Simonsson, M., Bergman, S., Jacobsson, L. T., Petersson, I. F. & Svensson, B. The prevalence of rheumatoid arthritis in Sweden. Scand. J. Rheumatol. 28(6), 340–343 (1999).
Google Scholar
van Zeben, D. & Breedveld, F. C. Prognostic factors in rheumatoid arthritis. J. Rheumatol. Suppl. 44, 31–33 (1996).
Google Scholar
Bartok, B. & Firestein, G. S. Fibroblast-like synoviocytes: Key effector cells in rheumatoid arthritis. Immunol. Rev. 233(1), 233–255 (2010).
Google Scholar
Alivernini, S., Firestein, G. S. & McInnes, I. B. The pathogenesis of rheumatoid arthritis. Immunity 55(12), 2255–2270 (2022).
Google Scholar
Muller-Ladner, U. et al. Synovial fibroblasts of patients with rheumatoid arthritis attach to and invade normal human cartilage when engrafted into SCID mice. Am. J. Pathol. 149(5), 1607–1615 (1996).
Google Scholar
Tolboom, T. C. et al. Invasiveness of fibroblast-like synoviocytes is an individual patient characteristic associated with the rate of joint destruction in patients with rheumatoid arthritis. Arthritis Rheum. 52(7), 1999–2002 (2005).
Google Scholar
Laragione, T., Brenner, M., Mello, A., Symons, M. & Gulko, P. S. The arthritis severity locus Cia5d is a novel genetic regulator of the invasive properties of synovial fibroblasts. Arthritis Rheum. 58(8), 2296–2306 (2008).
Google Scholar
Gulko, P. S. Contribution of genetic studies in rodent models of autoimmune arthritis to understanding and treatment of rheumatoid arthritis. Genes Immun. 8(7), 523–531 (2007).
Google Scholar
Laragione, T. & Gulko, P. S. mTOR regulates the invasive properties of synovial fibroblasts in rheumatoid arthritis. Mol Med. 16(9–10), 352–358 (2010).
Google Scholar
Trinh, B. Q., Ko, S. Y., Barengo, N., Lin, S. Y. & Naora, H. Dual functions of the homeoprotein DLX4 in modulating responsiveness of tumor cells to topoisomerase II-targeting drugs. Cancer Res. 73(2), 1000–1010 (2013).
Google Scholar
Zhang, L. et al. Overexpression of BP1, an isoform of Homeobox Gene DLX4, promotes cell proliferation, migration and predicts poor prognosis in endometrial cancer. Gene 707, 216–223 (2019).
Google Scholar
Zhang, L. et al. DLX4 upregulates TWIST and enhances tumor migration, invasion and metastasis. Int. J. Biol. Sci. 8(8), 1178–1187 (2012).
Google Scholar
Man, Y. G. et al. Expression of BP1, a novel homeobox gene, correlates with breast cancer progression and invasion. Breast Cancer Res. Treat. 90(3), 241–247 (2005).
Google Scholar
Zhang, F. et al. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat. Immunol. 20(7), 928–942 (2019).
Google Scholar
Schriml, L. M. et al. Human disease ontology 2018 update: Classification, content and workflow expansion. Nucleic Acids Res. 47(D1), D955–D962 (2019).
Google Scholar
Pinero, J. et al. The DisGeNET knowledge platform for disease genomics: 2019 update. Nucleic Acids Res. 48(D1), D845–D855 (2020).
Google Scholar
Gene Ontology, C. et al. The gene ontology knowledgebase in 2023. Genetics 224(1), iyad031 (2023).
Ashburner, M. et al. Gene ontology: Tool for the unification of biology. Gene Ontol. Consortium. Nat. Genet. 25(1), 25–29 (2000).
Google Scholar
Ogata, H. et al. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 27(1), 29–34 (1999).
Google Scholar
Kanehisa, M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 28(11), 1947–1951 (2019).
Google Scholar
Kanehisa, M. & Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28(1), 27–30 (2000).
Google Scholar
Milacic, M. et al. The reactome pathway knowledgebase 2024. Nucleic Acids Res. 52(D1), D672–D678 (2024).
Google Scholar
Liu, Y. & Xiong, Y. HADHA promotes ovarian cancer outgrowth via up-regulating CDK1. Cancer Cell Int. 23(1), 283 (2023).
