Microrna-124 targets flotillin-1 to regulate proliferation and migration in breast cancer

Abstract

BackgroundMicroRNAs (miRNAs) have been documented as playing important roles in cancer development. In this study, we investigated the role of miR-124 in breast cancer and clarified the regulation of flotillin-1 (FLOT1) by miR-124.MethodsThe expression levels of miR-124 were examined in breast cancer cell lines and patient specimens using quantitative reverse transcription-PCR. The clinicopathological significance of the resultant data was later analyzed. Next, we explored the function of miR-124 to determine its potential roles on cancer cell growth and migration in vitro. A luciferase reporter assay was conducted to confirm the target gene of miR-124, and the results were validated in cell lines and patient specimens.ResultsWe found that miR-124 expression was significantly downregulated in breast cancer cell lines and patient specimen compared with normal cell lines and paired adjacent normal tissues (P < 0.0001), respectively. MiR-124 was also associated with tumor node metastasis (TNM) stage (P = 0.0007) and lymph node metastasis (P = 0.0004). In breast cancer cell lines, the ectopic expression of miR-124 inhibited cell growth and migration in vitro. Moreover, we identified the FLOT1 gene as a novel direct target of miR-124, and miR-124 ectopic expression significantly inhibited FLOT1. Luciferase assays confirmed that miR-124 could directly bind to the 3′ untranslated region of FLOT1 and suppress translation. Moreover, FLOT1 was widely upregulated, and inversely correlated with miR-124 in breast cancer tissues. Consistent with the effect of miR-124, the knockdown of FLOT1 significantly inhibited breast cancer cell growth and migration. We also observed that the rescue expression of FLOT1 partially restored the effects of miR-124.ConclusionsOur study demonstrated that miR-124 might be a tumor suppressor in breast cancer via the regulation of FLOT1. This microRNA could serve as a potential diagnostic marker and therapeutic target for breast cancer.

Role of miR-124 and miR-141 in the regulation of vascular reactivity and the relationship to RhoA and Rac1 after hemorrhage and hypoxia

“…Alteration of the expressions of miR-124 and miR-141 with their overexpressed plasmids and antisenses abolished the damage to hypoxia-induced vascular contractile response. This finding provides a new basis on which to treat hypoxia or shock-induced vascular hyporeactivity, the key complication of many critical illnesses such severe trauma, shock, sepsis, multiple organ dysfunction syndrome, and others (11,12). Nevertheless, whether other miRNAs that changed after hypoxia are involved in the regulation of hypoxia-induced vascular contractile dysfunction needs further investigation.…”

MicroRNA-124 inhibits cell proliferation and migration by regulating SNAI2 in breast cancer

“…It has also been reported to function as an important regulator of many human cancers (43,44). In particular, recent studies have indicated that miR-124 targets specific genes to regulate proliferation and migration in breast cancer (45)(46)(47).…”

Flotillins in intercellular adhesion – from cellular physiology to human diseases

“…Moreover, the genomic region containing the flotillin 2 gene is amplified in breast cancer tumors (Berger et al, 2013). Flotillin upregulation is detected in several types of cancers and it is associated with poor patient survival prognosis and high risk of metastasis formation (Doherty et al, 2006;Hazarika et al, 2004;Li et al, 2013;Pust et al, 2013;Rickman et al, 2008;Wang et al, 2013;Zhang et al, 2013;Zhu et al, 2013). In vivo analysis of the role of flotillins during tumorigenesis using a transgenic mouse model of breast cancer has shown that flotillin 2 is not involved in primary tumor formation, but is an important regulator of mammary-tumorderived lung metastasis (Berger et al, 2013).…”