Determinants and Dynamic Changes of Generic Quality of Life in Human Bladder Cancer Patients

We measured and determined the factors associated with long-term generic quality-of-life (QOL) changes in human bladder cancer patients. We utilized the World Health Organization QOL-Brief questionnaire to assess consecutive patients’ QOL at outpatient clinics of our hospital. A mixed-effects model was constructed to investigate the determinants of QOL changes according to each domain and individual item after controlling for demographic and clinical factors, as well as the effect of radical cystectomy. We also applied a kernel smoothing method to describe the long-term dynamic changes after the first definite treatment. In total, 1185 repeated measurements were collected from 343 bladder cancer patients. The mixed-effects models demonstrated that marital status, monthly income, and comorbidity with heart disease and diabetes were significant determinants among all the study participants. Regardless of the urinary diversion type, radical cystectomy contributed to lower scores for all four domains, mainly from 4–5 years after cystectomy, which declined significantly in patients who were older than 60 years. As for non-muscle-invasive bladder cancer (NMIBC) patients with preserved bladders, tumor recurrence was a major predictor for lower scores for sexual activity in the social domain. In summary, generic QOL can be independently influenced by many factors, not only cystectomy and tumor recurrence, which should be discussed with patients before treatment.

circKDM4C enhances bladder cancer invasion and metastasis through miR-200bc-3p/ZEB1 axis

Circular RNAs (circRNAs) play essential roles in human bladder cancer (BCa) development, however, unusual expression patterns and functional dysfunction of circRNAs in BCa have not been evaluated. In this study, we validated that circKDM4C (hsa_circ_0001839), derived from the KDM4C gene, is elevated in BCa cell lines as well as tissues. Functionally, overexpression of circKDM4C significantly enhances, and silencing of circKDM4C suppresses migration and invasion capabilities of BCa cells. Mechanistically, circKDM4C can directly interact with miR-200b-3p and miR-200c-3p as a miRNA sponge, which enhances the expression of ZEB1 and promotes mesenchymal phenotype. Conclusively, our findings indicate that circKDM4C may act as a pro-oncogenic factor in BCa invasion and metastasis via the circKDM4C/miR-200bc-3p/ZEB1 axis, which is a potential biomarker or therapeutic target for bladder cancer.

Transcriptome-Wide Map of N6-Methyladenosine Methylome Profiling in Human Bladder Cancer

N6-Methyladenosine (m6A) is the most widespread internal RNA modification in several species. In spite of latest advances in researching the biological roles of m6A, its function in the development and progression of bladder cancer remains unclear. In this study, we used MeRIPty -55-seq and RNA-seq methods to obtain a comprehensive transcriptome-wide m6A profiling and gene expression pattern in bladder cancer and paired normal adjacent tissues. Our findings showed that there were 2,331 hypomethylated and 3,819 hypermethylated mRNAs, 32 hypomethylated and 105 hypermethylated lncRNAs, and 15 hypomethylated and 238 hypermethylated circRNAs in bladder cancer tissues compared to adjacent normal tissues. Furthermore, m6A is most often harbored in the coding sequence (CDS), with some near the start and stop codons between two groups. Functional enrichment analysis revealed that differentially methylated mRNAs, lncRNAs, and circRNAs were mostly enriched in transcriptional misregulation in cancer and TNF signaling pathway. We also found that different m6A methylation levels of gene might regulate its expression. In summary, our results for the first time provide an m6A landscape of human bladder cancer, which expand the understanding of m6A modifications and uncover the regulation of mRNAs, lncRNAs, and circRNAs through m6A modification in bladder cancer.