Enhanced Oxidative Phosphorylation Driven by TACO1 Mitochondrial Translocation Promotes Stemness and Cisplatin Resistance in Bladder Cancer.

Chemoresistance poses a critical obstacle in bladder cancer (BCa) treatment, and effective interventions are currently limited. Elevated oxidative phosphorylation (OXPHOS) has been linked to cancer stemness, a determinant of chemoresistance. However, the mechanisms underlying increased OXPHOS during cancer cell chemoresistance remain unclear.

Safety and Efficacy of Second-Line TKI Plus Anti-PD1 in Metastatic Non-Clear Cell Renal Cell Carcinoma: A Real-World Study.

Objectives: Guidelines recommend clinical trials or tyrosine kinase inhibitor (TKI) as the first-line option for systemic therapy for non-clear cell renal cell carcinoma (nccRCC) with limited efficacy. However, the preferred subsequent options remain unclear when patients progress after first-line treatment. This study aimed to evaluate the efficacy and safety of anti-PD-1 plus TKI therapy as the second-line regimen in nccRCC.

Long-term effect of acute ischemic injury on the kidney underwent clamped partial nephrectomy.

GFR reaches a new baseline, primarily correlating with nephron-mass preservation, 1-12 months after partial nephrectomy (PN). However, does the ipsilateral GFR experience subsequent decline, and does acute ischemic injury has long-term effect on the operated kidney? 319 patients with two kidneys and unilateral clamped PN were analyzed. All had preoperative, new-baseline, and latest follow-up imaging/serum creatinine levels.

mC-dependent cross-regulation between nuclear reader ALYREF and writer NSUN2 promotes urothelial bladder cancer malignancy through facilitating RABL6/TK1 mRNAs splicing and stabilization.

The significance of 5-methylcytosine (mC) methylation in human malignancies has become an increasing focus of investigation. Here, we show that mC regulators including writers, readers and erasers, are predominantly upregulated in urothelial carcinoma of the bladder (UCB) derived from Sun Yat-sen University Cancer Center and The Cancer Genome Atlas cohort. In addition, NOP2/Sun RNA methyltransferase family member 2 (NSUN2) as a methyltransferase and Aly/REF export factor (ALYREF) as a nuclear mC reader, are frequently coexpressed in UCB.

Targeting treatment of bladder cancer using PTK7 aptamer-gemcitabine conjugate.

Background: Gemcitabine (GEM) is one of the first-line chemotherapies for bladder cancer (BC), but the GEMs cannot recognize cancer cells and have a low long-term response rate and high recurrence rate with side effects during the treatment of BC. Targeted transport of GEMs to mediate cytotoxicity to tumor and avoid the systemic side effects remains a challenge in the treatment of BC.

Methods: Based on a firstly confirmed biomarker in BC-protein tyrosine kinase 7 (PTK7), which is overexpressed on the cell membrane surface in BC cells, a novel targeting system protein tyrosine kinase 7 aptamer-Gemcitabine conjugate (PTK7-GEMs) was designed and synthesized using a specific PTK7 aptamer and GEM through auto-synthesis method to deliver GEM against BC.

Genomic Characteristics and Single-Cell Profiles After Immunotherapy in Fumarate Hydratase-Deficient Renal Cell Carcinoma.

Purpose: Fumarate hydratase-deficient renal cell carcinoma (FHRCC) is highly malignant, but the urgent need for effective treatment remains unmet. We aimed to analyze the genomic characteristics and microenvironment of FHRCC and the cause of heterogeneous response to immune checkpoint inhibitor (ICI)-based treatment at single-cell level.

Experimental Design: Whole-exome sequencing and IHC staining analyses were performed in 30 advanced FHRCC patients.

Role of Sam68 in Sunitinib induced renal cell carcinoma apoptosis.

Sunitinib is one of the first-line targeted drugs for metastatic renal cell carcinoma (RCC) with dual effects of antiangiogensis and proapoptosis. Sam68 (Src-associated in mitosis, 68 KDa), is found being involved in cell apoptosis. This article reveals that Sam68 impacts the sensitivity to sunitinib by mediating the apoptosis of RCC cells.

FXR1 can bind with the CFIm25/CFIm68 complex and promote the progression of urothelial carcinoma of the bladder by stabilizing TRAF1 mRNA.

RNA-binding proteins (RBPs) are key regulators of gene expression. RBP dysregulation is reported to play essential roles in tumorigenesis. However, the role of RBPs in urothelial carcinoma of the bladder (UCB) is only starting to be unveiled.

Treatment of bladder cancer by geoinspired synthetic chrysotile nanocarrier-delivered circPRMT5 siRNA.

Background: Circular RNAs (circRNAs) have important functions in many fields of cancer biology. In particular, we previously reported that the oncogenic circRNA, circPRMT5, has a major role in bladder cancer progression. Therapy based on circRNAs have good prospects as anticancer strategies.

Single-cell transcriptomics reveals a low CD8 T cell infiltrating state mediated by fibroblasts in recurrent renal cell carcinoma.

