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Renal Cell Carcinoma: Novel Insights into Pathophysiology, Diagnosis and Therapy

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 2545

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Special Issue Editor

Prof. Dr. Giuseppe Lucarelli

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Andrology and Kidney Transplantation Unit, Department of Emergency and Organ Transplantation—Urology, University of Bari “Aldo Moro”, 70124 Bari, Italy
Interests: kidney cancer; prostate cancer; kidney transplantation; metabolomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Renal cell carcinoma (RCC) is among the top 10 malignancies affecting adults globally. In the early stages, the disease is frequently asymptomatic and incidentally diagnosed by imaging, having a good prognosis. Conversely, ccRCC has a high mortality rate in advanced phases due to poor responses to radiotherapy and chemotherapy. Over the last decade, significant progress has been made in identifying molecular alterations driving ccRCC development thanks to the progressive use of high-throughput technologies. In addition, the introduction of robotic surgery and novel targeted therapies have shed new light on the treatment of RCC.

This Special Issue of the International Journal of Molecular Sciences is dedicated to studies exploring the application of different approaches to understand the alterations of biological systems occurring in the pathogenesis of RCC, as well as minimally invasive treatment and translational research for the diagnosis and management of this tumor.

Prof. Dr. Giuseppe Lucarelli
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

renal cell carcinoma
biomarker
diagnosis
robot-assisted surgery
therapy

Published Papers (3 papers)

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Research

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19 pages, 5038 KiB

Open AccessArticle

A1CF Binding to the p65 Interaction Site on NKRF Decreased IFN-β Expression and p65 Phosphorylation (Ser536) in Renal Carcinoma Cells

by Yamin Liu, Jieru Yang, Dunchu Weng and Yajun Xie

Int. J. Mol. Sci. 2024, 25(7), 3576; https://doi.org/10.3390/ijms25073576 - 22 Mar 2024

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Abstract

Apobec-1 complementation factor (A1CF) functions as an RNA-binding cofactor for APO-BEC1-mediated C-to-U conversion during RNA editing and as a hepatocyte-specific regulator in the alternative pre-mRNA splicing of metabolic enzymes. Its role in RNA editing has not been clearly established. Western blot, co-immunoprecipitation (Co-IP), immunofluorescence (IF), methyl thiazolyl tetrazolium (MTT), and 5-ethynyl-2′-deoxyuridine (EdU) assays were used to examine the role of A1CF beyond RNA editing in renal carcinoma cells. We demonstrated that A1CF interacts with NKRF, independent of RNA and DNA, without affecting its expression or nuclear translocation; however, it modulates p65(Ser536) phosphorylation and IFN-β levels. Truncation of A1CF or deletion on NKRF revealed that the RRM1 domain of A1CF and the p65 binding motif of NKRF are required for their interaction. Deletion of RRM1 on A1CF abrogates NKRF binding, and the decrease in IFN-β expression and p65(Ser536) phosphorylation was induced by A1CF. Moreover, full-length A1CF, but not an RRM1 deletion mutant, promoted cell proliferation in renal carcinoma cells. Perturbation of A1CF levels in renal carcinoma cells altered anchorage-independent growth and tumor progression in nude mice. Moreover, p65(Ser536) phosphorylation and IFN-β expression were lower, but ki67 was higher in A1CF-overexpressing tumor tissues of a xenograft mouse model. Notably, primary and metastatic samples from renal cancer patients exhibited high A1CF expression, low p65(Ser536) phosphorylation, and decreased IFN-β levels in renal carcinoma tissues compared with the corresponding paracancerous tissues. Our results indicate that A1CF-decreased p65(Ser536) phosphorylation and IFN-β levels may be caused by A1CF competitive binding to the p65-combined site on NKRF and demonstrate the direct binding of A1CF independent of RNA or DNA in signal pathway regulation and tumor promotion in renal carcinoma cells. Full article

(This article belongs to the Special Issue Renal Cell Carcinoma: Novel Insights into Pathophysiology, Diagnosis and Therapy)

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16 pages, 3719 KiB

Open AccessArticle

Therapeutic Efficacy of YM155 to Regulate an Epigenetic Enzyme in Major Subtypes of RCC

by Seong Hwi Hong, Young Ju Lee, Eun Bi Jang, Hyun Ji Hwang, Eun Song Kim, Da Hyeon Son, Sung Yul Park, Hong Sang Moon and Young Eun Yoon

