Snail Promotes Cancer Cell Proliferation via Its Interaction with the BIRC3

Abstract

Snail is implicated in tumour growth and metastasis and is up-regulated in various human tumours. Although the role of Snails in epithelial-mesenchymal transition, which is particularly important in cancer metastasis, is well known, how they regulate tumour growth is poorly described. In this study, the possible molecular mechanisms of Snail in tumour growth were explored. Baculoviral inhibitor of apoptosis protein (IAP) repeat-containing protein 3 (BIRC3), a co-activator of cell proliferation during tumourigenesis, was identified as a Snail-binding protein via a yeast two-hybrid system. Since BIRC3 is important for cell survival, the effect of BIRC3 binding partner Snail on cell survival was investigated in ovarian cancer cell lines. Results revealed that Bax expression was activated, while the expression levels of anti-apoptotic proteins were markedly decreased by small interfering RNA (siRNA) specific for Snail (siSnail). siSnail, the binding partner of siBIRC3, activated the tumour suppressor function of p53 by promoting p53 protein stability. Conversely, BIRC3 could interact with Snail, for this reason, the possibility of BIRC3 involvement in EMT was investigated. BIRC3 overexpression resulted in a decreased expression of the epithelial marker and an increased expression of the mesenchymal markers. siSnail or siBIRC3 reduced the mRNA levels of matrix metalloproteinase (MMP)-2 and MMP-9. These results provide evidence that Snail promotes cell proliferation by interacting with BIRC3 and that BIRC3 might be involved in EMT via binding to Snail in ovarian cancer cells. Therefore, our results suggested the novel relevance of BIRC3, the binding partner of Snail, in ovarian cancer development.

Fibroblast‐specific adipocyte enhancer binding protein 1 is a potential pathological trigger and prognostic marker for liver fibrosis independent of etiology

“…The downregulated genes resulting from AEBP1 silence were significantly enriched in ECM and immune‐related KEGG pathways. Downstream effector genes enriched in ECM‐related pathways such as BIRC3 , ITGA11 , and LAMB3 are known as important regulators of cell survival, proliferation, and activation 40–42 . Among the downstream immune‐related signaling of AEBP1 in HSCs, TNF‐α secreted by fibroblasts modifies neighboring fibroblast cell proliferation by elevating integrin A5 expression; 43 interleukin (IL)‐17 metabolically reprograms activated fibroblasts for proliferation and survival; 44 NF‐κB signaling controls mitogen‐induced proliferation of fibroblasts 45 .…”

“…Downstream effector genes enriched in ECM-related pathways such as BIRC3, ITGA11, and LAMB3 are known as important regulators of cell survival, proliferation, and activation. [40][41][42] Among the downstream immune-related signaling of AEBP1 in HSCs, TNF-α secreted by fibroblasts modifies neighboring fibroblast cell proliferation by elevating integrin A5 expression; 43 interleukin (IL)-17 metabolically reprograms activated fibroblasts for proliferation and survival; 44 NF-κB signaling controls mitogen-induced proliferation of fibroblasts. 45 As expected, NF-κB signaling is the downstream effector of ACLP in HSCs, since the ACLP-NF-κB axis has been widely reported in other cell types.…”

Liver Kinase B1 Mediates Its Anti-Tumor Function by Binding to the N-Terminus of Malic Enzyme 3

“…Luciferase activity in vitro was assayed as previously described ( Rho et al ., 2022 ). Briefly, cells were grown to 85% confluency and co-transfected with promoter luciferase plasmids containing the Renilla luciferase reporter (Promega, Madison, WI, USA) for 24 h. Following lysis with radioimmunoprecipitation buffer, the lysates were cleared by centrifugation at 14,000 rpm for 15 min, and the cell extracts were incubated with the luciferase substrate reagent at room temperature for 30 min according to the manufacturer’s instructions.…”

HPV-18 E7 Interacts with Elk-1 Leading to Elevation of the Transcriptional Activity of Elk-1 in Cervical Cancer

“…At 48 h post-transfection, cells were harvested and lysed on ice in RIPA buffer [50 mM Tris-HCl (pH 8.0), 150 mM NaCl, 1% NP-40, 0.1% SDS, and 0.5% Na-deoxycholate] ( Rho et al ., 2022 ). After centrifugation at 13,000 rpm, the supernatant was incubated with the appropriate antibodies [anti-His (H-3) and anti-E7 (N-19); Santa Cruz Biotechnology, Dallas, TX, USA] overnight at 4°C and then with protein A/G beads (Upstate Biotechnology, Lake Placid, NY, USA) for 3 h. The beads were washed three times with buffer containing 50 mM Tris-HCl (pH 8.0), 1% NP-40, and 2 mM EDTA.…”

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Cervical cancer is the second leading cause of cancer mortality among women worldwide (Łuczak and Jagodzinski, 2008;Chang et al, 2010;Rho et al, 2022). Over the past two decades, numerous studies have suggested that high-risk HPV plays an important role in the development and pathogenesis of cervical cancer (Guo et al, 2011;Arbyn et al, 2021).

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