PT  - JOURNAL ARTICLE
AU  - Sharan Malagobadan
AU  - Chai San Ho
AU  - Noor Hasima Nagoor
TI  - MicroRNA-6744-5p promotes anoikis in breast cancer and directly targets NAT1 enzyme
AID  - 10.20892/j.issn.2095-3941.2019.0010
DP  - 2020 Feb 15
TA  - Cancer Biology and Medicine
PG  - 101--111
VI  - 17
IP  - 1
4099  - http://www.cancerbiomed.org/content/17/1/101.short
4100  - http://www.cancerbiomed.org/content/17/1/101.full
SO  - Cancer Biol Med2020 Feb 15; 17
AB  - 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 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 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.