Cancer Genomics & Proteomics最新文献

{"title":"Transcriptomic Profiling Identifies Higher DOT1L Expression as a Candidate Biomarker for a Positive Response to Gemcitabine in Cholangiocarcinoma.","authors":"Jeng-Shiun DU, Sin-Hua Moi, Yu-Hsuan Hung, Ya-Hui Chang, Shu-Jyuan Chang, Min-Hong Wang, Hui-Ching Wang, Chi-Wen Luo, Yu-Ci Yang, Li-Tzong Chen, Mei-Ren Pan","doi":"10.21873/cgp.20598","DOIUrl":"10.21873/cgp.20598","url":null,"abstract":"<p><strong>Background/aim: </strong>Cholangiocarcinoma (CCA) has a poor prognosis, partly due to late diagnosis and limited efficacy of systemic therapies. Gemcitabine remains a commonly used chemotherapeutic agent for CCA; however, the clinical response is heterogeneous, and predictive biomarkers are lacking. Although epigenetic regulators have been implicated in gemcitabine sensitivity in other malignancies, their relevance in CCA has not been explored systematically. This study aimed to identify epigenetic candidates associated with the gemcitabine response in CCA and to validate their functional role.</p><p><strong>Materials and methods: </strong>RNA sequencing was performed on 24 paired non-tumor and tumor bile duct tissues. Differential expression and enrichment analyses were conducted to identify pathways and epigenetic regulators associated with the gemcitabine response. DOT1L was prioritized and experimentally validated in a human CCA cell line (SSP25) using assays for cell proliferation, sphere formation, cell cycle distribution, and EdU incorporation. Mechanistic readouts included cyclin-dependent kinase 2 (CDK2) phosphorylation and caspase-3 cleavage. DOT1L protein expression was examined in patient specimens via immunohistochemistry.</p><p><strong>Results: </strong>Transcriptomic profiling identified DOT1L as the only epigenetic regulator consistently enriched in tumors from gemcitabine responders. The gene ontology (GO) analysis revealed reduced chromatin-remodeling programs in non-responders, consistent with higher DOT1L expression in responders. In SSP25 cells, DOT1L overexpression increased gemcitabine sensitivity, accompanied by S-phase arrest and enhanced apoptosis, as evidenced by increased CDK2 phosphorylation and caspase-3 cleavage. Immunohistochemistry showed higher DOT1L expression in clinical specimens from gemcitabine responders than in those from non-responders.</p><p><strong>Conclusion: </strong>Our integrated transcriptomic and functional analyses support DOT1L as a clinically relevant epigenetic factor associated with the response of CCA to gemcitabine and suggest a mechanistic link involving S-phase regulation and apoptosis. DOT1L may serve as a candidate biomarker and a potential target to improve gemcitabine efficacy in CCA.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 4","pages":"714-729"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulated Circular RNAs in Gastric Cancer: Target Identification and Tools for Therapeutic Intervention.","authors":"Samuele Graziano, Barbara Höllbacher, Ulrich H Weidle","doi":"10.21873/cgp.20590","DOIUrl":"10.21873/cgp.20590","url":null,"abstract":"<p><p>Surveying the literature (PubMed), we have identified upregulated circular RNAs involved in pathogenesis and dissemination of gastric cancer. We have focused on circRNAs that upregulate the following target classes or physiological processes: transmembrane receptors, secreted proteins, RNA metabolism and processing, ubiquitination, WNT signalling, ferroptosis and druggable enzymes. Circular RNAs upregulating targets for approved drugs in GC, such as vascular endothelial growth factor A (VEGF-A) and programmed death-ligand 1 (PD-L1), were identified, validating circRNAs as tools for target identification. We highlight targets and target classes that are frequently affected by circRNAs such as solute carrier (SLC) proteins, subtypes of heterogeneous nuclear RNA (hnRNA), ubiquitin-specific proteases (USPs) and targets related to inhibition of ferroptosis. We also highlight druggable enzymes as targets. We discuss technical issues for inhibition of the identified targets and their corresponding circular RNAs.