miR-34a is downregulated and a regulator of drug resistance in prostate cancer (PCa). However, the mechanism of miR-34a in chemoresistance of PCa remains largely unknown. In the present study, we first confirmed the hypermethylation‑induced downregulation of miR-34a in PCa tissues and cell lines, PC-3 and DU145. Additionally, transfection of miR-34a mimics and demethylation by 5-azacytidine both resulted in the upregulation of miR-34a expression, which further induced declined cell proliferation and the enhanced apoptosis in PCa cells. Upregulation of miR-34a enhanced the chemosensitivity of PC-3 and DU145 cells. Furthermore, overexpression of miR-34a reduced the expression of autophagy-related proteins, ATG4B, Beclin-1 and LC3B II/I in PCa cells and demethylation treatment showed similar effect. ATG4B was confirmed directly by miR-34a targeting in PCa. Finally, downregulated p-AMPK and upregulated p-mTOR were detected in miR-34a overexpressed PCa cells. Collectively, miR-34a enhances chemosensitivity by directly downregulating ATG4B-induced autophagy through AMPK/mTOR pathway in PCa.

The aberrant expression of microRNAs (miRNAs/miRs) has been found in numerous cancer types. miR-32 is an oncomiR in prostate cancer (PCa), however, the mechanisms by which miR-32 functions as a regulator of radiotherapy response and resistance in PCa are largely unknown. In the present study, it was found that DAB2 interacting protein (DAB2IP), the miR-32-dependent tumor-suppressor gene, was downregulated and induced autophagy and inhibited radiotherapy-induced apoptosis in PCa cells. miR-32 expression was upregulated or overexpressed in PCa, and miR-32 inhibited DAB2IP expression through a direct binding site within the DAB2IP 3′ untranslated region. miR-32 mimics enhanced tumor cell survival and decreased radiosensitivity in the PCa cells, which were reversed by miR-32 inhibitor. Flow cytometric analysis revealed that overexpressed miR-32, consistent with the DAB2IP-knockdown results, reduced ionizing radiation (IR)-induced cell apoptosis, which was restored by 4 nM brefeldin A treatment. More significantly, the overexpression of miR-32 and the knockdown of DAB2IP enhanced autophagy in the IR-treated PCa cells. miR-32 regulated the expression of autophagy-related proteins, such as DAB2IP, Beclin 1 and Light chain 3β I/II, as well as phosphorylation of S6 kinase and mammalian target of rapamycin. In conclusion, these data provide novel insights into the mechanisms governing the regulation of DAB2IP expression by miR-32 and their possible contribution to autophagy and radioresistance in PCa.

The incidence of bladder cancer in traditional green tea‐consuming countries was dramatically lower than low green tea‐consuming countries. Epigallocatechin‐3‐gallate (EGCG), an active ingredient extracted from green tea, showed effective inhibition of formation and progression of many tumors. However, whether autophagy involved in this tumor‐suppression mechanism of EGCG on bladder cancer was still unclear. In this study, we demonstrated low concentration of EGCG‐induced proliferation inhibition and increased apoptosis in bladder cancer cell lines (5,637 and T24 cells) indicated by the increased expression of apoptosis‐related protein (caspase9, caspase3 and BAX). In addition, low dose of EGCG also regulated autophagy pathway associated protein (LC3B II and Beclin) expression and this autophagy pathway was blocked by PI3K/AKT inhibitor; moreover, knockdown of ATG5 reversed EGCG‐induced apoptosis in 5,637 cells, indicating that EGCG might inhibit the bladder cancer through autophagy pathway. Our findings indicated that EGCG should be considered as a novel therapy for bladder cancer treatment by regulating autophagy pathway. Practical applications Our research proved EGCG from green tea could be used as an effective anti‐tumor ingredient by revealing another mechanism that epigallocatechin‐3‐Gallate inhibited bladder cancer cells via inducing autophagy‐related apoptosis. And green tea could be considered as a kind of tumor‐preventing beverage.

Background. Most recently, no efficient prognostic indictor is present for kidney cancer. Thus, we aimed to build and validate a new prognostic gene signature for renal cancer patients using the Cancer Genomic Atlas (TCGA). Methods. A “time-dependent receiver operating characteristic (tROC)” curve was generated, and a log-rank test was performed to assess the performance of the biomarker in training and validation. A “ferroptosis-related gene signature” was developed. In different training and validations sets, tROC and log-rank test were used to validate the biomarker’s performance. Results. In the training set with a P value less than 0.01 and the validation set, the “gene signature” was significantly correlated with survival. Eventually, it was found that the ferroptosis-related gene signature was directly correlated with immune score and the score of tumor mutation, suggesting its role in predicting response to immunotherapy. Conclusion. We developed and validated a “ferroptosis-related gene signature” that can be sued for patients with kidney cancer. It can also assist in facilitating the plan for treatment and risk stratification.

Continuous monitoring for immunosuppressive status, infection and complications are a must for kidney transplantation (KTx) recipients. Traditional monitoring including blood sampling and kidney biopsy, which caused tremendous medical cost and trauma. Therefore, a cheaper and less invasive approach was urgently needed. We thought that a breath test has the potential to become a feasible tool for KTx monitoring. A prospective-specimen collection, retrospective-blinded assessment strategy was used in this study. Exhaled breath samples from 175 KTx recipients were collected in West China Hospital and tested by online ultraviolet photoionization time-of-flight mass spectrometry (UVP-TOF–MS). The classification models based on breath test performed well in classifying normal and abnormal values of creatinine, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN) and tacrolimus, with AUC values of 0.889, 0.850, 0.849 and 0.889, respectively. Regression analysis also demonstrated the predictive ability of breath test for clinical creatinine, eGFR, BUN, tacrolimus level, as the predicted values obtained from the regression model correlated well with the clinical true values (p < 0.05). The findings of this investigation implied that a breath test by using UVP-TOF–MS for KTx recipient monitoring is possible and accurate, which might be useful for future clinical screenings.