Google Scholar
Liu, Y. et al. MiR-612 regulates invadopodia of hepatocellular carcinoma by HADHA-mediated lipid reprogramming. J. Hematol. Oncol. 13(1), 12 (2020).
Google Scholar
Ma, M. et al. UBE2O promotes lipid metabolic reprogramming and liver cancer progression by mediating HADHA ubiquitination. Oncogene 41(48), 5199–5213 (2022).
Google Scholar
Shi, D., Lin, B., Lai, J., Li, K. & Feng, Y. Upregulation of CPNE3 suppresses invasion, migration and proliferation of glioblastoma cells through FAK pathway inactivation. J. Mol. Histol. 52(3), 589–596 (2021).
Google Scholar
Lin, H. C. et al. Quantitative proteomic analysis identifies CPNE3 as a novel metastasis-promoting gene in NSCLC. J. Prot. Res. 12(7), 3423–3433 (2013).
Google Scholar
Lin, H. et al. CPNE3 promotes migration and invasion in non-small cell lung cancer by interacting with RACK1 via FAK signaling activation. J. Cancer 9(22), 4215–4222 (2018).
Google Scholar
Tsujinaka, S., Soda, K., Kano, Y. & Konishi, F. Spermine accelerates hypoxia-initiated cancer cell migration. Int. J. Oncol. 38(2), 305–312 (2011).
Google Scholar
Zhou, L. et al. miR-942-5p inhibits proliferation, metastasis, and epithelial-mesenchymal transition in colorectal cancer by targeting CCBE1. Biomed. Res. Int. 2021, 9951405 (2021).
Google Scholar
Mizoguchi, F. et al. Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis. Nat. Commun. 9(1), 789 (2018).
Google Scholar
Tolboom, T. C. et al. Invasive properties of fibroblast-like synoviocytes: Correlation with growth characteristics and expression of MMP-1, MMP-3, and MMP-10. Ann. Rheum. Dis. 61(11), 975–980 (2002).
Google Scholar
Laragione, T., Harris, C. & Gulko, P. S. TRPV2 suppresses Rac1 and RhoA activation and invasion in rheumatoid arthritis fibroblast-like synoviocytes. Int. Immunopharmacol. 70, 268–273 (2019).
Google Scholar
Laragione, T. et al. Huntingtin-interacting protein 1 (HIP1) regulates arthritis severity and synovial fibroblast invasiveness by altering PDGFR and Rac1 signalling. Ann. Rheum. Dis. 77(11), 1627–1635 (2018).
Google Scholar
Tanner, M. R. et al. KCa1.1 inhibition attenuates fibroblast-like synoviocyte invasiveness and ameliorates disease in rat models of rheumatoid arthritis. Arthritis Rheumatol. 67(1), 96–106 (2015).
Google Scholar
Laragione, T., Brenner, M., Sherry, B. & Gulko, P. S. CXCL10 and its receptor CXCR3 regulate synovial fibroblast invasion in rheumatoid arthritis. Arthritis Rheum. 63(11), 3274–3283 (2011).
Google Scholar
Tomida, S. et al. Identification of a metastasis signature and the DLX4 homeobox protein as a regulator of metastasis by combined transcriptome approach. Oncogene 26(31), 4600–4608 (2007).
Google Scholar
Gu, J., Wang, Z., Wang, B. O. & Ma, X. ImmuneScore of eight-gene signature predicts prognosis and survival in patients with endometrial cancer. Front. Oncol. 13, 1097015 (2023).
Google Scholar
Han, Z., Boyle, D. L., Shi, Y., Green, D. R. & Firestein, G. S. Dominant-negative p53 mutations in rheumatoid arthritis. Arthritis Rheum. 42(6), 1088–1092 (1999).
Google Scholar
Kinne, R. W. et al. Synovial fibroblast-like cells strongly express jun-B and C-fos proto- oncogenes in rheumatoid- and osteoarthritis. Scand J. Rheumatol. Suppl. 101, 121–125 (1995).
Google Scholar
Trabandt, A., Gay, R. E. & Gay, S. Oncogene activation in rheumatoid synovium. APMIS 100(10), 861–875 (1992).