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 4","pages":"558-587"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beta-site Amyloid Precursor Protein Cleaving Enzyme 1 Overexpression Abrogates ST6GAL1 Mediated Rectal Cancer Chemoradiation Resistance.","authors":"Teresa Chiyanne Beamon, Eman D Mohammed, Jeremie M P Lever, Regina K Irwin, Vivek Somasundaram, Fengyuan Huang, M Chandler McLeod, Karin M Hardiman","doi":"10.21873/cgp.20594","DOIUrl":"10.21873/cgp.20594","url":null,"abstract":"<p><strong>Background/aim: </strong>Sialyltransferase ST6GAL1 is known to be upregulated in various cancer types, including rectal cancer, and is linked to poor prognosis. This enzyme catalyzes the addition of sialic acids to various proteins, altering their activity and function. Our lab has previously shown that ST6GAL1 causes resistance to chemoradiation therapy (CRT) in rectal cancer, via sialylation of tumor necrosis factor receptor 1 (TNFR1). This leads to decreased TNFR1 mediated cell death/apoptosis. We aimed to elucidate whether beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), which cleaves ST6GAL1, has a role in treatment response to CRT and whether its overexpression (OE) could improve response to CRT.</p><p><strong>Materials and methods: </strong>We first assessed BACE1 and ST6GAL1 in pre-treatment biopsies from rectal cancer patients. We then evaluated the effects of BACE1 modulation in CRC cell lines. The high BACE1-expressing CRC cell line SW1463 was utilized for inhibition studies, and SW620 CRC cells lines were additionally lentivirally transfected for OE of BACE1 (validated by flow cytometry, qPCR, Western Blotting, and activity assay). BACE1 OE cells were also utilized for response to CRT.</p><p><strong>Results: </strong>Analysis of patient biopsies showed that BACE1 mRNA was significantly increased in patients with a complete response to CRT. SW1463 colorectal cancer cells treated with a BACE1 inhibitor had increased cell-surface sialylation and increased survival after CRT compared to vehicle-treated cells. BACE1 overexpressing SW620 CRC clones exhibited protein expression and activity of BACE1, with reduced ST6GAL1 protein. BACE1 OE colorectal cancer cells also had significantly increased apoptosis and decreased survival after CRT. BACE1 OE clones had decreased sialylation of the apoptosis receptor, TNFR1.</p><p><strong>Conclusion: </strong>Collectively, we found that overexpressing BACE1 altered ST6GAL1-mediated CRT resistance in CRC cells. BACE1 enzymatic cleavage of ST6GAL1 may be a potential target for improving therapeutic response to CRT in rectal cancer.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 4","pages":"649-663"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reprogramming-driven Proteomic Shifts Mirror Bladder Cancer Progression and Reveal Biomarker Candidates Across Disease Grades.","authors":"Banu Iskender, Mehmet Sarihan, Bengi Su Rumeysa Barlak, Gurler Akpinar, Murat Kasap","doi":"10.21873/cgp.20601","DOIUrl":"10.21873/cgp.20601","url":null,"abstract":"<p><strong>Background/aim: </strong>The acquisition of stem-like properties and increased cellular plasticity is thought to drive tumor progression and therapeutic resistance, but grade-specific molecular trajectories across the epigenetic landscape in bladder cancer remain poorly defined. This study examined the dynamic rewiring of signaling networks and proteomic landscapes during reprogramming of low-grade (HTB-2) and high-grade (HTB-5) bladder cancer cells, and during their subsequent differentiation into embryoid bodies.</p><p><strong>Materials and methods: </strong>Six experimental models were analyzed, including the parental HTB-2 and HTB-5 cells, their Sendai virus-reprogrammed counterparts (rep HTB-2 and rep HTB-5) and embryoid bodies generated from reprogrammed derivatives (rep HTB-2 EB and rep HTB-5 EB), with SV-HUC-1 uroepithelial cells used as a control. Phosphoproteomic and integrated proteomic analyses were performed to define grade-specific signaling architectures and shared plasticity-associated signatures, followed by clinical validation using pan-cancer datasets.