The repressive effect of miR-520a on NF-κB/IL-6/STAT-3 signal involved in the glabridin-induced anti-angiogenesis in human breast cancer cells

Abstract

The formation of blood vessels plays a vital role in the growth of tumors. Breast cancer is a type of vascular dependent tumor, and angiogenesis plays an important role in its invasion and metastasis. Thus, the continued search for new mechanisms that inhibit the formation of blood vessels is becoming a strategy for the treatment of breast cancer. Glabridin (GLA) is a novel anti-tumor agent that inhibits oxidization, inflammation, and proliferation in human cancer cells. However, the functions of GLA in the regulation of angiogenesis in breast cancer and its underlying molecular mechanisms remain largely uninvestigated.In our present study, GLA attenuated the angiogenic ability by the microRNA-520a (miR-520a)-mediated inhibition of the NF-kB/IL-6/STAT-3 signal pathway in MDA-MB-231 and Hs-578T cells. Briefly, in these cells, GLA up-regulated the expression of miR-520a in a time-dependent manner; miR-520a, which targeted the NF-kB/RelA-3 0 UTR, decreased the expression/function of NF-kB, leading to the inactivation of IL-6/STAT-3 signaling; the knockdown of miR-520a abolished the GLA-induced inhibitions of the NF-kB/IL-6/STAT-3 signal pathway, the VEGF secretion, and the angiogenesis. By understanding the novel mechanism in which GLA inhibits the angiogenic potential in human breast cancer cells, our study would help in the design of future strategies in terms of developing GLA as a potential chemopreventive agent, when used alone or in combination with other current anticancer drugs.

Current state of phenolic and terpenoidal dietary factors and natural products as non-coding RNA/microRNA modulators for improved cancer therapy and prevention

“…Similar results were obtained from breast cancer cells (MDA-MB-231, Hs-578T) treated with glabridin [148] . In addition, glabridin inhibited angiogenesis of breast tumors (MDA-MB-231, Hs-578T) by upregulation of miR-520a [149] . The expression of NF-κB was blocked by upregulated miR-520a in glabridin-treated breast cancer cells associated with inhibition of NF-κB/IL-6/STAT-3 signaling.…”

Botanicals and Their Bioactive Phytochemicals for Women’s Health

“…Isoliquiritigenin inhibited phorbol ester-induced COX-2 expression in MCF-10A cells by modulating the ERK1/2 signaling pathway ( Lau et al, 2010 ). Glabridin was reported to exert chemopreventive effects by attenuating angiogenesis via inhibiting NF-κB/IL-6/signal transducer and activator of transcription 3 signaling pathway in MDA-MB-231 and Hs-578T cells ( Mu et al, 2015 ).…”

MicroRNA-520a suppresses HBV replication in HepG2.2.15 cells by inactivating AKT

“…At the same time-points, intracellular HBV DNA was extracted from virus core particles as described previously. 8 , 9 In brief, the nuclei and cellular debris were removed from HepG2.2.15 cell lysates and then the supernatants were digested with micrococcal nuclease at 37°C for 2 h. Viral DNA was separated and then used in the RT–PCR method described above. 9 …”

“… 8 MiR-520a promoted the antitumour activities of GLA by inhibiting the nuclear factor (NF)-κB/interleukin (IL)-6/signal transducer and activator of transcription (STAT)-3 signalling pathway. 9 In summary, GLA could upregulate the expression of miR-520a, which targets the 3ʹ untranslated region (UTR) of the NF-κB/RELA mRNA, thus inhibiting the production and function of NF-Κb. 9 …”

“… 9 In summary, GLA could upregulate the expression of miR-520a, which targets the 3ʹ untranslated region (UTR) of the NF-κB/RELA mRNA, thus inhibiting the production and function of NF-Κb. 9 …”