N6-methyladenosine-modified circRPS6KC1 regulated cellular senescence in prostate cancer via FOXM1/PCNA axis.

Prostate cancer (PCa) gradually becomes the most common cancer in men in many countries, of which circRNAs and methylated modification exert an essential role in PCa progression. However, the concrete mechanisms of N6-methyladenosine (m6A) modification of circRNAs in PCa remain unclear. In our study, we identified circRPS6KC1, a novel and up-regulated circular RNA in PCa, through circRNA sequencing.

Co-transcriptional R-loops-mediated epigenetic regulation drives growth retardation and docetaxel chemosensitivity enhancement in advanced prostate cancer.

R-loops are prevalent three-stranded nucleic acid structures, comprising a DNA-RNA hybrid and a displaced single-stranded DNA, that frequently form during transcription and may be attributed to genomic stability and gene expression regulation. It was recently discovered that RNA modification contributes to maintain the stability of R-loops such as N6-methyladenosine (mA). Yet, mA-modified R-loops in regulating gene transcription remains poorly understood.

N6-methyladenosine-modified CircPSMA7 enhances bladder cancer malignancy through the miR-128-3p/MAPK1 axis.

Several studies have indicated that circular RNAs (circRNAs) play vital roles in the progression of various diseases, including bladder cancer (BCa). However, the underlying mechanisms by which circRNAs drive BCa malignancy remain unclear. In this study, we identified a novel circRNA, circPSMA7 (circbaseID:has_circ_0003456), showing increased expression in BCa cell lines and tissues, by integrating the reported information with circRNA-seq and qRT-PCR.

FTO promotes clear cell renal cell carcinoma progression via upregulation of PDK1 through an mA dependent pathway.

FTO, as an mA mRNA demethylase, is involved in various cancers. However, the role of FTO in clear cell renal cell carcinoma (ccRCC) remains unclear. In the present study, we discovered FTO is upregulated in ccRCC.

SMAD3 and FTO are involved in miR-5581-3p-mediated inhibition of cell migration and proliferation in bladder cancer.

Previous research evidence suggests that microRNAs (miRNAs) play an indispensable role in onset and progression of bladder cancer (BCa). Here, we explored the functions and mechanisms of miR-5581-3p in BCa. miR-5581-3p, as a tumor suppressor in BCa, was detected at a lower expression level in BCa tissue and cells in contrast with the non-malignant bladder tissue and cells.

Diverse Roles and Therapeutic Potentials of Circular RNAs in Urological Cancers.

Circular RNAs (circRNAs) are a novel class of noncoding RNAs, which are mainly formed as a loop structure at the exons caused by noncanonical splicing; they are much more stable than linear transcripts; recent reports have suggested that the dysregulation of circRNAs is associated with the occurrence and development of diseases, especially various human malignancies. Emerging evidence demonstrated that a large number of circRNAs play a vital role in a series of biological processes such as tumor cell proliferation, migration, drug resistance, and immune escape. Additionally, circRNAs were also reported to be potential prognostic and diagnostic biomarkers in cancers.

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.

The Regulatory Role of RNA Metabolism Regulator TDP-43 in Human Cancer.

TAR-DNA-binding protein-43 (TDP-43) is a member of hnRNP family and acts as both RNA and DNA binding regulator, mediating RNA metabolism and transcription regulation in various diseases. Currently, emerging evidence gradually elucidates the crucial role of TDP-43 in human cancers like it is previously widely researched in neurodegeneration diseases. A series of RNA metabolism events, including mRNA alternative splicing, transport, stability, miRNA processing, and ncRNA regulation, are all confirmed to be closely involved in various carcinogenesis and tumor progressions, which are all partially regulated and interacted by TDP-43.

MicroRNA-501-3p inhibits the proliferation of kidney cancer cells by targeting WTAP.

Background: Emerging evidence suggests that miR-501-3p plays an important role in the pathogenesis and progression of various carcinomas. However, its role and underlying mechanisms in renal cell carcinoma (RCC) remain to be elucidated.