</p><p><strong>Results: </strong>Phosphoproteomic reconstruction revealed grade-dependent kinase network architectures associated with stem-like induction. These findings indicate that reprogramming induced cell-line-specific signaling rewiring, with HTB-2 cells showing enhanced MAPK/Src-family-associated phosphorylation and HTB-5 cells showing increased AKT/PRAS40 and STAT1/STAT3 phosphorylation together with reduced ERK1/2-MSK1/2 signaling. During differentiation, low-grade cells underwent metabolic reprogramming, while high-grade cells favored cytoskeletal remodeling and extracellular matrix organization. Integrated proteomics defined a shared plasticity signature, with reprogrammed models recapitulated key bladder cancer features and clinically relevant outcomes.</p><p><strong>Conclusion: </strong>These findings support a hierarchical model of bladder cancer progression where reprogramming induces a transient intermediate state that enables invasive features upon re-differentiation. The study reveals grade-specific signaling and proteomic adaptations, identifying differentiation as a critical window for uncovering prognostic biomarkers and therapeutic targets. Together, these results suggest that reprogrammed bladder cancer models provide a biologically relevant platform to study tumor plasticity, progression and therapeutic vulnerability.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 4","pages":"777-805"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>GGT6</i> as a Prognostic Biomarker and Therapeutic Target in Melanoma Using an Information-theoretical Method.","authors":"Yi-Fei Yang, Yun Geng, Hui Xu, Kazunori Akimoto, Yun-Wen Zheng, Yuyun Xiong, Yu-Mei Li","doi":"10.21873/cgp.20603","DOIUrl":"10.21873/cgp.20603","url":null,"abstract":"<p><strong>Background/aim: </strong>Melanoma is an aggressive malignancy with rising global incidence. While early surgical intervention improves survival in localized cases, treatment resistance and recurrence remain a challenge. This underscores the critical need to identify prognostic biomarkers for early diagnosis, personalized treatment, and novel therapeutic development.</p><p><strong>Materials and methods: </strong>The GSE126076 and melanoma dataset (Skin Cutaneous Melanoma, TCGA, PanCancer Atlas) were analyzed using an information-theoretical method to identify prognostic factors. Survival analysis was performed via Kaplan-Meier curves and log-rank tests to compare high- and low-mRNA expression groups. <i>In vitro</i>, A375 cells and A2058 cells were treated with the GGT inhibitor 6-diazo-5-oxo-L-norleucin (DON). Cell viability was assessed using the CCK-8 assay and intracellular GSH levels were measured following treatment.</p><p><strong>Results: </strong>Through information-theoretic analysis and survival analysis, we identified <i>GGT6</i> as a prognostic gene in melanoma. Survival analysis revealed that high <i>GGT6</i> expression was significantly associated with shorter disease-specific survival across all disease stages. <i>In vitro</i>, 10 μM DON for 72 h reduced A375 cell proliferation by 90.72% versus control (<i>p</i><0.0001), with an IC₅₀ of 5.14 μM; and reduced A2058 cell proliferation by 60.93% (<i>p</i><0.0001), with an IC₅₀ of 7.93 μM. Measurement of GSH levels of A375 and A2058 cells revealed that melanoma cells treated with 10 μM DON exhibited lower GSH levels compared with the respective control groups (<i>p</i><0.0001 and <i>p</i>=0.0042, respectively).</p><p><strong>Conclusion: </strong>Our study is the first to demonstrate the association between <i>GGT6</i> expression levels and melanoma prognosis, and reveals that GGT inhibition suppresses melanoma cell viability. These findings provide new insights into the mechanisms of melanoma development and progression, and suggest GGT as a potential therapeutic target for clinical treatment.