Int. J. Mol. Sci. 2024, 25(1), 216; https://doi.org/10.3390/ijms25010216 - 22 Dec 2023

Viewed by 808

Abstract

Renal cell carcinoma (RCC) is the most common type of kidney cancer and includes more than 10 subtypes. Compared to the intensively investigated clear cell RCC (ccRCC), the underlying mechanisms and treatment options of other subtypes, including papillary RCC (pRCC) and chromogenic RCC (chRCC), are limited. In this study, we analyzed the public databases for ccRCC, pRCC, and chRCC and found that BIRC5 was commonly overexpressed in a large cohort of pRCC and chRCC patients as well as ccRCC and was closely related to the progression of RCCs. We investigated the potential of BIRC5 as a therapeutic target for these three types of RCCs. Loss and gain of function studies showed the critical role of BIRC5 in cancer growth. YM155, a BIRC5 inhibitor, induced a potent tumor-suppressive effect in the three types of RCC cells and xenograft models. To determine the mechanism underlying the anti-tumor effects of YM155, we examined epigenetic modifications in the BIRC5 promoter and found that histone H3 lysine 27 acetylation (H3K27Ac) was highly enriched on the promoter region of BIRC5. Chromatin-immunoprecipitation analysis revealed that H3K27Ac enrichment was significantly decreased by YM155. Immunohistochemistry of xenografted tissue showed that overexpression of BIRC5 plays an important role in malignancy in RCC. Furthermore, high expression of P300 was significantly associated with the progression of RCC. Our findings demonstrate the P300-H3K27Ac-BIRC5 cascade in three types of RCC and provide a therapeutic path for future research on RCC. Full article

(This article belongs to the Special Issue Renal Cell Carcinoma: Novel Insights into Pathophysiology, Diagnosis and Therapy)

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Review

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14 pages, 1247 KiB

Open AccessReview

Unlocking Precision Medicine: Liquid Biopsy Advancements in Renal Cancer Detection and Monitoring

by Felice Crocetto, Alfonso Falcone, Benito Fabio Mirto, Enrico Sicignano, Giovanni Pagano, Fabrizio Dinacci, Domenico Varriale, Fabio Machiella, Gaetano Giampaglia, Armando Calogero, Filippo Varlese, Raffaele Balsamo, Francesco Trama, Antonella Sciarra, Francesco Del Giudice, Gian Maria Busetto, Matteo Ferro, Giuseppe Lucarelli, Francesco Lasorsa, Ciro Imbimbo and Biagio Barone Show full author list Hide full author list

Int. J. Mol. Sci. 2024, 25(7), 3867; https://doi.org/10.3390/ijms25073867 - 30 Mar 2024

Viewed by 642

Abstract

Renal cell carcinoma (RCC) remains a formidable diagnostic challenge, especially in the context of small renal masses. The quest for non-invasive screening tools and biomarkers has steered research towards liquid biopsy, focusing on microRNAs (miRNAs), exosomes, and circulating tumor cells (CTCs). MiRNAs, small non-coding RNAs, exhibit notable dysregulation in RCC, offering promising avenues for diagnosis and prognosis. Studies underscore their potential across various biofluids, including plasma, serum, and urine, for RCC detection and subtype characterization. Encouraging miRNA signatures show correlations with overall survival, indicative of their future relevance in RCC management. Exosomes, with their diverse molecular cargo, including miRNAs, emerge as enticing biomarkers, while CTCs, emanating from primary tumors into the bloodstream, provide valuable insights into cancer progression. Despite these advancements, clinical translation necessitates further validation and standardization, encompassing larger-scale studies and robust evidence generation. Currently lacking approved diagnostic assays for renal cancer, the potential future applications of liquid biopsy in follow-up care, treatment selection, and outcome prediction in RCC patients are profound. This review aims to discuss and highlight recent advancements in liquid biopsy for RCC, exploring their strengths and weaknesses in the comprehensive management of this disease. Full article

(This article belongs to the Special Issue Renal Cell Carcinoma: Novel Insights into Pathophysiology, Diagnosis and Therapy)

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