Fig 2: IL-6 notably accelerated tumor growth and activated JAK2/STAT3-Sox4-NLRP3 pathway in nude mouse xenografts of OSCC. SCC-15 cells were applied to construct nude mouse xenografts, which were intervened with IL-6 or anti-IL-6. (A) Subcutaneous tumors were dissected and photographed at the end of day 21. (B) Tumor growth curve was presented after xenotransplantation. Sox4 (C) and NLRP3 (D) expressions were certified with RT-qPCR. (E) Immunohistochemical staining of Sox4, NLRP3, and Ki-67 expressions in the tumors. (F) Ki-67 positive cells were counted. (G) Western blotting analysis of JAK2, STAT3, Sox4, and NLRP3 inflammasome activation-related proteins. (H) IL-1β and IL-18 levels were confirmed using ELISA kits in the serum of nude mice. ** P < 0.01, *** P < 0.001

Fig 3: Knockdown of NLRP3 notably weakened proliferation and NLRP3 inflammasome activation in IL-6-mediated OSCC cells. NLRP3 was silenced in SCC-15 and SCC-25 cells, which were addressed with 25 ng/ml IL-6. NLRP3 expression was assessed through RT-qPCR (A) and western blot (B). Cell proliferation was determined via (C) CCK-8, (D) EdU staining and (E) colony formation. (F) The expressions of the inflammation-related proteins were monitored with Western blot. (G) ELISA kits were applied to identify IL-1β and IL-18 levels. *** P < 0.001 vs. IL-6 group; ### P < 0.001 vs. IL-6 + shCTRL group

Fig 4: Schematic overview of the mechanistic basis for the observed study results. IL-6 plays an oncogenic role in OSCC progression by activating JAK2/STAT3/Sox4/NLRP3 pathway. IL-6 could accelerate OSCC cell proliferation by activating inflammasome via JAK2/STAT3/Sox4/NLRP3 pathways. STAT3 played as a transcription factor which positively regulated Sox4, and IL-6 promotes Sox4 expression by activating JAK2/STAT3 pathway. IL-6 could promote proliferation and NLRP3 inflammasome activation via JAK2/STAT3/Sox4 pathway in OSCC cells

Fig 5: IL-6 observably accelerated proliferation and NLRP3 inflammasome activation by JAK2/STAT3 pathway in OSCC cells. SCC-15 and SCC-25 cells were processed with 5 μmol/L JAK2 inhibitor (Fedratinib) and 25 μmol/L STAT3 inhibitor (Protosappanin A), and induced by 25 ng/ml IL-6 for 24 h. The expression change of Sox4 was monitored using RT-qPCR (A) and Western blot (B). Cell proliferation was also tested using (C) CCK-8, (D) EdU staining and (E) colony formation. (F) The levels of inflammation-related proteins were assessed with Western blot. (G) ELISA kits were adopted to examine the concentration of IL-1β and IL-18 in the processed OSCC cells. *** P < 0.001 vs. control group; ## P < 0.01 vs. IL-6 group