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 4","pages":"824-840"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline Variation in Notch Pathway and Survival After Androgen Deprivation Therapy in Prostate Cancer: Implicating <i>YAP1</i> rs1894116 and Focal Adhesion Signaling.","authors":"Wen-Hua Chung, Chi-Fen Chang, Chao-Yuan Huang, Chia-Cheng Yu, Victor C Lin, Te-Ling Lu, Shu-Pin Huang, Bo-Ying Bao","doi":"10.21873/cgp.20604","DOIUrl":"10.21873/cgp.20604","url":null,"abstract":"<p><strong>Background/aim: </strong>Notch signaling exerts context-dependent effects in cancer; however, the prognostic relevance of inherited variation in Notch-related genes in prostate cancer remains unclear. We investigated whether germline single-nucleotide polymorphisms (SNPs) in Notch pathway genes are associated with clinical outcomes in men receiving androgen deprivation therapy (ADT).</p><p><strong>Patients and methods: </strong>We genotyped 222 SNPs across 24 Notch pathway-related genes in 630 patients with advanced prostate cancer. Associations with cancer-specific survival (CSS) and overall survival (OS) were assessed using Cox proportional hazards models. Integrative bioinformatics analyses, including pooled transcriptomic dataset analysis, expression quantitative trait locus analysis, and pathway enrichment, were performed to assess functional relevance.</p><p><strong>Results: </strong>Multiple SNPs were significantly associated with CSS and OS, with Yes1-associated transcriptional regulator (<i>YAP1</i>) rs1894116 showing the strongest prognostic signal. The minor G allele was associated with a 26% reduction in prostate cancer-specific mortality and a 22% reduction in all-cause mortality, independent of established clinical predictors. Functional annotation suggested that rs1894116 may be linked to increased <i>YAP1</i> expression. Pooled transcriptomic analyses showed lower <i>YAP1</i> expression in tumors than in normal tissue, while higher <i>YAP1</i> expression correlated with more favorable outcomes. <i>YAP1</i>-correlated genes were enriched in the focal adhesion pathway, suggesting a tumor-suppressive <i>YAP1</i>-focal adhesion axis, particularly involving vinculin.</p><p><strong>Conclusion: </strong>Germline variation in the Notch-YAP axis, notably <i>YAP1</i> rs1894116, predicts survival in patients with prostate cancer treated with ADT. Elevated <i>YAP1</i> expression and coordinated activation of focal adhesion components may be associated with less aggressive disease. These findings provide mechanistic insight into Notch signaling in prostate cancer and highlight <i>YAP1</i> and its variants as potential biomarkers for risk stratification and personalized therapy.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 4","pages":"841-855"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulated CircRNAs With Efficacy in Preclinical <i>In Vivo</i> Models Reveal New Targets for Therapeutic Intervention in Glioma.","authors":"Satu Nahkuri, Ulrich H Weidle","doi":"10.21873/cgp.20591","DOIUrl":"10.21873/cgp.20591","url":null,"abstract":"<p><p>There is a significant need to improve treatment efficacy for patients with glioma. Therefore, we have analyzed the literature for the role of circular RNAs (circRNAs) with respect to selected pathology-related topics of glioma. We have focused on upregulated circRNAs with efficacy in preclinical <i>in vivo</i> models. The identified circRNAs cover the following topics: Temozolomide (TMZ) resistance, transmembrane and secreted proteins, wingless-related integration site (WNT) signaling, cytoskeleton dynamics, cell-cell and cell-extracellular matrix interactions, as well as circRNAs with additional functions. We describe possible therapeutic tools and challenges with respect to delivery of the corresponding inhibitory agents.