Fig 2: miR-181b regulates the proliferation of SFCs through CYLD. a Soft agar experiment was employed analyze the relationship between miR-181b and CYLD. Colonies were counted following 0.5 % crystal violet staining. The experiments were performed three times independently. Scale bar = 10 mm. b STAT3 and miR-181b expression levels in esophageal cancer, with each data point representing an individual sample. c miR-181b and CYLD expression levels in esophageal cancer, with each data point representing an individual sample. Spearman analysis were employed to analyzed the relationship between STAT3 and miR-181b, miR-181b and CYLD

Fig 3: Overexpression of FLAP correlates to CYLD suppression in resection tissues of HCC patients. (A) Representative immunohistochemistry (IHC) images of FLAP, MGST2, CysLTR2, and CYLD in each subject using the indicated antibodies. Scale bar = 20 μm, bar = 10 μm (magnification). (B) The expression levels of FLAP, mGST2, CysLTR2, and CYLD were clustered. Patient and donor codes are indicated. Grades of the indicated markers (Red: ++ = brown, Blue: + = golden, Green: ND = not detected). (C) The expression levels of CD34 localization and positive rate (%) for Ki-67 were clustered. Patient and donor codes are matched with each other. For each analysis, n = 10/per group.

Fig 4: EBV inhibits CYLD expression and contributes to tumorigenesis in NPC.a Representative IHC staining of CYLD expression from pathological sections of NPC patients (100×: scale bar, 100 µm; 400×: scale bar, 50 µm). b Histoscores of CYLD expression in NPC patients (n = 29) compared to nasopharyngeal (NP) tissue (n = 20). c Overall survival and d Progression free survival rates of NPC patients with low (n = 71) or high (n = 58) expression levels of CYLD were estimated by the Kaplan–Meier method using log-rank test. Group according to CYLD median expression. e mRNA and f protein expression of CYLD in NP460/NP460-EBV, HK1/HK1-EBV, and HONE1/HONE1-EBV cell lines. g DUB activity measurement of CYLD in HK1/HK1-EBV, HONE1/HONE1-EBV cells. h HK1-EBV and HONE1-EBV cells were infected with a lentivirus and proliferation was monitored using CCK8 assays at the indicated time points. Statistical significance was determined by a two-tailed, unpaired Student’s t test. The indicated cells (5 × 106) were subcutaneously injected into mice. i CYLD activity in tumor extracts. j Tumor growth, k tumor weight, and l tumor images are shown. (Data are represented as mean ± SEM (n = 3). Differences were considered significant at *p < 0.05, **p < 0.001, ***p < 0.001).

Fig 5: Enhanced hepatic FLAP mRNA shortens median survival time of HCC patients after surgical resection. Data for either HCC patients after surgical resection or liver transplantation from the TCGA Research Network (http://cancergenome.nih.gov/) were eligible for survival analysis. (A–D) Left panels: Kaplan–Meier survival curves in coordinate axis for comparing survival rates between high- and low-gene transcription subgroups from the HCC cohort. Horizontal dotted line: 50% survival. Vertical red/blue dotted lines: median survival time (MST). (A) FLAP mRNA (p = 0.0470). (B) mGST2 mRNA (p = 0.2697). (C) CysLTR2 mRNA (p = 0.0418). (D) CYLD mRNA (p = 0.0456). Right panels: Scattered plots of transcription levels for indicating genes from the HCC cohort. Student unpaired t-test was used to compare groups and p-value less than 0.05 was considered as statistically significant.