Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Objective:To investigate the role of Linc00339 in the development of triple-negative breast cancer and its related molecular mechanisms.Methods:The expression levels of Linc00339 in human normal breast epithelial cells and breast cancer cells were detected by real time fluorescent quantitative polymerase chain reaction (qRT-PCR). The Linc00339 was overexpressed in MDA-MB-231 cells by plasmid transfection test; the activity of MDA-MB-231 cells was detected by methyl thiazolyl tetrazolium (MTT) method; the adhesion, invasion and migration ability of MDA-MB-231 cells were detected by adhesion test and transwell test respectively; Western blot was used to detect the expression of APC and Wnt/β-catenin signaling pathway-related proteins in MDA-MB-231 cells. qRT-PCR was used to detect the expression of miRNA-135a, miRNA-135b and miRNA-138 in MDA-MB-231 cells. MDA-MB-231 cells were successfully transfected into nude mice to establish tumor-bearing nude mice model. The volume and weight of tumor were observed and measured. The expression levels of APC, Wnt/β - catenin signaling pathway related proteins were detected by Western blot, and the expression levels of miRNA-135a, miRNA-135b and miRNA-138 were detected by qRT-PCR.Results:Compared with the normal breast epithelial cell group (Hs578Bst), the expression level of Linc00339 in breast cancer cell lines (MCF-7, MDA-MB-468, MDA-MB-231) was significantly up-regulated, especially MDA-MB-231. The results of transfection experiments showed that the expression level of Linc00339 and cell viability were significantly up-regulated in the Linc00339 group compared with the pcDNA3.1 group. The overexpression of Linc00339 significantly increased the proliferation, adhesion and migration and invasion ability of MDA-MB-231 cells, as well as increased the volume and weight of tumor mass in tumor-bearing nude mice. Western blot results showed that Linc00339 overexpression can down-regulate APC protein expression and up-regulate Wnt/β-catenin signaling protein expression. Meanwhile, qRT-PCR results indicated Linc00339 overexpression can up-regulate miRNA-135b expression levels without affecting miRNA-135a and miRNA-138.Conclusions:This study demonstrated that Linc00339 may promote the development and progression of triple-negative breast cancer via the miR-135b/APC-mediated Wnt/β-catenin signaling pathway.