Melanoma is a highly malignant tumor that is common in the skin. In recent years, with the obvious increase in the incidence rate, it has gradually become a common malignant tumor. It is rapid in progress, extremely easy to metastasize, and has a poor clinical prognosis, which is a serious hazard to human health. MicroRNAs are a class of non-coding small-molecule RNAs (18-25 nt) that specifically bind to target mRNA, degrade mRNA or inhibit protein translation, thereby regulating gene expression at the post-transcriptional level and participating in the regulation of biological complex life processes. Researchers at Rockefeller University conducted a systematic study of the mechanisms by which miRNAs regulate melanoma development*, revealing an important mechanism by which multiple miRNA interactions mediate melanoma metastasis. The results were published in the November issue of Cell.

First, the researchers used a chip to perform a comprehensive analysis of miRNA expression profiles in in vitro cultured tumor cell lines (served by Lianchuan Biotechnology) and screened for three specifically expressed miRNAs (miR-1908, miR-199a-5p). , miR-199a-3p) as a follow-up study object. Subsequently, studies confirmed that miR-1908, miR-199a-5p and miR-199a-3p are promoters of metastatic invasion, angiogenesis and proliferation of melanoma. A common target for these miRNAs is the metabolic protein Apolipoprotein E (ApoE) and the heat shock transcription factor DNAJA4, which form a network of miRNA interactions to maximize silencing of ApoE signaling. ApoE secreted by tumor cells inhibits invasion and transfer of endothelial cells, while DNAJA4 promotes ApoE expression. The expression of these three miRNAs and ApoE is closely related to the process of human cancer cell metastasis. Further studies have found that miRNAs have both intracellular and extracellular effects in cancer, revealing a synergistic mechanism of metastasis-associated miRNA networks in cancer cells. Finally, the study confirmed that ApoE is a factor that targets anti-angiogenesis and metastasis, and found that multiple miRNAs have the potential to synergistically combine to treat melanoma.

This study shows that through the study of miRNA and its target genes, it can continuously broaden the field of tumor research and find miRNAs with specific expression, which provides a basis for the early diagnosis and treatment of melanoma.

* Pencheva N, Tran H, Buss C, Huh D, Drobnjak M, Busam K, Tavazoie SF. (2012) Convergent Multi-miRNA Targeting of ApoE Drives LRP1/LRP8-Dependent Melanoma Metastasis and Angiogenesis. Cell [Epub ahead of print] [ abstract ]

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