Methods: Quantitative RT-PCR, western blot, and bioinformatics methods were used to evaluate the expression of miR-501-3p and Wilms' tumor 1-associating protein (WTAP) in RCC cell lines and clinical tissues.

EGR2-mediated regulation of mA reader IGF2BP proteins drive RCC tumorigenesis and metastasis via enhancing S1PR3 mRNA stabilization.

Emerging discoveries of dynamic and reversible N6-methyladenosine (mA) modification on RNA in mammals have revealed the key roles of the modification in human tumorigenesis. As known mA readers, insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) are upregulated in most cancers and mediates the enhancement of mA-modified mRNAs stability. However, the mechanisms of IGF2BPs in renal cell cancer (RCC) still remain unclear.

Comprehensive Analysis of Ferroptosis Regulators With Regard to PD-L1 and Immune Infiltration in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the tumor types with sensitivity to ferroptosis, and immunotherapy has emerged as a standard pillar for metastatic ccRCC treatment, while it remains largely obscure whether ferroptosis influences the tumor immune microenvironment in ccRCC. Based on available data in The Cancer Genome Atlas, divergent expression profiles of ferroptosis regulators were noted in ccRCC and normal tissues, and we also found that the ferroptosis regulators correlated with the PD-L1 expression. Two independent subtypes were determined by consensus clustering analysis according to the expression level of ferroptosis regulators in ccRCC.

Upregulation of ARNTL2 is associated with poor survival and immune infiltration in clear cell renal cell carcinoma.

Background: Aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2) is a member of the PAS superfamily. Previous studies explored the carcinogenic roles of transcription factor ARNTL2 in human malignancies. However, its roles in ccRCC have not been elucidated.

miR-665 inhibits epithelial-to-mesenchymal transition in bladder cancer via the SMAD3/SNAIL axis.

Emerging research indicates that miRNAs can regulate cancer progression by influencing molecular pathways. Here, we studied miR-665, part of the DLK1-DIO3 miRNA cluster, which is downregulated by upstream methylation in bladder cancer. MiR-665 overexpression significantly downregulated the expression of SMAD3, phospho-SMAD3, and SNAIL, reversed epithelial-mesenchymal transition progression, and inhibited the migration of bladder cancer cells.

Prognostic Value of Tumor-Associated Macrophages in Clear Cell Renal Cell Carcinoma: A Systematic Review and Meta-Analysis.

Background: Tumor-associated macrophages (TAMs) are the major immune cells in tumor microenvironment. The prognostic significance of TAMs has been confirmed in various tumors. However, whether TAMs can be prognostic factors in clear cell renal cell carcinoma (ccRCC) is unclear.

YTHDF2 mediates the mRNA degradation of the tumor suppressors to induce AKT phosphorylation in N6-methyladenosine-dependent way in prostate cancer.

Background: N6-methyladenosine (mA) is the most abundant modification in mRNA of humans. Emerging evidence has supported the fact that mA is comprehensively involved in various diseases especially cancers. As a crucial reader, YTHDF2 usually mediates the degradation of mA-modified mRNAs in mA-dependent way.

Roles of N -methyladenosine (m A) RNA modifications in urological cancers.

Epigenetics has long been a hot topic in the field of scientific research. The scope of epigenetics usually includes chromatin remodelling, DNA methylation, histone modifications, non-coding RNAs and RNA modifications. In recent years, RNA modifications have emerged as important regulators in a variety of physiological processes and in disease progression, especially in human cancers.

METTL3/YTHDF2 m A axis promotes tumorigenesis by degrading SETD7 and KLF4 mRNAs in bladder cancer.

N6-Methyladenosine (m A) modification, the most prevalent modification of eukaryotic messenger RNA (mRNA), is involved in the progression of various tumours. However, the specific role of m A in bladder cancer (BCa) is still poorly understood. In this study, we demonstrated the tumour-promoting function and specific regulatory mechanism of m A axis, consisting of the core 'writer' protein METTL3 and the major reader protein YTHDF2.

