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Thioredoxin-interacting protein (TXNIP) functions as a tumor suppressor, but its role in lung cancer remains poorly defined. This study identifies TXNIP as a negative regulator of TNF receptor-associated factor 6 (TRAF6)-mediated NF-κB activation and autophagy, key pathways in tumor progression. TXNIP directly binds TRAF6 via its C-terminal arrestin domain, inhibiting TRAF6 dimerization and auto-ubiquitination. This, in turn, reduces ubiquitination of downstream targets TGF-β-activated kinase 1 and beclin 1 (BECN1), thereby suppressing NF-κB signaling and autophagic activity. TXNIP expression is significantly reduced in lung adenocarcinoma and lung squamous cell carcinoma, as demonstrated by public datasets and patient tissue analysis. Gene set enrichment analysis shows that non-small cell lung cancer patients with TXNIPDOWN and TRAF6UP expression exhibit increased metastasis-associated gene signatures and poorer survival outcomes. Functionally, TXNIP-knockout lung cancer cells show enhanced TRAF6 and BECN1 ubiquitination, increased LC3 puncta, and elevated NF-κB activity and cytokine production after TLR3/4 stimulation. These cells also display increased proliferation, migration, invasion, and colony formation in vitro across multiple lung cancer cell lines (A549 and H1299). Collectively, this study highlights TXNIP as a critical suppressor of TRAF6-driven oncogenic pathways in lung cancer, suggesting that its downregulation contributes to disease progression through enhanced TLR-induced signaling.

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기사명 저자명 페이지 원문 목차
TXNIP suppresses lung cancer progression by inhibiting TRAF6-mediated NF-κB activation and autophagy Ji Young Kim, Mi-Jeong Kim, Ji Hye Shin, Kyung-Hwa Baik, Yeeun Kang, Yoolim Sung, Seo Hyun Kim, Ha-Jeong Lee, Chaeeun Lee, Jae-Hyuck Shim, Duk-Hwan Kim, Eunyoung Chun, Ki-Young Lee p. 1-21
IL-22 exacerbates coxsackievirus type B3-induced pancreatitis by elevating viral replication through STAT3 activation Dae-Joon Kim, Jae-Hyoung Song, Jae-Hyeon Jeong, Jae-Hee Ahn, Jaewon Cho, Seo-Hyeon Mun, Eun-Hye Hong, Sungchan Cho, Sun-Young Chang, Dae Hee Kim, Hyun-Jeong Ko p. 1-18
Intestinal dysbiosis caused by epithelial Fabp6 gene disruption exacerbates gut inflammatory disease Kyeongeun Kwon, Minyoung Kim, Youngrak Jung, Mi Young Yoon, June-Yong Lee, Sang Sun Yoon, Mina Rho, Youn Wook Chung, Ji-Hwan Ryu p. 1-24
Unlocking IL-33 : new insights into tumor immunity Byeong Hoon Kang, Heung Kyu Lee p. 1-15
Virus-like particle vaccines containing RSV fusion protein cleavage mutations are immunogenic and protective in cotton rats with a prime dose Hye Suk Hwang, Young-Man Kwon, Ki-Hye Kim, Young-Tae Lee, Eun-Ju Ko, Arun Meas, Sang-Moo Kang p. 1-17
Comprehensive analysis of scRNA-seq and bulk RNA-seq identified TIMP1 as a prognostic marker in colorectal cancer Qian-Wen Luo, Yuan-Chao Shi, Wang-Qiang Jia, Xiao-Hai Zhou, Zheng-Rong Yang, Yan Wang, Quan-Lin Guan p. 1-22

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