STMN2/NF-κB axis drives tumor growth in thyroid carcinoma

Abstract

Abstract Backgrounds: Stathmin 2 (STMN2) is involved in microtubule dynamics and signal transduction. Highly expressed STMN2 has been reported in various tumors. And yet its role in Thyroid carcinoma (THCA) remained unexplored. Methods: The expressed status of STMN2 in pan-cancer including THCA was evaluated using the TCGA and GETx dataset. Furthermore, the association of STMN2 with the clinical phenotypes was visualized based on TCGA-THCA clinical samples. Gene set enrichment analysis (GESA) was used to enrich STMN2-related signaling pathways. The THCA cell proliferation were examined when STMN2 overexpression or knockout. In vivo assays were undertaken to verify the impact of STMN2 knockout on THCA tumor growth. Luciferase reporter assays were conducted to determine whether STMN2 exerted its role through NF-κB signaling pathway. Results: STMN2 expression levels were differentiated in different cancers. We found that STMN2 was richly expressed in THCA patient-derived specimens based on bioinformatics anlaysis. Functionally, STMN2 enforced expression hastened the THCA cell proliferation, while CRISPR-cas9 depletion of STMN2 retarded tumorigenesis in vitro and in vivo. Mechanically, highly expressed STMN2 increased NF-κB transcriptional activity as well as accumulated IκBa expression in THCA cells, while STMN2 knockout presented an opposite phenomenon. However, PDTC exposure almost abrogated the increased IκBa expression in STMN2-overexpressing THCA cells. Conclusion: we found STMN2 is an oncogenic driver of THCA by activating NF-κB signaling pathway, potentially paving an alternative avenue for THCA management.