MicroRNA miR-30 family regulates non-attachment growth of breast cancer cells

Abstract

BackgroundA subset of breast cancer cells displays increased ability to self-renew and reproduce breast cancer heterogeneity. The characterization of these so-called putative breast tumor-initiating cells (BT-ICs) may open the road for novel therapeutic strategies. As microRNAs (miRNAs) control developmental programs in stem cells, BT-ICs may also rely on specific miRNA profiles for their sustained activity. To explore the notion that miRNAs may have a role in sustaining BT-ICs, we performed a comprehensive profiling of miRNA expression in a model of putative BT-ICs enriched by non-attachment growth conditions.ResultsWe found breast cancer cells grown under non-attachment conditions display a unique pattern of miRNA expression, highlighted by a marked low expression of miR-30 family members relative to parental cells. We further show that miR-30a regulates non-attachment growth. A target screening revealed that miR-30 family redundantly modulates the expression of apoptosis and proliferation-related genes. At least one of these targets, the anti-apoptotic protein AVEN, was able to partially revert the effect of miR-30a overexpression. Finally, overexpression of miR-30a in vivo was associated with reduced breast tumor progression.ConclusionsmiR30-family regulates the growth of breast cancer cells in non-attachment conditions. This is the first analysis of target prediction in a whole family of microRNAs potentially involved in survival of putative BT-ICs.

Evolution of themiR199-214cluster and vertebrate skeletal development

“…Redundancy of miRs within a family or a cluster has already been suggested in several cases such as the miR17-92 cluster during development 65 and miR30 family members in breast cancer. 66 Furthermore, the generation of numerous miR gene deletion mutations in Caenorhabditis elegans led to the conclusion that most miRs are not individually essential for development or viability, thus supporting the hypothesis that many miRs function redundantly. 67 Because miR199-1a and miR199-2 show developmental expression patterns that differ from other miR199 genes, sub-functionalization of regulatory features or the evolution of novel regulatory features (neofunctionalization) may have occurred in this case.…”

Down-Regulation of MiR-30c Promotes the Invasion of Non-Small Cell Lung Cancer by Targeting MTA1

“…Meanwhile, miR-30c inhibited expression of SERPINE 1 in human endothelial cells [18]. In human, the miR-30 family (miR-30a/b/c/d/e/f) was also reported in various cancers, such as breast [19], retinal pigment epithelial cells [20], glioma [21], and osteoblast [22]. However, recent literature indicated that aberrant expression level of miR-30c induced tumorigenesis and gefitinib resistance in lung cancer, while miR-30c was altered by EGFR and MET receptor tyrosine kinase [23].…”

Absent expression of miR‑30a promotes the growth of lung cancer cells by targeting MEF2D

“…Several studies have revealed that miR-30d and miR-30a are antimetastatic factors in tumors (5,6), and interfere with the epithelial-mesenchymal transition (EMT) (7). Certain miR-30 family members have been identified to abrogate chemoresistance and promote cancer cell apoptosis (7)(8)(9)(10)(11)(12). In a previous study on lung cancer, Chan et al established the potential role of the miR-30 family in the modulation of the phosphoinositide 3-kinase-seven in absentia homolog 2 interaction in non-small cell lung cancer (NSCLC) (13).…”