Aim: Transplantation of mesenchymal stem cells (MSCs) for the treatment of diabetic erectile dysfunction (ED) is hampered by apoptosis of the transplanted cells. In diabetic ED, there is increased oxidative stress and decreased NO in the corpora cavernosa, and reactive oxygen species (ROS) induce apoptosis of the transplanted cells. In this study we examined whether and how autophagy was involved in ROS-induced apoptosis of MSCs. Methods: Mouse C3H10 MSCs were treated with H 2 O 2 to simulate the high oxidative condition in diabetic ED. Cell viability was measured using MTT assay. Apoptosis was analyzed by flow cytometry. Apoptosis-and autophagy-related proteins were detected with Western blot assays. Intracellular autophagosome accumulation was studied using transmission electron microscopy.

High-mobility group box 1 (HMGB1) has been found to mediate autophagy during chemotherapy in several cancers. However, whether HMGB1plays a role in autophagy and chemoresistance in bladder cancer is elusive. In this report, HMGB1 expression was found to be increased in 30 primary bladder cancer tissue specimens compared to their matched adjacent non-tumor tissues. While gemcitabine induced apoptotic cell death, it also induced HMGB1 expression and autophagy in bladder cancer T24 and BIU-87 cells. Suppressing HMGB1 expression with siRNA strongly potentiated gemcitabine-induced apoptosis. HMGB1 siRNA or autophagy inhibitors suppressed gemcitabine-induced autophagy. Further, gemcitabine activated c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinase (ERK) and Bcl-2 phosphorylation, and blocking ERK and JNK inhibited autophagy and increased apoptosis in gemcitabine-treated cells. Interestingly, suppressing HMGB1 expression attenuated gemcitabine-induced ERK and JNK activation and Bcl-2 phosphorylation. Thus, our results suggest that while gemcitabine kills bladder cancer cells through apoptosis, a cytoprotective autophagy is also induced involving HMGB1-mediated JNK and ERK to counteract the cytotoxicity of gemcitabine, and intervention targeting this pathway may improve the anticancer efficacy of gemcitabine against bladder cancer.

Background To elucidate the correlations between tumor microenvironment and clinical characteristics as well as prognosis in clear cell renal cell cancer (ccRCC) and investigate the immune-associated genes by a comprehensive analysis of The Cancer Genome Atlas (TCGA) database. Methods We collected mRNA expression profiles of 537 ccRCC samples from the TCGA database. Immune scores and stromal scores were calculated by applying the ESTIMATE algorithm. We evaluated the correlation between immune/stromal scores and clinical characteristics as well as prognosis. The differentially expressed genes (DEGs) were screened between high immune/stromal score and low immune/stromal score groups by the cutoff of |log (fold change)| > 1, P value <0.05 by using package “limma” in R. Functional enrichment analysis was performed by DAVID, and the protein-protein interaction network of intersected DEGs between stromal score and immune score groups was conducted using the STRING database. The Kaplan–Meier method was used to explore DEGs with predictive values in overall survival, and the prognostic DEGs were further validated in a Gene Expression Omnibus (GEO) dataset GSE29609. Results A higher immune score was associated with T3/4 (vs. T1/2, P < 0.001), N1 (vs. N0, P=0.05), M1 (vs. M0, P=0.004), G3/4 (vs. G1/2, P < 0.001), advanced AJCC stage (P < 0.001), and shorter overall survival (P=0.04). Intersected DEGs between immune and stromal score groups were 48 upregulated and 47 downregulated genes, with 43 DEGs associated with overall survival in ccRCC. After validation by a cohort of 39 ccRCC cases with detailed follow-up information from GSE29609, six immune-associated DEGs including CASP5, HSD11B1, VSIG4, HMGCS2, HSD11B2, and OGDHL were demonstrated to be predictive of prognosis in ccRCC. Conclusions Our study elucidated tight associations between immune score and clinical characteristics as well as prognosis in ccRCC. Moreover, six DEGs were explored and validated to exert predictive values in overall survival of ccRCC.

Background lncRNAs have been proved to play crucial parts in various human cytopathology and cell physiology, including tumorigenesis. Down-regulated lncRNAs SNHG6 have shown great cell proliferation inhibitory effects in cancer development. Here we investigated how SNHG6 effected human osteosarcoma (OS) development and progression. Methods: Reverse transcription-quantitative PCR was performed to detect SNHG6 mRNA level in both OS tissues and cell lines. MTT and colony formation assays were used to determine the growth impact of SNHG6. Wound healing and trans-well assay were performed to measure the invasion effect of SNHG6. Western blotting were utilized to dissect molecular mechanisms. Results We identified SNHG6 as a lncRNAs that significantly up-regulated in OS tissues and cells, patients with high SNHG6 expression suffered more malignant metastasis and shorter survival times. Furthermore, silencing of SNHG6 in OS significantly inhibited OS cell growth, weakened cell invasion capacity, arrested cell cycle at G0/G1 phase, and induced cell apoptosis. Additionally, mechanism assays suggested that SNHG6 could competitively sponging miR-26a-5p thereby regulating ULK1, and induced cell apoptosis and autophagy by targeting caspase3 and ATF3. Conclusions: Our findings demonstrated that SNHG6 acted as an oncogene in osteosarcoma cells through regulating miR-26a-5p/ULK1 at a post-transcriptional level. SNHG6 might serve as a candidate prognostic biomarker and a target for novel therapies of osteosarcoma patients.

Background: Different proportions of Gleason pattern 3 and Gleason pattern 4 lead to various prognosis of prostate cancer with Gleason score 7. The objective of this study was to compare the survival outcomes of Gleason score 3+4 and 4+3 based on data from the Surveillance, Epidemiology, and End Results cancer registry database, and to investigate independent prognosis-associated factors and develop nomograms for predicting survival in Gleason score 7 prostate cancer patients. Methods: A retrospective study was conducted on 69,116 cases diagnosed as prostate adenocarcinoma with Gleason score 7 between 2004 and 2009. Prognosis-associated factors were evaluated using univariate and multivariate Cox regression analysis, and a 1:1 ratio paired cohort by propensity score matching with the statistical software IBM SPSS, to evaluate prognostic differences between Gleason score 3+4 and 4+3. The primary cohort was randomly divided into training set ( n = 48,384) and validation set ( n = 20,732). Based on the independent factors of prognosis, nomograms for prognosis were established by the training group and validated by the validation group using R version 3.5.0. Results: After propensity score matching, Cox regression analysis showed that Gleason 4+3 had an increased mortality risk both for overall survival (HR: 1.235, 95% CI: 1.179–1.294, P < 0.001) and cancer-specific survival (HR: 1.606, 95% CI: 1.468–1.762, P < 0.001). Nomograms for overall survival and cancer-specific survival were established with C-index 0.786 and 0.842, respectively. The calibration plot indicated an optimal agreement between the actual observation and nomogram prediction for overall survival and cancer-specific survival probability at 5 or 10 year. Conclusions: Prostate cancer with Gleason score 4+3 had worse overall survival and cancer-specific survival than Gleason score 3+4. Nomograms were formulated to predict 5-year and 10-year OS and CSS in patients with prostate cancer of Gleason score 7.