Use of Circular RNAs in Diagnosis, Prognosis and Therapeutics of Renal Cell Carcinoma

Osca-Verdegal, Rebeca; Beltrán-García, Jesús; Górriz, José Luis; Jabaloyas, J.M. Martínez; Pallardó, Federico V.; García‐Giménez, José Luis

doi:10.3389/fcell.2022.879814

Cited by 5 publications

(5 citation statements)

References 136 publications

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“…Currently, the detailed molecular mechanisms of these two RCC subtypes, in terms of occurrence and development, are not yet fully understood, although the application of proteomics and multi-omics approach to tissues, cultured cells, and biological fluids has provided significant advancement in RCC prognostic significance assessment [7][8][9][10][11] RCC tumorigenesis is a complex process involving genetic and epigenetic alterations. However, only a few types of RCCs can be explained by genetic predisposition, and epigenetic alterations in RCC subtypes are still poorly understood [12]. Therefore, understanding the roles of epigenetic modifications and underlying mechanisms in RCC could improve its diagnosis and clinical management.…”

Section: Introductionmentioning

confidence: 99%

“…RCC tumorigenesis is a complex process involving genetic and epigenetic alterations. However, only a few types of RCCs can be explained by genetic predisposition, and epigenetic alterations in RCC subtypes are still poorly understood [ 12 ]. Therefore, understanding the roles of epigenetic modifications and underlying mechanisms in RCC could improve its diagnosis and clinical management.…”

Section: Introductionmentioning

confidence: 99%

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CBX Family Members in Two Major Subtypes of Renal Cell Carcinoma: A Comparative Bioinformatic Analysis

Grimaldi¹,

Affinito²,

Salvatore³

et al. 2022

Diagnostics

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The biological function and clinical values of Chromobox (CBX) family proteins in renal cell carcinoma (RCC) are still poorly investigated. This study aimed to compare the expression profiles and clinical relevance of CBXs between the two most frequent subtypes of RCC, clear cell renal cell carcinomas (ccRCC) and papillary renal cell carcinomas (pRCC), and to investigate whether CBXs would play a more or less similar role in the pathogenesis and progression of these RCC subtypes. Considering these two RCC populations in the TCGA database, we built a bioinformatics framework by integrating a computational pipeline with several online tools. CBXs showed a similar trend in ccRCC and pRCC tissues but with some features specific for each subtype. Specifically, the relative expressions of CBX3 and CBX2 were, respectively, the highest and lowest among all CBXs in both RCC subtypes. These data also found confirmation in cellular validation. Except for CBX4 and CBX8, all others were deregulated in the ccRCC subtype. CBX1, CBX6, and CBX7 were also significantly associated with the tumor stage. Further, low expression levels of CBX1, CBX5, CBX6, CBX7, and high expression of CBX8 were associated with poor prognosis. Otherwise, in the pRCC subtype, CBX2, CBX3, CBX7, and CBX8 were deregulated, and CBX2, CBX6, and CBX7 were associated with the tumor stage. In addition, in pRCC patients, low expression levels of CBX2, CBX4, and CBX7 were associated with an unfavorable prognosis. Similarly, CBX3, CBX6, and CBX7 presented the highest alteration rate in both subtypes and were found to be functionally related to histone binding, nuclear chromosomes, and heterochromatin. Furthermore, CBX gene expression levels correlated with immune cell infiltration, suggesting that CBXs might reflect the immune status of RCC subtypes. Our results highlight similarities and differences of CBXs within the two major RCC subtypes, providing new insights for future eligible biomarkers or possible molecular therapeutic targets for these diseases.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CBX Family Members in Two Major Subtypes of Renal Cell Carcinoma: A Comparative Bioinformatic Analysis

Grimaldi¹,

Affinito²,

Salvatore³

et al. 2022

Diagnostics

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“…The low specificity of PSA may lead to overdiagnosis and treatment of some nonneoplastic lesions of the prostate [ 72 ]. Diagnosis of renal cell cancer is challenging because renal cell cancer is often clinically silent [ 73 ]. The clinical manifestations of early renal cell cancer are variable and nonspecific, and when the renal cancer triad (hematuria, pain, mass) appears, renal cell cancer is usually in an advanced state [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

A Large Genetic Causal Analysis of the Gut Microbiota and Urological Cancers: A Bidirectional Mendelian Randomization Study

