P). Inhibition of miR-515, via small molecules like Targaprimir-515 or antisense oligonucleotides, has been shown to upregulate SK1 and S1P, promote proliferation and migration of cancer cells, and modulate levels of proteins such as HER2 (ERBB2) and frizzled class 5 receptor (FZD5), which are relevant for cancer therapy sensitivity[1]. miR-515 has become a target for therapeutic intervention, especially in cancers lacking HER2 expression, by sensitizing them to anti-HER2 treatments[1]. The broad regulatory role of microRNAs poses safety and off-target risks for such therapies.

Other names

hsa-mir-515-2MIRN515-2miR-515MIR515-2

Small molecule inhibitors interfere with biogenesis of miR-515 by binding to precursor regions and preventing processing (inhibition at the Drosha site)[1] Antisense oligonucleotides induce degradation of mature miR-515 through complementary binding[1] Sensitization of cancer cells to anti-HER2 therapies through upregulation of HER2 mediated by de-repression of downstream targets (e.g., SK1/S1P pathway)[1]