VHL governs m6A modification and PIK3R3 mRNA stability in clear cell renal cell carcinomas
N6-Methyladenosine (m6A), a prevalent posttranscriptional modification, plays an important role in cancer progression. Clear cell renal cell carcinoma (ccRCC) is chiefly associated with the loss of the von Hippel-Lindau (VHL) gene, encoding a component of the E3 ubiquitin ligase complex. In this issue of the JCI, Zhang and colleagues unveiled a function of VHL beyond its canonical role as an E3 ubiquitin ligase in regulating hypoxia-inducible factors (HIFs). It also governed m6A modification by orchestrating the assembly of m6A writer proteins METTL3 and METTL14, thereby stabilizing PIK3R3 mRNA. Mechanistically, PIK3R3 con...
Source: Journal of Clinical Investigation - April 15, 2024 Category: Biomedical Science Authors: Hyemin Lee, Li Zhuang, Boyi Gan Source Type: research
Von Hippel Lindau tumor suppressor controls m6A-dependent gene expression in renal tumorigenesis
In this study, we demonstrate that VHL binds and promotes METTL3/METTL14 complex formation while VHL depletion suppresses m6A modification, which is distinctive from its canonical E3 ligase role. m6A RNA immunoprecipitation sequencing (RIP-Seq) coupled with RNA-Seq allows us to identify a selection of genes whose expression may be regulated by VHL-m6A signaling. Specifically, PIK3R3 is identified to be a critical gene whose mRNA stability is regulated by VHL in a m6A-dependent but HIF-independent manner. Functionally, PIK3R3 depletion promotes renal cancer cell growth and orthotopic tumor growth while its overexpression le...
Source: Journal of Clinical Investigation - April 15, 2024 Category: Biomedical Science Authors: Cheng Zhang, Miaomiao Yu, Austin J. Hepperla, Zhao Zhang, Rishi Raj, Hua Zhong, Jin Zhou, Lianxin Hu, Jun Fang, Hongyi Liu, Qian Liang, Liwei Jia, Chengheng Liao, Sichuan Xi, Jeremy M. Simon, Kexin Xu, Zhijie Liu, Yunsun Nam, Payal Kapur, Qing Zhang Source Type: research
VHL loss reprograms the immune landscape to promote an inflammatory myeloid microenvironment in renal tumorigenesis
Clear cell renal cell carcinoma (ccRCC) is characterized by dysregulated hypoxia signaling and a tumor microenvironment (TME) highly enriched in myeloid and lymphoid cells. Loss of the von Hippel Lindau (VHL) gene is a critical early event in ccRCC pathogenesis and promotes stabilization of HIF. Whether VHL loss in cancer cells affects immune cells in the TME remains unclear. Using Vhl WT and Vhl-KO in vivo murine kidney cancer Renca models, we found that Vhl-KO tumors were more infiltrated by immune cells. Tumor-associated macrophages (TAMs) from Vhl-deficient tumors demonstrated enhanced in vivo glucose consumption, phag...
Source: Journal of Clinical Investigation - April 15, 2024 Category: Biomedical Science Authors: Melissa M. Wolf, Matthew Z. Madden, Emily N. Arner, Jackie E. Bader, Xiang Ye, Logan Vlach, Megan L. Tigue, Madelyn D. Landis, Patrick B. Jonker, Zaid Hatem, KayLee K. Steiner, Dakim K. Gaines, Bradley I. Reinfeld, Emma S. Hathaway, Fuxue Xin, M. Noor Tan Source Type: research
Multi-omics and immunogenomics analysis revealed PFKFB3 as a targetable hallmark and mediates sunitinib resistance in papillary renal cell carcinoma: in silico study with laboratory verification
Eur J Med Res. 2024 Apr 15;29(1):236. doi: 10.1186/s40001-024-01808-5.ABSTRACTGlycolysis-related metabolic reprogramming is a central hallmark of human cancers, especially in renal cell carcinoma. However, the regulatory function of glycolytic signature in papillary RCC has not been well elucidated. In the present study, the glycolysis-immune predictive signature was constructed and validated using WGCNA, glycolysis-immune clustering analysis. PPI network of DEGs was constructed and visualized. Functional enrichments and patients' overall survival were analyzed. QRT-PCR experiments were performed to detect hub genes' expre...
