JunB can enhance the transcription of IL‐8 in oral squamous cell carcinoma

Abstract

Proteasome inhibitor MG132 was shown to enhance the secretion of interleukin 8 (IL-8) by various cells. The enhancement is regulated by the transcription factor activator protein-1 (AP-1) at the transcriptional level. AP-1 is a dimer formed by AP-1 family proteins. The purpose of the present study was to explore the combinations of the AP-1 family proteins that contribute to MG132-driven IL-8 secretion. Oral squamous cell carcinoma-derived cell lines, Ca9-22 and HSC3, were used to demonstrate their response to MG132. IL-8 secretion was augmented by MG132 in both cell lines. c-Jun expression was detected in both the cell lines, whereas c-Fos expression was detected only in the HSC3. The influence of MG132 stimulation on c-Jun and c-Fos expression was further examined by western blot analysis. c-Jun expression was increased by MG132 stimulation, whereas c-Fos expression was not detected even after MG132 stimulation. As JunB is reported to inhibit the transcriptional activity of the AP-1 complex, we speculated that the c-Jun homodimer should contribute to IL-8 enhancement. Expression vectors encoding wild type and c-Jun mutants, M17 and M22-23, respectively, were constructed and transfected into the Ca9-22 cells. In contrast to our expectations, MG132-induced IL-8 secretion was significantly reduced in all the transfectants suggesting that other c-Jun members might form homodimers with c-Jun and contribute to IL-8 enhancement. Transfection of the cells with c-Jun or JunB small hairpin RNA (shRNA) reduced IL-8 secretion up to 50% and 65% of the control shRNA transfectant. Furthermore, cotransfection of both shRNA almost completely inhibited the IL-8 secretion. These results indicate that JunB not only inhibits but also enhances the transcription of c-Jun targets in combination with c-Jun.

Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response

“…SCENIC analysis identified the upregulation of several proto-oncogenic TFs CEBPA, JUNB, and KLF4 (ref. [16][17][18] ), and tumor suppressor TFs GRHL1 and RCOR1 (ref. 19,20 ) in the TC (Extended Data Fig.…”

Osteogenic differentiation of mesenchymal stem cells promotes c-Jun-dependent secretion of interleukin 8 and mediates the migration and differentiation of CD4+ T cells

“…However, interfering with the expression of c-Jun could effectively rescue the above phenomena. Furthermore, previous studies have revealed that the transcription factor c-Jun not only regulates the secretion of IL-8 [ 39 – 41 ] but also acts as a key transcription factor that regulates the secretion of other essential immunoregulatory factors, such as VEGF, PDGFA and HGF, by MSCs [ 20 ]. Abnormal differentiation and a decline in the immunoregulatory capacity of MSCs have been found in many autoimmune diseases, such as AS [ 21 , 42 , 43 ], rheumatoid arthritis (RA) [ 44 – 46 ], and systemic lupus erythematosus (SLE) [ 47 , 48 ].…”

Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response

“…SCENIC analysis identified the upregulation of several proto-oncogenic TFs CEBPA, JUNB, and KLF4 (ref. [18][19][20] ), and tumor suppressor TFs GRHL1 and RCOR1 (ref. 21,22 ) in the tumor core (Extended Data Fig.…”