MiR‐577 suppresses epithelial‐mesenchymal transition and metastasis of breast cancer by targeting Rab25

Abstract

BackgroundMicroRNAs can act as both tumor suppressor genes and oncogenes and participate in cell proliferation, metastasis, and apoptosis. Low levels of miR‐577 are found in several cancers, for example, thyroid carcinoma, glioblastoma, and hepatocellular carcinoma. The aim of this study was to investigate the effect of miR‐577 on breast cancer (BC).MethodsThe relative level of miR‐577 in 120 BC tissues and cells was detected by real‐time PCR. MDA‐MB‐231 cells with upregulated miR‐577 and MCF‐7 cells with downregulated miR‐577 were established. Transwell invasion assays were used to examine the invasiveness of cells. Epithelial‐mesenchymal transition (EMT) markers were evaluated by immunofluorescence and Western blot. Targeted combinations of miR‐577 and Rab25 were analyzed by luciferase assays. Xenograft models were used to examine the effect of miR‐577 on BC metastasis.Results MiR‐577 expression was significantly suppressed in BC tissues. Tumor size, tumor stage, and lymphatic metastasis were attributed to miR‐577 expression. Moreover, miR‐577 overexpression strongly inhibited the invasiveness and EMT of BC cells in vitro. MiR‐577 directly regulated Rab25 in BC. Rab25 upregulation by miR‐577 decreased the levels of E‐cadherin and increased the levels of Vimentin. Notably, Rab25 knockdown inhibited BC invasion; however, an increase in Rab25 counteracted the invasive effect of miR‐577 in BC.ConclusionResults indicated that miR‐577 suppressed EMT by inhibiting Rab25 expression in BC. MiR‐577 and Rab25 are considered potential targets of BC treatment.

miR-577 suppressed the metastasis, EMT and viability via NF-κB pathway by targeting CXCL5 through in hepatocellular carcinoma

“…miR-577 acted as tumor suppressor to inhibit cell proliferation, migration and invasion in papillary thyroid carcinoma [26]. miR-577 suppressed metastasis and EMT of breast cancer [27]. Consistent with all the findings, we proposed that miR-577 was downregulated and miR-577 inhibited cell viability and invasion in HCC.…”

microRNA‑577 inhibits cell proliferation and invasion in non‑small cell lung cancer by directly targeting homeobox A1

“…miR-577 expression has been examined in several types of human cancer. For example, miR-577 expression is downregulated in breast cancer, and this downregulation is significantly correlated with tumor size, stage and lymphatic metastasis (21). In addition, miR-577 expression is reduced in hepatocellular carcinoma tissues and cell lines, and low miR-577 expression is associated with tumor size and metastasis (22).…”

“…miR-577 serves as a tumor suppressor in human cancer types. For instance, miR-577 overexpression inhibits epithelial-mesenchymal transition and invasion in breast cancer cells (21). In hepatocellular carcinoma, the upregulation of miR-577 suppresses cell proliferation, promotes cell apoptosis and induces cell cycle arrest at the G 0 /G 1 phase (22).…”

“…Various genes have been demonstrated to be the direct targets of miR-577, including Ras-related protein Rab-25 in breast cancer (21), β-catenin in hepatocellular carcinoma (22), heat shock protein27 in colorectal cancer (23), sphingosine kinase 2 in papillary thyroid carcinoma (24), E2F transcrip- (24), E2F transcrip- (24), E2F transcription factor 3 in gastric cancer (31) and testis specific 10 in esophageal squamous cell carcinoma (32). In the present study, HOXA1, mapped to the short arm of chromosome 7 at band 15.2 (7p15.2), was validated as a direct target gene of miR-577 in NSCLC cells.…”

“…Hence, miRNAs have potential as targets in NSCLC diagnosis, treatment and prognosis. miR-577 has been reported to be abnormally expressed in several tumor types (21)(22)(23)(24). However, the expression pattern, roles and underlying mechanisms of miR-577 in NSCLC have not been clarified.…”