Google Scholar
Trabandt, A. et al. Expression of the collagenolytic and Ras-induced cysteine proteinase cathepsin L and proliferation-associated oncogenes in synovial cells of MRL/I mice and patients with rheumatoid arthritis. Matrix 10(6), 349–361 (1990).
Google Scholar
Case, J. P., Lafyatis, R., Remmers, E. F., Kumkumian, G. K. & Wilder, R. L. Transin/stromelysin expression in rheumatoid synovium. A transformation- associated metalloproteinase secreted by phenotypically invasive synoviocytes. Am. J. Pathol. 135(6), 1055–1064 (1989).
Google Scholar
Laragione, T., Brenner, M., Li, W. & Gulko, P. S. Cia5d regulates a new fibroblast-like synoviocyte invasion-associated gene expression signature. Arthritis Res. Ther. 10(4), R92 (2008).
Google Scholar
Firestein, G. S., Echeverri, F., Yeo, M., Zvaifler, N. J. & Green, D. R. Somatic mutations in the p53 tumor suppressor gene in rheumatoid arthritis synovium. Proc. Natl. Acad. Sci. U. S. A. 94(20), 10895–10900 (1997).
Google Scholar
Aupperle, K. R. et al. Regulation of synoviocyte proliferation, apoptosis, and invasion by the p53 tumor suppressor gene. Am. J. Pathol. 152(4), 1091–1098 (1998).
Google Scholar
Sun, Y., Wenger, L., Rutter, J. L., Brinckerhoff, C. E. & Cheung, H. S. p53 down-regulates human matrix metalloproteinase-1 (Collagenase-1) gene expression. J. Biol. Chem. 274(17), 11535–11540 (1999).
Google Scholar
Chan, A. et al. The GTPase rac regulates the proliferation and invasion of fibroblast-like synoviocytes from rheumatoid arthritis patients. Mol. Med. 13(5–6), 297–304 (2007).
Google Scholar
Brenner, M., Laragione, T. & Gulko, P. S. Analyses of synovial tissues from arthritic and protected congenic rat strains reveal a new core set of genes associated with disease severity. Physiol. Genomics. 45(22), 1109–1122 (2013).
Google Scholar
Clanchy, F. I. L. et al. TLR expression profiles are a function of disease status in rheumatoid arthritis and experimental arthritis. J. Autoimmun. 118, 102597 (2021).
Google Scholar
Brentano, F., Kyburz, D., Schorr, O., Gay, R. & Gay, S. The role of Toll-like receptor signalling in the pathogenesis of arthritis. Cell Immunol. 233(2), 90–96 (2005).
Google Scholar
Seibl, R. et al. Expression and regulation of Toll-like receptor 2 in rheumatoid arthritis synovium. Am. J. Pathol. 162(4), 1221–1227 (2003).
Google Scholar
Chen, S. Y. et al. Suppression of collagen-induced arthritis by intra-articular lentiviral vector-mediated delivery of Toll-like receptor 7 short hairpin RNA gene. Gene Ther. 19(7), 752–760 (2012).
Google Scholar
Ramirez-Perez, S. et al. MyD88 dimerization inhibitor ST2825 targets the aggressiveness of synovial fibroblasts in rheumatoid arthritis patients. Arthritis Res. Ther. 25(1), 180 (2023).
Google Scholar
McGarry, T. et al. Toll-like receptor 2 (TLR2) induces migration and invasive mechanisms in rheumatoid arthritis. Arthritis Res. Ther. 17(1), 153 (2015).
Google Scholar
Huang, B., Zhao, J., Unkeless, J. C., Feng, Z. H. & Xiong, H. TLR signaling by tumor and immune cells: a double-edged sword. Oncogene 27(2), 218–224 (2008).
Google Scholar
Mukherjee, S. et al. Toll-like receptor-guided therapeutic intervention of human cancers: Molecular and immunological perspectives. Front. Immunol. 14, 1244345 (2023).
Google Scholar
Merrell, M. A. et al. Toll-like receptor 9 agonists promote cellular invasion by increasing matrix metalloproteinase activity. Mol. Cancer Res. MCR. 4(7), 437–447 (2006).