Lower circulating adiponectin is associated with higher risk of renal cell carcinoma: A meta-analysis.

Background: Changes in circulating adiponectin have been related to the risks of various cancers. However, the association between circulating adiponectin and the risk of renal cell carcinoma has not been fully determined. A meta-analysis was performed to evaluate the relationship between circulating adiponectin and renal cell carcinoma risk.

CCND1, NOP14 and DNMT3B are involved in miR-502-5p-mediated inhibition of cell migration and proliferation in bladder cancer.

Objectives: Downregulation of miR-502-5p has emerged as a critical factor in tumour progression in several cancers. Herein, we elucidated the role of miR-502-5p in bladder cancer.

Materials And Methods: RT-qPCR was performed to examine the expression of miR-502-5p in bladder cancer.

Dysregulation of ncRNAs located at the DLK1‑DIO3 imprinted domain: involvement in urological cancers.

Genomic imprinting has been found to be involved in human physical development and several diseases. The imprinted domain is located on human chromosome 14 and contains paternally expressed protein-coding genes () and numerous maternally expressed ncRNA genes (, , miRNAs, piRNAs, and snoRNAs). Emerging evidence has implicated that dysregulation of the imprinted domain especially the imprinted ncRNAs is critical for tumor progressions.

MIR-300 in the imprinted DLK1-DIO3 domain suppresses the migration of bladder cancer by regulating the SP1/MMP9 pathway.

Emerging research has suggested that miRNAs play a significant role in oncogenesis and tumor progression by regulating multiple molecular pathways. Here, we investigated miR-300, which inhibited bladder cancer (BCa) migration by regulating the SP1/MMP9 pathway. miR-300, belonging to the DLK1-DIO3 miRNA cluster, is frequently expressed at lower levels in BCa tissue than in adjacent normal tissue due to DNA methylation.

Secondhand smoking increases bladder cancer risk in nonsmoking population: a meta-analysis.

Background: Tobacco smoking has been widely acknowledged to be the most important risk factor for bladder cancer. However, whether secondhand smoking (SHS) increases the risk of bladder cancer still remains uncertain. We conducted a meta-analysis about the risk of bladder cancer and lifetime SHS and childhood SHS.

Dual regulatory role of CCNA2 in modulating CDK6 and MET-mediated cell-cycle pathway and EMT progression is blocked by miR-381-3p in bladder cancer.

Emerging evidence has elucidated that microRNAs (miRNAs) transcribed from miRNA cluster at DLK-DIO3 imprinted domain are involved in various cancers. However, as one member of this cluster, the underlying mechanisms and functions of miR-381-3p in bladder cancer (BCa) still remains elusive. Here we demonstrate that the hypermethylated status of upstream maternally expressed gene 3 divergent methylation region reduces the expression of miR-381-3p in BCa by bisulfite-sequencing PCR.

The dual role of N6-methyladenosine modification of RNAs is involved in human cancers.

As the most abundant and reversible RNA modification in eukaryotic cells, m A triggers a new layer of epi-transcription. M A modification occurs through a methylation process modified by "writers" complexes, reversed by "erasers", and exerts its role depending on various "readers". Emerging evidence shows that there is a strong association between m A and human diseases, especially cancers.

Pioglitazone use in patients with diabetes and risk of bladder cancer: a systematic review and meta-analysis.

Pioglitazone has been reported to increase the risk of bladder cancer but the conclusions of published clinical studies are confusing. We conducted a systematic review and meta-analysis of all eligible randomized controlled trial (RCT) studies and observational studies, in order to identify a more precise relationship between pioglitazone and risk of bladder cancer. We searched for publications up to January 24, 2018, in PubMed, EMBASE, Scopus, Web of Science, Cochrane register, and Chinese National Knowledge Infrastructure databases, and the references of the retrieved articles and relevant reviews were also checked.