MiR-204-5p overexpression abrogates Dacarbazine-induced senescence in melanoma cells in vivo MiR-204-5p abrogates senescence.

MiR-204-5p overexpression abrogates Dacarbazine-induced senescence in melanoma cells in vivo MiR-204-5p abrogates senescence.

Publication date: Feb 01, 2025

Cancer cell drug resistance hinders significantly therapeutic modalities in oncology. Dacarbazine is chemotherapeutic agent traditionally used for melanoma treatment although it’s effectiveness insufficient. In the present study we performed NGS-based transcriptomic profiling of B16 melanoma tumors after Dacarbazine treatment in vivo. Whole transcriptome sequencing revealed 34 differentially expressed genes most of them associated with drug resistance and apoptosis evading. In accordance to bionformatic analysis, 6 signaling cascades: “D-Amino acid metabolism”, “NF-kappa B signaling pathway”, “Phosphatidylinositol signaling system”, “P53 signaling pathway”, “IL-17 signaling pathway” and “Bile secretion” were enriched by differentially expressed genes. Next we provided a combined treatment by Dacarbazine and miR-204-5p mimic as miR-204-5p was considered previously implicated in cancer drug resistance. This approach lead to an increase of miR-204-5p expression in B16 melanoma cells in vivo that was accompanied by subsequent decrease in the expression of miR-204-5p target genes – BCL2 and SIRT1 in the primary tumors. MiR-204-5p overexpression with Dacarbazine application resulted in increased the weight, and volume of primary tumors and diminished the proportion of β-Galactosidase expression in melanoma B16-bearing mice. Taking together, our study revealed that although miR-204-5p showed antiproliferative capacities in vitro, it’s mimic in combination with Dacarbazine is able to potentiate tumor growth triggering probably a switch from senescent to proliferative phenotype of malignant cells.

Concepts Keywords
5p Dacarbazine
Apoptosis Drug resistance
Bionformatic DTIC
Mice Melanoma
Phosphatidylinositol miR-204-5p
NGS
Senescence
Transcriptome

Semantics

Type Source Name
drug DRUGBANK Dacarbazine
disease MESH melanoma
pathway KEGG Melanoma
disease MESH Cancer
disease MESH B16 melanoma
pathway REACTOME Apoptosis
pathway KEGG D-Amino acid metabolism
pathway KEGG NF-kappa B signaling pathway
pathway KEGG Phosphatidylinositol signaling system
pathway KEGG p53 signaling pathway
pathway KEGG IL-17 signaling pathway
pathway KEGG Bile secretion

Original Article

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