Google Scholar
Xun, Y., Yang, H., Kaminska, B. & You, H. Toll-like receptors and toll-like receptor-targeted immunotherapy against glioma. J. Hematol. Oncol. 14(1), 176 (2021).
Google Scholar
Jawed, S., Gaffney, K. & Blake, D. R. Intra-articular pressure profile of the knee joint in a spectrum of inflammatory arthropathies. Ann. Rheum. Dis. 56(11), 686–689 (1997).
Google Scholar
Ng, C. T. et al. Synovial tissue hypoxia and inflammation in vivo. Ann. Rheum. Dis. 69(7), 1389–1395 (2010).
Google Scholar
Quinonez-Flores, C. M., Gonzalez-Chavez, S. A. & Pacheco-Tena, C. Hypoxia and its implications in rheumatoid arthritis. J. Biomed. Sci. 23(1), 62 (2016).
Google Scholar
Hu, F. et al. Hypoxia and hypoxia-inducible factor-1alpha provoke toll-like receptor signalling-induced inflammation in rheumatoid arthritis. Ann. Rheum. Dis. 73(5), 928–936 (2014).
Google Scholar
Campbell, N. K., Fitzgerald, H. K. & Dunne, A. Regulation of inflammation by the antioxidant haem oxygenase 1. Nat. Rev. Immunol. 21(7), 411–425 (2021).
Google Scholar
Chora, A. A. et al. Heme oxygenase-1 and carbon monoxide suppress autoimmune neuroinflammation. J. Clin. Invest. 117(2), 438–447 (2007).
Google Scholar
Kapturczak, M. H. et al. Heme oxygenase-1 modulates early inflammatory responses: Evidence from the heme oxygenase-1-deficient mouse. Am. J. Pathol. 165(3), 1045–1053 (2004).
Google Scholar
Guan, Y., Zhao, X., Liu, W. & Wang, Y. Galuteolin suppresses proliferation and inflammation in TNF-alpha-induced RA-FLS cells by activating HMOX1 to regulate IKKbeta/NF-kappaB pathway. J. Orthop. Surg. Res. 15(1), 484 (2020).
Google Scholar
Sun, M. et al. Asiatic acid induces ferroptosis of RA-FLS via the Nrf2/HMOX1 pathway to relieve inflammation in rheumatoid arthritis. Int. Immunopharmacol. 137, 112394 (2024).
Google Scholar
Ren, Q. G. et al. Low heme oxygenase-1 expression promotes gastric cancer cell apoptosis, inhibits proliferation and invasion, and correlates with increased overall survival in gastric cancer patients. Oncol. Rep. 38(5), 2852–2858 (2017).
Google Scholar
Zhao, Z., Xu, Y., Lu, J., Xue, J. & Liu, P. High expression of HO-1 predicts poor prognosis of ovarian cancer patients and promotes proliferation and aggressiveness of ovarian cancer cells. Clin. Transl. Oncol. 20(4), 491–499 (2018).
Google Scholar
Padilla, J. & Lee, J. A novel therapeutic target, BACH1, regulates cancer metabolism. Cells 10(3), 634 (2021).
Google Scholar
Hsu, F. F. et al. Signal peptide peptidase-mediated nuclear localization of heme oxygenase-1 promotes cancer cell proliferation and invasion independent of its enzymatic activity. Oncogene 34(18), 2360–2370 (2015).
Google Scholar
Gandini, N. A. et al. Heme oxygenase-1 has an antitumor role in breast cancer. Antioxid Redox. Signal. 30(18), 2030–2049 (2019).
Google Scholar
Laragione, T. et al. The cation channel Trpv2 is a new suppressor of arthritis severity, joint damage, and synovial fibroblast invasion. Clin. Immunol. 158(2), 183–192 (2015).
Google Scholar
Laragione, T., Harris, C. & Gulko, P. S. KIF1C and new Huntingtin-interacting protein 1 binding proteins regulate rheumatoid arthritis fibroblast-like synoviocytes’ phenotypes. Front. Immunol. 15, 1323410 (2024).
Google Scholar
Goedhart, J. & Luijsterburg, M. S. VolcaNoseR is a web app for creating, exploring, labeling and sharing volcano plots. Sci. Rep. 10(1), 20560 (2020).
Google Scholar