Source: Cell Research - April 15, 2024 Category: Cytology Authors: Zhongwen Lu Yongsheng Pan Songbo Wang Jiajin Wu Chenkui Miao Zengjun Wang Source Type: research
zDHHC3-mediated S-palmitoylation of SLC9A2 regulates apoptosis in kidney clear cell carcinoma
CONCLUSION: Our findings suggest that zDHHC3 plays an important role in KIRC, due partly to its regulation of SLC9A2 S-palmitoylation. The targeting of the zDHHC3-SLC9A2 axis may provide a new option for the clinical treatment of KIRC.PMID:38619631 | DOI:10.1007/s00432-024-05737-y (Source: Cell Research)
Source: Cell Research - April 15, 2024 Category: Cytology Authors: Xiuyun Zhang Junpeng Hou Guangyuan Zhou Haixia Wang Zeang Wu Source Type: research
Multi-omics and immunogenomics analysis revealed PFKFB3 as a targetable hallmark and mediates sunitinib resistance in papillary renal cell carcinoma: in silico study with laboratory verification
AbstractGlycolysis-related metabolic reprogramming is a central hallmark of human cancers, especially in renal cell carcinoma. However, the regulatory function of glycolytic signature in papillary RCC has not been well elucidated. In the present study, the glycolysis-immune predictive signature was constructed and validated using WGCNA, glycolysis-immune clustering analysis. PPI network of DEGs was constructed and visualized. Functional enrichments and patients’ overall survival were analyzed. QRT-PCR experiments were performed to detect hub genes’ expression and distribution, siRNA technology was used to silenc e t...
Source: European Journal of Medical Research - April 15, 2024 Category: Research Source Type: research
zDHHC3-mediated S-palmitoylation of SLC9A2 regulates apoptosis in kidney clear cell carcinoma
ConclusionOur findings suggest that zDHHC3 plays an important role in KIRC, due partly to its regulation of SLC9A2 S-palmitoylation. The targeting of the zDHHC3 –SLC9A2 axis may provide a new option for the clinical treatment of KIRC. (Source: Journal of Cancer Research and Clinical Oncology)
Source: Journal of Cancer Research and Clinical Oncology - April 15, 2024 Category: Cancer & Oncology Source Type: research
Preliminary Investigation of a Rapid and Feasible Therapeutic Drug Monitoring Method for the Real-Time Estimation of Blood Pazopanib Concentrations
AbstractPazopanib is a multi-kinase inhibitor used to treat advanced/metastatic renal cell carcinoma and advanced soft tissue tumors; however, side effects such as diarrhea and hypertension have been reported, and dosage adjustment based on drug concentration in the blood is necessary. However, measuring pazopanib concentrations in blood using the existing methods is time-consuming; and current dosage adjustments are made using the results of blood samples taken at the patient's previous hospital visit (approximately a month prior). If the concentration of pazopanib could be measured during the waiting period for a doctor ...
Source: The AAPS Journal - April 15, 2024 Category: Drugs & Pharmacology Source Type: research
Familial syndromes associated with testicular and paratesticular neoplasms: a comprehensive review
AbstractA syndromic association between a subset of testicular/paratesticular neoplasms is well established. Such examples include Carney complex and large cell calcifying Sertoli cell tumor, Peutz-Jeghers syndrome and intratubular large cell hyalinizing Sertoli cell neoplasia, and VHL syndrome and clear cell papillary cystadenoma of the epididymis.However, recent studies proposed potential novel links between some testicular and paratesticular neoplasms with certain tumor syndromes. While more studies are still needed to solidify these associations, recent research suggests that a subset of Leydig cell tumors may arise in...
