Kaposi’s sarcoma (KS) is the most common AIDS-associated malignancy etiologically caused by Kaposi’s sarcoma-associated herpesvirus (KSHV). KS is a highly disseminated and vascularized tumor comprised of poorly differentiated spindle-shaped endothelial cells. KSHV encodes 12 pre-microRNAs (pre-miRNAs) that yield 25 mature miRNAs, but their roles in KSHV-induced tumor dissemination and angiogenesis remain largely unknown. KSHV-encoded miR-K12-6 (miR-K6) can produce two mature miRNAs, miR-K6-3p and miR-K6-5p. Recently, we have shown that miR-K6-3p promoted cell migration and angiogenesis by directly targeting SH3 domain binding glutamate-rich protein (SH3BGR) (PLoS Pathog. 2016;12(4):e1005605). Here, by using mass spectrometry, bioinformatics analysis and luciferase reporter assay, we showed that miR-K6-5p directly targeted the coding sequence (CDS) of CD82 molecule (CD82), a metastasis suppressor. Ectopic expression of miR-K6-5p specifically inhibited the expression of endogenous CD82 and strongly promoted endothelial cells invasion in vitro and angiogenesis in vivo. Overexpression of CD82 significantly inhibited cell invasion and angiogenesis induced by miR-K6-5p. Mechanistically, CD82 directly interacted with c-Met to inhibit its activation. MiR-K6-5p directly repressed CD82, relieving its inhibition on c-Met activation and inducing cell invasion and angiogenesis. Deletion of miR-K6 from KSHV genome abrogated KSHV suppression of CD82 resulting in compromised KSHV activation of c-Met pathway, and KSHV-induced invasion and angiogenesis. In conclusion, these results show that by inhibiting CD82, KSHV miR-K6-5p promotes cell invasion and angiogenesis by activating the c-Met pathway. Our findings illustrate that KSHV miRNAs may play an essential role in the dissemination and angiogenesis of KSHV-induced malignancies.

A series of 80 esophageal cytologic specimens derived from the same number of patients with previously diagnosed squamous cell dysplasia of the esophagus were examined for the presence of human papillomavirus (HPV) infection by filter in situ hybridization (FISH), using a mixed DNA probe containing HPV types 11, 16, and 18. All the patients came from an area at high risk for esophageal cancer in China. A total of 53 cases (66.3%) were demonstrated as HPV-DNA-positive. HPV DNA was detected in 22.2% (2 of 9) of the patients without cytologic atypia, in 50% (3 of 6) with mild dysplasia, in 80.6% (25 of 31) with moderate dysplasia, in 67.9% (19 of 28) with severe dysplasia, and in 66.7% (4 of 6) with an invasive squamous cell carcinoma. The present results confirm the recent findings on HPV involvement in esophageal squamous cell lesions. They support the hypothesis that HPV is a possible etiologic agent in esophageal carcinogenesis, most probably acting synergistically with physical, chemical, and/or nutritional factors that have previously been related with this malignancy in the high-risk areas of China.

Background Fecal incontinence (FI) is a common complaint that seriously affects the quality of life in patients with Crohn’s disease (CD). We aimed to identify risk factors related to FI and construct a risk prediction model for FI in patients with CD. Methods Four hundred and sixty-one patients diagnosed with CD between June 2016 and April 2021 in Jiangsu Province Hospital of Chinese Medicine were retrospectively enrolled in this study and randomly divided into the development (n=368) and internal validation cohort (n=93). FI-related risk factors were selected from the development cohort using the random forest procedure and included in a logistic regression model from which the prediction model was elaborated. The discrimination, calibration and clinical benefit of the model were evaluated by examining the area under the receiver operating characteristic curves, calibration curves and decision curve analysis in internal validation and external validation (using 225 patients from four tertiary hospitals), respectively. Results Four independent variables were selected and included in the logistic regression model: body mass index, history of non-fistulizing perianal lesions surgery, the number of loose stools in the last week and perianal disease activity index. A nomogram was developed to facilitate risk score calculation. The model showed good discrimination ability with AUC was 0.798 and 0.780 in the internal and external cohorts, respectively. The calibration curves demonstrated good agreement with the model using the Hosmer-Lemeshow test in both cohorts (internal validation, P = 0.562; external validation, P = 0.383). DCA confirmed the clinical validity of the predictive model. Conclusion This study recognized four risk factors related to the prevalence of FI and developed a new model to effectively predict risk scores of FI in CD patients, helping to provide early risk stratification and timely intervention.