MicroRNA-195 inhibits proliferation, invasion and metastasis in breast cancer cells by targeting FASN, HMGCR, ACACA and CYP27B1.

Abstract

De novo lipogenesis, a hallmark for cancers is required for cellular transformation. Further it is believed that resistance to apoptosis and epithelial-to-mesenchymal-transition(EMT) facilitates metastasis via over-expression of anti-apoptotic Bcl-2. Previously we demonstrated that hsa-miR-195 targets BCL2, induces apoptosis and augmented the effect of etoposide in breast cancer cells. However, the mechanism behind its function remains elusive. Herein gene expression profiling was done in presence/absence of hsa-miR-195 in Breast cancer cells. IPA revealed mitochondrial dysfunction, fatty acid metabolism and xenobiotic metabolism signalling among the top processes being affected. For the first time we herein identified ACACA, FASN (the key enzymes of de novo fatty acid synthesis), HMGCR (the key enzyme of de novo cholesterol synthesis) and CYP27B1 as direct targets of hsa-miR-195. We further showed that ectopic expression of hsa-miR-195 in MCF-7 and MDA-MB-231 cells not only altered cellular cholesterol and triglyceride levels significantly but also resulted in reduced proliferation, invasion and migration. We further demonstrated that over expression of hsa-miR-195 decreased the Mesenchymal markers expression and enhanced Epithelial markers. In conclusion we say that hsa-miR-195 targets the genes of de novo lipogenesis, inhibits cell proliferation, migration, and invasion which potentially opens new avenues for the treatment of breast cancer.

• Authors: Richa Singh, Vikas Yadav, Sachin Kumar, Neeru Saini
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 17454 (Dec 03 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26632252 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN195 microRNA, human
• MicroRNAs
• HMGCR protein, human
• Hydroxymethylglutaryl CoA Reductases
• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
• CYP27B1 protein, human
• FASN protein, human
• Fatty Acid Synthase, Type I
• ACACA protein, human
• Acetyl-CoA Carboxylase

Topics

• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (genetics, metabolism)
• Acetyl-CoA Carboxylase (genetics, metabolism)
• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation
• Epithelial-Mesenchymal Transition (genetics)
• Fatty Acid Synthase, Type I (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Hydroxymethylglutaryl CoA Reductases (genetics, metabolism)
• Lipid Metabolism (genetics)
• MicroRNAs (genetics, metabolism)
• Mitochondria (genetics, metabolism)