Yin,

Liu,

Feng

et al. 2023

Nutrients

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Background: Several observational studies and clinical trials have shown that the gut microbiota is associated with urological cancers. However, the causal relationship between gut microbiota and urological cancers remains to be elucidated due to many confounding factors. Methods: In this study, we used two thresholds to identify gut microbiota GWAS from the MiBioGen consortium and obtained data for five urological cancers from the UK biobank and Finngen consortium, respectively. We then performed a two-sample Mendelian randomization (MR) analysis with Wald ratio or inverse variance weighted as the main method. We also performed comprehensive sensitivity analyses to verify the robustness of the results. In addition, we performed a reverse MR analysis to examine the direction of causality. Results: Our study found that family Rikenellaceae, genus Allisonella, genus Lachnospiraceae UCG001, genus Oscillibacter, genus Eubacterium coprostanoligenes group, genus Eubacterium ruminantium group, genus Ruminococcaceae UCG013, and genus Senegalimassilia were related to bladder cancer; genus Ruminococcus torques group, genus Oscillibacter, genus Barnesiella, genus Butyricicoccus, and genus Ruminococcaceae UCG005 were related to prostate cancer; class Alphaproteobacteria, class Bacilli, family Family XI, genus Coprococcus2, genus Intestinimonas, genus Lachnoclostridium, genus Lactococcus, genus Ruminococcus torques group, and genus Eubacterium brachy group were related to renal cell cancer; family Clostridiaceae 1, family Christensenellaceae, genus Eubacterium coprostanoligenes group, genus Clostridium sensu stricto 1, and genus Eubacterium eligens group were related to renal pelvis cancer; family Peptostreptococcaceae, genus Romboutsia, and genus Subdoligranulum were related to testicular cancer. Comprehensive sensitivity analyses proved that our results were reliable. Conclusions: Our study confirms the role of specific gut microbial taxa on urological cancers, explores the mechanism of gut microbiota on urological cancers from a macroscopic level, provides potential targets for the screening and treatment of urological cancers, and is dedicated to providing new ideas for clinical research.

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“…Renal cell carcinoma (RCC) is the most common and deadliest type of kidney cancer with a mortality rate of 30–40% [ 1 ]. Its incidence has increased rapidly in recent decades [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…Its incidence has increased rapidly in recent decades [ 2 ]. The risk factors include genetic as well as epigenetic alterations [ 3 , 4 ], sex (males more than females), environmental conditions, and lifestyle factors [ 5 ] such as obesity, hypertension, smoking, or long-term dialysis due to chronic kidney disease [ 1 , 6 , 7 ]. Although surgical resection, such as nephrectomy, is the main treatment strategy, adjuvant and targeted therapies are also used in patients with metastatic RCC.…”

Section: Introductionmentioning

confidence: 99%

Compound C Inhibits Renca Renal Epithelial Carcinoma Growth in Syngeneic Mouse Models by Blocking Cell Cycle Progression, Adhesion and Invasion

Lee

Ham

Hwang

et al. 2022

IJMS

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Compound C (CompC), an inhibitor of AMP-activated protein kinase, reduces the viability of various renal carcinoma cells. The molecular mechanism underlying anti-proliferative effect was investigated by flow cytometry and western blot analysis in Renca cells. Its effect on the growth of Renca xenografts was also examined in a syngeneic BALB/c mouse model. Subsequent results demonstrated that CompC reduced platelet-derived growth factor receptor signaling pathways and increased ERK1/2 activation as well as reactive oxygen species (ROS) production. CompC also increased the level of active Wee1 tyrosine kinase (P-Ser642-Wee1) and the inactive form of Cdk1 (P-Tyr15-Cdk1) while reducing the level of active histone H3 (P-Ser10-H3). ROS-dependent ERK1/2 activation and sequential alterations in Wee1, Cdk1, and histone H3 might be responsible for the CompC-induced G2/M cell cycle arrest and cell viability reduction. In addition, CompC reduced the adhesion, migration, and invasion of Renca cells in the in vitro cell systems, and growth of Renca xenografts in the BALB/c mouse model. Taken together, the inhibition of in vivo tumor growth by CompC may be attributed to the blockage of cell cycle progression, adhesion, migration, and invasion of tumor cells. These findings suggest the therapeutic potential of CompC against tumor development and progression.

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Use of Circular RNAs in Diagnosis, Prognosis and Therapeutics of Renal Cell Carcinoma

Cited by 5 publications

References 136 publications

CBX Family Members in Two Major Subtypes of Renal Cell Carcinoma: A Comparative Bioinformatic Analysis

CBX Family Members in Two Major Subtypes of Renal Cell Carcinoma: A Comparative Bioinformatic Analysis

A Large Genetic Causal Analysis of the Gut Microbiota and Urological Cancers: A Bidirectional Mendelian Randomization Study

Compound C Inhibits Renca Renal Epithelial Carcinoma Growth in Syngeneic Mouse Models by Blocking Cell Cycle Progression, Adhesion and Invasion

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