Purpose: Recurrent renal cell carcinoma(reRCC) is associated with poor prognosis and the underlying mechanism is not yet clear. A comprehensive understanding of tumor microenvironment (TME) of reRCC may aid in designing effective anticancer therapies, including immunotherapies. Single-cell transcriptomics holds great promise for investigating the TME, however, this technique has not been used in reRCC.

LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis.

Reactive oxygen species (ROS) which are continuously generated mainly by mitochondria, have been proved to play an important role in the stress signaling of cancer cells. Moreover, pentatricopeptide repeat (PPR) proteins have been suggested to take part in mitochondrial metabolism. However, the mechanisms integrating the actions of these distinct networks in urothelial carcinoma of the bladder (UCB) pathogenesis are elusive.

Long noncoding RNAs to predict postoperative recurrence in bladder cancer and to develop a new molecular classification system.

Background: Reliable molecular markers are much needed for early prediction of recurrence in muscle-invasive bladder cancer (MIBC) patients. We aimed to build a long-noncoding RNA (lncRNA) signature to improve recurrence prediction and lncRNA-based molecular classification of MIBC.

Methods: LncRNAs of 320 MIBC patients from the Cancer Genome Atlas (TCGA) database were analyzed, and a nomogram was established.

Stereotactic body radiotherapy in combination with non-frontline PD-1 inhibitors and targeted agents in metastatic renal cell carcinoma.

Background: Radiotherapy may work synergistically with immunotherapy and targeted agents. We aimed to assess the safety and outcomes of stereotactic body radiotherapy (SBRT) plus non-first-line programmed death-1 (PD-1) inhibitors and targeted agents (TA) in metastatic renal cell carcinoma (mRCC).

Methods: We retrospectively reviewed 74 patients treated with non-first-line PD-1 inhibitors plus TA in non-first-line setting.

ZHX3 promotes the progression of urothelial carcinoma of the bladder via repressing of RGS2 and is a novel substrate of TRIM21.

Clinically, patients with urothelial carcinoma of the bladder (UCB) with tumor metastasis are incurable. To find new therapeutic strategies, the mechanisms underlying UCB invasion and metastasis should be further investigated. In this study, zinc finger and homeobox 3 (ZHX3) was first screened as a critical oncogenic factor associated with poor prognosis in a UCB dataset from The Cancer Genome Atlas (TCGA).

Prognostic significance of tumor-infiltrating immune cells in muscle-invasive bladder cancer.

Background: Muscle-invasive bladder cancer (MIBC) is a lethal disease with poor treatment response and a high death rate. Immune cells infiltrating the tumor tissues have been shown to play a vital role in tumorigenesis and tumor progression, but their prognostic significance in MIBC remains unclear.

Objectives: To explore the landscape and prognostic significance of tumor-infiltrating immune cells (TIICs) in MIBC, and to develop a model to improve the prognostic predictions of MIBC.

5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs.

Although 5-methylcytosine (mC) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the single-nucleotide resolution landscape of messenger RNA mC modifications in human urothelial carcinoma of the bladder (UCB). We identify numerous oncogene RNAs with hypermethylated mC sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an mC 'reader' recognizing mC-modified mRNAs through the indole ring of W65 in its cold-shock domain.

Kinesin family member C1 accelerates bladder cancer cell proliferation and induces epithelial-mesenchymal transition via Akt/GSK3β signaling.

Kinesin family member C1 (KIFC1) is implicated in the clustering of multiple centrosomes to maintain tumor survival and is thought to be an oncogene in several kinds of cancers. In our experiments, we first performed bioinformatics analysis to investigate the expression levels of KIFC1 in bladder cancer (BC) specimens and normal bladder epitheliums and then, using our samples, verified findings by quantitative real-time PCR and western blotting assays. All data showed that KIFC1 was significantly upregulated in BC specimens at both the mRNA and protein levels.

Overexpression of CEP72 Promotes Bladder Urothelial Carcinoma Cell Aggressiveness via Epigenetic CREB-Mediated Induction of SERPINE1.

A vital constituent of the centrosome involved in regulating the activity of the organelle during the cell cycle is centrosomal protein (CEP)-72, whose function in the case of human cancer yet lacks clarity. The expression dynamics of CEP72 and its clinical impact were examined in a large cohort of bladder tissues. Several experiments at both the in vitro and in vivo levels on urothelial carcinoma of the bladder (UCB) cells were conducted to understand the role of this molecule along with the mechanisms.

PRMT5 Circular RNA Promotes Metastasis of Urothelial Carcinoma of the Bladder through Sponging miR-30c to Induce Epithelial-Mesenchymal Transition.

Purpose: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in cancer cells epithelial-mesenchymal transition (EMT) remains unclear. In this study, we aimed to identify novel circRNAs that regulate urothelial carcinoma of the bladder (UCB) cells' EMT and explored their regulatory mechanisms and clinical significance in UCBs.

TRIM65 supports bladder urothelial carcinoma cell aggressiveness by promoting ANXA2 ubiquitination and degradation.

Clinically, most of human urothelial carcinoma of the bladder (UCB)-related deaths result from tumor metastasis, but the underlying molecular mechanisms are largely unknown. Recently, a growing number of tripartite motif (TRIM) family members have been suggested to be important regulators for tumorigenesis. However, the impact of most TRIM members on UCB pathogenesis is unclear.