
DOI . ORG {
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Title[redir]:
Loss of AR-regulated AFF3 contributes to prostate cancer progression and reduces ferroptosis sensitivity by downregulating ACSL4 based on single-cell sequencing analysis | Apoptosis
Description:
Prostate cancer (PCa) is one of the most common cancers affecting the health of men worldwide. Castration-resistant prostate cancer (CRPC), the advanced and refractory phase of prostate cancer, has multiple mechanisms of resistance to androgen deprivation therapy (ADT) such as AR mutations, aberrant androgen synthase, and abnormal expression of AR-related genes. Based on the research of the AR pathway, new drugs for the treatment of CRPC have been developed in clinical practice, such as Abiraterone and enzalutamide. However, many areas in this pathway are still worth exploring. In this study, single-cell sequencing analysis was utilized to scrutinize significant genes in the androgen receptor (AR) pathway related to CRPC. Our analysis of single-cell sequencing combined with bulk-cell sequencing revealed a substantial downregulation of AR-regulated AFF3 in CRPC. Overexpression of AFF3 restricted the proliferation and migration of prostate cancer cells whilst also increasing their sensitivity towards enzalutamide, while knockdown of AFF3 had the opposite effect. To elucidate the mechanism of tumor inhibition by AFF3, we applied GSVA and GSEA to investigate the metabolic pathways related to AFF3 and revealed that AFF3 had an impact on fatty acids metabolism and ferroptosis through the regulation of ACSL4 protein expression. Based on correlation analysis and flow cytometry, we can speculate that AFF3 can impact the sensitivity of the CRPC cell lines to the ferroptosis inducer (RSL3) by regulating ACSL4. Therefore, our findings may provide new insights into the mechanisms of drug resistance in CRPC, and AFF3 may serve as a novel prognostic biomarker in prostate cancer.
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Keywords {🔍}
pubmed, article, cancer, google, scholar, prostate, cas, central, androgen, ferroptosis, aff, analysis, cell, chen, receptor, zhang, castrationresistant, sequencing, res, singlecell, wei, nat, data, crpc, mechanisms, access, gene, material, supplementary, research, acsl, fan, resistance, rev, oncol, privacy, cookies, content, information, progression, based, expression, genes, enzalutamide, study, cells, tumor, open, clin, eur,
Topics {✒️}
androgen metabolite 5alpha-androstane-3beta month download article/chapter single-cell sequencing combined single-cell sequencing analysis androgen-repressed survival factor ferroptosis-related gene signature castration-resistant prostate cancer castration–resistant prostate cancer bulk-cell sequencing revealed clinical multi-kinase inhibitors ar-regulated zic5 contributes chemoproteomics-based kinome profiling single-cell sequencing article apoptosis aims full article pdf ar-regulated aff3 contributes single-cell transcriptomics androgen-induced translation related subjects privacy choices/manage cookies androgen deprivation therapy ar-related genes lncap prostate xenografts aromatase inhibitor resistance prostate cancer cells prostate cancer risk article fan aberrant androgen synthase androgen levels increase renal cell carcinoma crpc cell lines common cancers affecting scrutinize significant genes van veldhoven pp recurrent prostate cancer acsl4 protein expression open platform zhongliang ma steroidogenesis inhibitors alter regulates pufa oxidation prostate cancer based androgen receptor check access instant access holds exclusive rights decode tumor microenvironment metabolic pathways related rna-seq data lymphoid nuclear protein androgens markedly stimulate
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headline:Loss of AR-regulated AFF3 contributes to prostate cancer progression and reduces ferroptosis sensitivity by downregulating ACSL4 based on single-cell sequencing analysis
description:Prostate cancer (PCa) is one of the most common cancers affecting the health of men worldwide. Castration-resistant prostate cancer (CRPC), the advanced and refractory phase of prostate cancer, has multiple mechanisms of resistance to androgen deprivation therapy (ADT) such as AR mutations, aberrant androgen synthase, and abnormal expression of AR-related genes. Based on the research of the AR pathway, new drugs for the treatment of CRPC have been developed in clinical practice, such as Abiraterone and enzalutamide. However, many areas in this pathway are still worth exploring. In this study, single-cell sequencing analysis was utilized to scrutinize significant genes in the androgen receptor (AR) pathway related to CRPC. Our analysis of single-cell sequencing combined with bulk-cell sequencing revealed a substantial downregulation of AR-regulated AFF3 in CRPC. Overexpression of AFF3 restricted the proliferation and migration of prostate cancer cells whilst also increasing their sensitivity towards enzalutamide, while knockdown of AFF3 had the opposite effect. To elucidate the mechanism of tumor inhibition by AFF3, we applied GSVA and GSEA to investigate the metabolic pathways related to AFF3 and revealed that AFF3 had an impact on fatty acids metabolism and ferroptosis through the regulation of ACSL4 protein expression. Based on correlation analysis and flow cytometry, we can speculate that AFF3 can impact the sensitivity of the CRPC cell lines to the ferroptosis inducer (RSL3) by regulating ACSL4. Therefore, our findings may provide new insights into the mechanisms of drug resistance in CRPC, and AFF3 may serve as a novel prognostic biomarker in prostate cancer.
datePublished:2024-03-13T00:00:00Z
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Single-cell sequencing
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description:Prostate cancer (PCa) is one of the most common cancers affecting the health of men worldwide. Castration-resistant prostate cancer (CRPC), the advanced and refractory phase of prostate cancer, has multiple mechanisms of resistance to androgen deprivation therapy (ADT) such as AR mutations, aberrant androgen synthase, and abnormal expression of AR-related genes. Based on the research of the AR pathway, new drugs for the treatment of CRPC have been developed in clinical practice, such as Abiraterone and enzalutamide. However, many areas in this pathway are still worth exploring. In this study, single-cell sequencing analysis was utilized to scrutinize significant genes in the androgen receptor (AR) pathway related to CRPC. Our analysis of single-cell sequencing combined with bulk-cell sequencing revealed a substantial downregulation of AR-regulated AFF3 in CRPC. Overexpression of AFF3 restricted the proliferation and migration of prostate cancer cells whilst also increasing their sensitivity towards enzalutamide, while knockdown of AFF3 had the opposite effect. To elucidate the mechanism of tumor inhibition by AFF3, we applied GSVA and GSEA to investigate the metabolic pathways related to AFF3 and revealed that AFF3 had an impact on fatty acids metabolism and ferroptosis through the regulation of ACSL4 protein expression. Based on correlation analysis and flow cytometry, we can speculate that AFF3 can impact the sensitivity of the CRPC cell lines to the ferroptosis inducer (RSL3) by regulating ACSL4. Therefore, our findings may provide new insights into the mechanisms of drug resistance in CRPC, and AFF3 may serve as a novel prognostic biomarker in prostate cancer.
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Cancer Research
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