MICRORNA-6744-5P PROMOTES ANOIKIS IN BREAST CANCER AND DIRECTLY TARGETS NAT1 ENZYME

MicroRNA-6744-5p promotes anoikis in breast cancer and directly targets NAT1 enzyme

MicroRNA-6744-5p promotes anoikis in breast cancer and directly targets NAT1 enzyme

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Objective: Anoikis is apoptosis that is induced when cells detach from the extracellular matrix and neighboring cells.As anoikis serves as a regulatory barrier, cancer cells often acquire resistance towards anoikis during tumorigenesis to become metastatic.MicroRNAs (miRNAs) are short strand RNA molecules L-Ornithine that regulate genes post-transcriptionally by binding to mRNAs and reducing the expression of its target genes.This study aimed to elucidate the role of a novel miRNA, miR-6744-5p, in regulating anoikis in breast cancer and identify its target gene.

Methods: An anoikis resistant variant of the luminal A type breast cancer MCF-7 cell line (MCF-7-AR) was generated by selecting and amplifying surviving cells after repeated exposure to growth in suspension.MiRNA microarray analysis identified a list of dysregulated miRNAs from which miR-6744-5p was chosen for overexpression and knockdown studies in MCF-7.Additionally, the miRNA HAIR HYDRATION CARE was also overexpressed in a triple-negative breast cancer cell line, MDA-MB-231, to evaluate its ability to impair the metastatic potential of breast cancer cells.Results: This study showed that overexpression and knockdown of miR-6744-5p in MCF-7 increased and decreased anoikis sensitivity, respectively.

Similarly, overexpression of miR-6744-5p in MDA-MB-231 increased anoikis and also decreased tumor cell invasion in vitro and in vivo.Furthermore, NAT1 enzyme was identified and validated as the direct target of miR-6744-5p.Conclusions: This study has proven the ability of miR-6744-5p to increase anoikis sensitivity in both luminal A and triple negative breast cancer cell lines, highlighting its therapeutic potential in treating breast cancer.

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