MiRNA 3613-5p and MiRNA 3916 rescued the inhibition of cell migration in CNOT2 depleted MDA-MD-231 cells.

Abstract

BackgroundThe CCR4-NOT complex (CNOT) plays an important role in regulating translation repression. Here, silencing of the complex via the transfection of MDA-MB-231 breast cancer cells with CNOT2 Small interfering RNA (siRNA) decreased the mRNA expression of DiGeorge Syndrome Critical Region 8 (DGCR8) and Dicer.MethodsGene expression profiling using an miRNA array was carried out with CNOT2 siRNA treated MDA-MB-231 cells. After transfection with CNOT2 siRNA, qRT-PCR was used to see the level of Dicer and DGCR8. PANTHER pathway analysis was used to see the biological function of microRNAs (miRNAs or miRs).ResultsCNOT2 siRNAs were attenuated the mRNA levels of Dicer and DGCR8. An analysis of miRNAs in CNOT2 silenced MDA-MB-231 cells using miRNA array revealed that 42 miRNAs, including has-miR-7, has-miR-4283, has-miR-10a were significantly upregulated while 47 miRNAs, including has-miR-3916 and has-miR-3613-5p were downregulated following CNOT2 silencing in MDA-MB-231 cells. Also, has-miR-3613-5p and has-miR-3916 rescued the inhibition of migration from CNOT2 short hairpin RNA (shRNA) MDA-MB-231 stable cell lines. PANTHER pathway analysis assigned the miRNAs to multiple processes, including Wnt signaling, angiogenesis, cadherin signaling, inflammation mediated by chemokine and cytokine signaling, integrin signaling, EGF receptor signaling and Huntington’s disease.ConclusionsTogether, our findings provide useful target genes for understanding the molecular mechanisms of CNOT2 in breast cancer.