Source: Virchows Archiv - April 15, 2024 Category: Pathology Source Type: research
Hemangioblastoma: An Uncommon Cause of Polycythemia in a Child
We report a 13-year-old girl with primarily neurological symptoms identified to be polycythemic during routine evaluation. Clinical examination and neuroimaging subsequently confirmed an intracranial space occupying lesion which was excised. Hemoglobin level normalized after tumor excision. This case report emphasizes the need for thorough systemic evaluation including central nervous system examination in children identified to be polycythemic. Keywords: CNS tumor; hemangioblastoma; polycythemia.PMID:38615229 | DOI:10.33314/jnhrc.v21i3.4160 (Source: Cell Research)
Source: Cell Research - April 14, 2024 Category: Cytology Authors: Surabhi Aryal Arun Kumar Sharma Source Type: research
Cuproptosis: A potential therapeutic target in clear cell renal cell carcinoma
Chin Med J (Engl). 2024 Apr 12. doi: 10.1097/CM9.0000000000003076. Online ahead of print.NO ABSTRACTPMID:38613200 | DOI:10.1097/CM9.0000000000003076 (Source: Chinese Medical Journal)
Source: Chinese Medical Journal - April 13, 2024 Category: General Medicine Authors: Yuetong Zhao Jie Li Xiaojie Lu Shuang Wu Yunze Xing Yaxuan Fang Bo Yang Source Type: research
Cuproptosis: A potential therapeutic target in clear cell renal cell carcinoma
Chin Med J (Engl). 2024 Apr 12. doi: 10.1097/CM9.0000000000003076. Online ahead of print.NO ABSTRACTPMID:38613200 | DOI:10.1097/CM9.0000000000003076 (Source: Chinese Medical Journal)
Source: Chinese Medical Journal - April 13, 2024 Category: General Medicine Authors: Yuetong Zhao Jie Li Xiaojie Lu Shuang Wu Yunze Xing Yaxuan Fang Bo Yang Source Type: research
Wide-Targeted Semi-Quantitative Analysis of Acidic Glycosphingolipids in Cell Lines and Urine to Develop Potential Screening Biomarkers for Renal Cell Carcinoma
In conclusion, urinary DSGb5 (d18:1/16:0) was a potential biomarker for cancer screening, which could contribute to the treatment of RCC patients.PMID:38612906 | DOI:10.3390/ijms25074098 (Source: Cancer Control)
Source: Cancer Control - April 13, 2024 Category: Cancer & Oncology Authors: Masamitsu Maekawa Tomonori Sato Chika Kanno Izumi Sakamoto Yoshihide Kawasaki Akihiro Ito Nariyasu Mano Source Type: research
Combination immune checkpoint and targeted protein kinase inhibitors for the treatment of renal cell carcinomas
Pharmacol Res. 2024 Apr 11:107181. doi: 10.1016/j.phrs.2024.107181. Online ahead of print.ABSTRACTKidney cancers comprise about 3% of all new malignancies in the United States. Renal cell carcinomas (RCCs) are the most common type of renal malignancy making up about 85% of kidney cancer cases. Signs and symptoms of renal cell carcinomas can result from local tumor growth, paraneoplastic syndromes, or distant metastases. The classic triad of presentation with flank pain, hematuria, and a palpable abdominal mass occurs in fewer than 10% of patients. Most diagnoses result from incidental imaging findings (ultrasonography or a...
Source: Cell Research - April 13, 2024 Category: Cytology Authors: Robert Roskoski Source Type: research
PSAT1 enhances the efficacy of the prognosis estimation nomogram model in stage-based clear cell renal cell carcinoma
Clear cell renal cell carcinoma (ccRCC) is associated with a high prevalence of cancer-related deaths. The survival rates of patients are significantly lower in late-stage ccRCC than in early-stage ccRCC, due ... (Source: BMC Cancer)
Source: BMC Cancer - April 13, 2024 Category: Cancer & Oncology Authors: Jun Wang, Xiaoming He, Yuanyuan Mi, Yong Q. Chen, Jie Li and Rong Wang Tags: Research Source Type: research
