The repressive effect of miR-148a on Wnt/β-catenin signaling involved in Glabridin-induced anti-angiogenesis in human breast cancer cells

Abstract

BackgroundGlabridin (GLA), a major component extracted from licorice root, has anti-inflammatory and antioxidant activities, but few studies report its mechanism of inhibition of angiogenesis. This study was an extension of our previous work, which demonstrated that GLA suppressed angiogenesis in human breast cancer (MDA-MB-231 and Hs-578T) cells. Breast cancer is one of the most common malignant diseases in females worldwide, and the major cause of mortality is metastasis that is primarily attributed to angiogenesis. Thus, anti-angiogenesis has become a strategy for the treatment of breast cancer.MethodsCell viability of different concentration treatment groups were detected by Cell Counting Kit-8 assay. The expression of several related genes in the Wnt1 signaling pathway in MDA-MB-231 and Hs-578T cells treated with GLA were measured at both the transcription and translation levels using quantitative real-time PCR analyses and western blotting. Immunofluorescence assay analyzed the nuclear translocation of β-catenin. The microRNA-inhibitor was used to knockdown microRNA-148a (miR-148a) expression. Angiogenic potentials of breast cancer cells were analyzed by enzyme-linked immunosorbent assay (ELISA) and tube formation in vitro.ResultsGLA attenuated angiogenesis by the suppression of miR-148a-mediated Wnt/β-catenin signaling pathway in two human breast cancer cell lines (MDA-MB-231 and Hs-578T). GLA also upregulated the expression of miR-148a in a dose-dependent manner, miR-148a, which could directly target Wnt-3′-untranslated regions (UTRs), and decreased the expression of Wnt1, leading to β-catenin accumulation in the membranes from the cytoplasm and nucleus. Downregulation of miR-148a contributed to the reduction of GLA-induced suppression of the Wnt/β-catenin signaling pathway, the angiogenesis and vascular endothelial grow factor (VEGF) secretion.ConclusionsOur study identified a molecular mechanism of the GLA inhibition of angiogenesis through the Wnt/β-catenin signaling pathway via miR-148a, suggesting that GLA could serve as an adjuvant chemotherapeutic agent for breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3298-1) contains supplementary material, which is available to authorized users.

MiR‐873 inhibition enhances gefitinib resistance in non‐small cell lung cancer cells by targeting glioma‐associated oncogene homolog 1

“…During angiogenesis, tumor growth changes from slow to rapid; angiogenesis is the key step to facilitate this transformation. Inhibition of angiogenesis can obviously control tumor growth and metastasis . In this study, we found that miR‐873 suppression conspicuously enhanced the viability and growth of PC9 cells treated with gefitinib.…”

“…Inhibition of angiogenesis can obviously control tumor growth and metastasis. [45][46][47][48][49] In this study, we found that miR-873 suppression conspicuously enhanced the viability and growth of PC9 cells treated with gefitinib. Moreover, the inhibition of miR-873 increased angiogenesis.…”

Glabridin induces apoptosis and cell cycle arrest in oral cancer cells through the JNK1/2 signaling pathway

“…Glabridin has been associated with numerous biological properties; it has antioxidant, anti‐inflammatory, antiatherosclerotic, cardiovascular protective, energy metabolism regulating, immunomodulatory, estrogenic, neuroprotective, antiosteoporotic, antinephritic, antibacterial, antifungal, antiobesity, radical scavenging, and skin‐whitening activities . Studies have indicated that glabridin has antitumor effects, including antiproliferation effects in liver and breast cancers; antimetastatic effects in liver, breast, and lung cancers; antiangiogenetic effects in breast and lung cancers; inhibitory effects on the cancer stem cell–like properties in breast and lung cancers; and antiapoptotic effects in leukemia and liver cancers. However, the effects of glabridin on human oral cancer apoptosis have not been evaluated.…”

Casticin inhibits invasion and proliferation via downregulation of β‐catenin and reversion of EMT in oral squamous cell carcinoma

“…β‐catenin, as one of the main component of the Wnt/β‐catenin signaling pathway, mainly participates in mediating cell adhesion. Wnt/β‐catenin plays important roles in EMT . It has been reported that enrichment of β‐catenin in nuclear could cause EMT in cancer, and the lower expression of E‐cadherin can lead to accumulation of β‐catenin, and then, β‐catenin in the cytoplasm translocated to the cell nucleus to induce the transcription of EMT related genes .…”

“…Wnt pathway is an evolutionarily conserved signaling pathway which regulates cell differentiation, cell fate determination, and cell migration during embryogenesis . Meanwhile, many studies show that Wnt signaling regulates cell motility, migration, differentiation, proliferation, and survival in various types of cancer, including OSCC . In the canonical Wnt signaling pathway, activation of Wnt signaling could lead to nuclear accumulation of β‐catenin, which could cause EMT program .…”