Dataset Information

C-Myb interferes with inflammatory IL1α-NF-κB pathway in breast cancer cells.

ABSTRACT: The transcription factor c-Myb can be involved in the activation of many genes with protumorigenic function; however, its role in breast cancer (BC) development is still under discussion. c-Myb is considered as a tumor-promoting factor in the early phases of BC, on the other hand, its expression in BC patients relates to a good prognosis. Previously, we have shown that c-Myb controls the capacity of BC cells to form spontaneous lung metastasis. Reduced seeding of BC cells to the lungs is linked to high expression of c-Myb and a decline in expression of a specific set of inflammatory genes. Here, we unraveled a c-Myb-IL1α-NF-κB signaling axis that takes place in tumor cells. We report that an overexpression of c-Myb interfered with the activity of NF-κB in several BC cell lines. We identified IL1α to be essential for this interference since it was abrogated in the IL1α-deficient cells. Overexpression of IL1α, as well as addition of recombinant IL1α protein, activated NF-κB signaling and restored expression of the inflammatory signature genes suppressed by c-Myb. The endogenous levels of c-Myb negatively correlated with IL1α on both transcriptional and protein levels across BC cell lines. We concluded that inhibition of IL1α expression by c-Myb reduces NF-κB activity and disconnects the inflammatory circuit, a potentially targetable mechanism to mimic the antimetastatic effect of c-Myb with therapeutic perspective.

SUBMITTER: Ducka M

PROVIDER: S-EPMC7905261 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

c-Myb interferes with inflammatory IL1α-NF-κB pathway in breast cancer cells.

Dúcka Monika M Kučeríková Martina M Trčka Filip F Červinka Jakub J Biglieri Elisabetta E Šmarda Jan J Borsig Lubor L Beneš Petr P Knopfová Lucia L

Neoplasia (New York, N.Y.) 20210220 3

The transcription factor c-Myb can be involved in the activation of many genes with protumorigenic function; however, its role in breast cancer (BC) development is still under discussion. c-Myb is considered as a tumor-promoting factor in the early phases of BC, on the other hand, its expression in BC patients relates to a good prognosis. Previously, we have shown that c-Myb controls the capacity of BC cells to form spontaneous lung metastasis. Reduced seeding of BC cells to the lungs is linked ...[more]

PMID: 33621853

Similar Datasets

Project description:Scoparone (SCO) is a compound found in the stems and leaves of Artemisia capillaris. The pharmacological uses of SCO include significant hypotensive, cholagogic, anti-inflammatory, analgesic, lipid-lowering, anti-asthmatic and anti-coagulant effects. The present study aimed to verify the anticancer potential of SCO in breast cancer (BC) cells and its underlying molecular mechanism. Cell Counting Kit-8 and flow cytometry were used to analyze the effects of SCO on cell viability and apoptosis. Nucleocytoplasmic separation was used to analyze the location of the long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) in BC cells. Reverse transcription-quantitative PCR was used to analyze the effect of SCO on the expression levels of SNHG12, microRNA (miRNA/miR)-140-3p and tumor necrosis factor receptor associated factor 2 (TRAF2). Western blotting was used to analyze the protein expression levels of TRAF2 and downstream nuclear factor κB (NF-κB) signaling pathways. The results demonstrated that SCO had a time- and dose-dependent inhibitory effect on the viability of BC cells, and that the upregulated lncRNA SNHG12 in BC cells was inhibited by SCO. SNHG12, which was primarily expressed in the cytoplasm, acted as a competing endogenous RNA, sponged miR-140-3p and inhibited the expression of miR-140-3p. The transcriptional activity and translational level of TRAF2, a downstream target of miR-140-3p, decreased following the SCO-mediated suppression of SNHG12 expression. As an upstream effector, TRAF2 activity reduction mediated the inhibition of NF-κB signaling, decreased the viability and migration of BC cells, and promoted BC cell apoptosis. In conclusion, SCO-induced inhibition of viability and promotion of apoptosis in BC cells are achieved through the inhibition of NF-κB signaling, which is associated with regulation of the SNHG12/miR-140-3p/TRAF2 axis. This understanding provides new drug candidates for the treatment of BC and a theoretical basis for biology.

Dataset Information

C-Myb interferes with inflammatory IL1α-NF-κB pathway in breast cancer cells.

Publications

c-Myb interferes with inflammatory IL1α-NF-κB pathway in breast cancer cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets