Fig 2: Expression of RhoA in synovial tissues extracted from RA patients. The expression of RhoA in RA (A and B) and CIA (C and D) synovial fibroblasts was analyzed by single cell data (data from Nature. 2020; 528: 259–264) (E) The expression of RhoA in synovial tissue of RA and Normal (transcriptome data from NCBI) (F) Representative photomicrographs showing the localisation of RhoA in synovial tissue sections from RA patients and Normal group (G) Quantification of RhoA in the synovial of RA synovium versus Normal synovium (n ​= ​6) (H) Representative western blot showing RhoA and HIF-1α protein in Normal group versus RA synovial tissue. GAPDH was used as loading control. Bars show the mean ​± ​SEM. ∗p ​< ​0.05, versus control patients.

Fig 3: Repertaxin attenuates in vitro progression of the colitic phenotype in iHUCOs.a, b Representative dual IF staining for CXCR1 (red) and CXCL8 (green) expressed in epithelium and mesenchyme of iHN and iHUC organoids in the absence or presence of repertaxin. c, d Violin plots of cells expressing CXCR1, CXCL8, and both (overlap), in the epithelium and mesenchyme of normal and UC organoids with or without (Ctrl) treatment with 20 µM repertaxin. e, f Representative H&E of iHNO and iHUCO with and without repertaxin treatment. g, h Summarized average diameter and percentage of epithelial structure type in organoids after 21 days, with and without repertaxin treatment. Violin plots in g compare iHNO control (ctrl) vs. 20 μm repertaxin treatment. In panel h, the epithelial structure is compared between iHNO and iHUCO in the presence or absence of 20 μm repertaxin. The median value is indicated in the center of the box plot. The whiskers above and below the plot represent 1 standard deviation (SD) above and below the mean of the data, respectively. i, j, m, n Representative IHC for β-catenin and E-cadherin in control and repertaxin-treated iHNOs and iHUCOs revealing altered cellular localization of the proteins after repertaxin treatment. k, l, o, p percentage distribution of the cells positive for β-catenin and E-cadherin according to the sub-cellular compartment; plasma membrane only (Mem) or membrane extended to cytoplasm and nucleus (Cyt + Nuc) with or without repertaxin treatment of the organoids. q, r Representative IHC for RhoA in the organoids shows the changes in cellular localization based on repertaxin treatment. s, t Violin plots for the cells expressing RhoA in control and repertaxin-treated organoids according to subcellular compartment: plasma membrane only (Mem) or cytoplasm (Cyt). u Schematic representation of the mechanism underlying the changes in epithelial intercellular junction in iHUCOs with and without repertaxin treatment. IHC Scale bar = 40 μm. IF scale bar = 25 μm. n = 5 iHNOs and n = 6 iHUCOs, respectively. For all comparisons, the unpaired, non-parametric, two-sided Mann–Whitney U test was used to test the difference between percentages of enumerated observations. Source data are provided as a Source Data file.

Fig 4: Network analysis in a Korean GC RNA-Seq dataset shows an underlying GC tumor oncogenetic network, under various signaling contextsA. PATHOME analysis of Korean GC dataset GSE36968 resulted in 31 functional clusters consisting of significant KEGG subpathways. The clusters were assigned to their corresponding KEGG pathway titles. The network diagram showed upregulated genes in red and downregulated genes in green (left panel), and the designated KEGG pathway titles noted in the right table. The network contained RHOA as a “cross-junction” involved in several pathways (see details in the main text). Pathways related to RHOA are marked red. B. From previous Asian GC samples (deposited in GEO; GSE36968), RHOA expression was inspected throughout GC tumor stages. The x-axis represents stage, and the y-axis log2-scaled RPKM. Stage I patients showed higher RHOA gene expression compared to other stage patients, including normal controls.

Fig 5: Clinical relevance of the MYBL2/RACGAP1/YAP axis in human PCa. (A) Representative images of MYBL2, RACGAP1, YAP1, and p-YAP1 IHC staining in 132 breast cancer patient specimens. Scale bars: 50 μm. (B) Percentage of PCa specimens showing MYBL2 expression relative to the level of RACGAP1 and nuclear YAP1 (χ2 test). ***P < 0.001. (C) Kaplan-Meier survival analysis of patients with PCa (n = 132). The log-rank test P-values are shown. (D) Model: overexpression of MYBL2 stimulates the YAP signaling through inducing RACGAP1-mediated RhoA activation, ultimately leading to castration-resistant growth and bone metastasis in PCa.