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 4","pages":"588-616"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LGALS3BP Links Centrosomes and Mitochondria to Maintain Energetic Fitness and Restrain Compensatory Lipid Catabolic Reprogramming in Hepatocellular Carcinoma.","authors":"Jun Eul Hwang, Hyun Jeong Shim, Hyun Jin Bang, Hyeon-Jong Kim, Sung Yun Jung, Ik-Joo Chung, Sang-Hee Cho, Dae-Hwan Kim","doi":"10.21873/cgp.20581","DOIUrl":"10.21873/cgp.20581","url":null,"abstract":"<p><strong>Background/aim: </strong>Hepatocellular carcinoma (HCC) exhibits substantial metabolic plasticity that supports tumor progression and therapeutic resistance. LGALS3BP has been primarily characterized as a secreted immunomodulatory protein; however, its cell-intrinsic role in regulating subcellular organization and metabolism in HCC remains poorly understood.</p><p><strong>Materials and methods: </strong>Transcriptomic analyses of public HCC cohorts were performed to assess metabolic programs associated with LGALS3BP expression. Proteomic profiling was conducted to define the LGALS3BP interactome. Mitochondrial function was evaluated by measuring adenosine triphosphate (ATP) levels, mitochondrial membrane potential (ΔΨm), and AMP-activated protein kinase (AMPK) activation. Lipid metabolic programs were assessed by gene expression analyses and lipid accumulation assays. Clinical relevance was independently validated in an institutional HCC cohort.</p><p><strong>Results: </strong>Low LGALS3BP expression was associated with activation of peroxisome proliferator-activated receptor alpha (PPARα)-driven peroxisomal and lipid catabolic gene programs. Proteomic analyses revealed that LGALS3BP associates with centrosomal γ-tubulin ring complex components and mitochondrial proteins, suggesting a role in centrosome-mitochondria subcellular organization. Functionally, LGALS3BP deficiency resulted in impaired mitochondrial energetic fitness, reduced ATP production, and activation of AMPK. This energetic stress was accompanied by induction of PPARα and compensatory lipid catabolic transcriptional programs. Consistent inverse associations between LGALS3BP expression and PPARα-peroxisome-related genes, including PPARA, ACOX1, EPHX2, and SCP2, were observed across public HCC datasets and were independently validated in an institutional HCC patient cohort.</p><p><strong>Conclusion: </strong>LGALS3BP acts as a cell-intrinsic organizer that links centrosomal architecture to mitochondrial energetic homeostasis in HCC. Loss of this organizational axis induces mitochondrial energetic stress and promotes compensatory PPARα-peroxisome-mediated lipid catabolic reprogramming, highlighting a previously unrecognized connection between subcellular organization and metabolic plasticity in liver cancer.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 3","pages":"393-406"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Profiling Reveals HECTD4-dependent Regulation of Protein Ubiquitination and Signaling Pathways in Prostate Cancer.","authors":"Yasuo Takashima, Masami Tanaka, Kengo Yoshii, Tomohito Yagi, Aya Miyagawa-Hayashino, Kei Tashiro","doi":"10.21873/cgp.20583","DOIUrl":"10.21873/cgp.20583","url":null,"abstract":"<p><strong>Background/aim: </strong>Prostate cancer (PCa) is a leading malignancy in men, and understanding its molecular mechanisms is crucial for advancing therapeutic strategies. Ubiquitination, a key post-translational modification, regulates protein degradation and signaling, playing a vital role in cancer progression. This study focuses on HECTD4, a HECT-type E3 ubiquitin ligase, to identify its ubiquitination targets and understand its role in PCa.</p><p><strong>Materials and methods: </strong>HECTD4 knockdown was performed in LNCaP, PC-3, and DU145 PCa cell lines. A combination of semi-quantitative PCR and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify proteins with altered expression and ubiquitination profiles. Gene ontology analysis, pathway analysis, and a proliferation assay were conducted to explore the biological significance of HECTD4.</p><p><strong>Results: </strong>We identified 1,605 downregulated and 1,736 upregulated proteins upon HECTD4 knockdown. Key proteins involved in tumor suppression and cell cycle regulation, such as NUSAP1, CDK6, and MED13L, were ubiquitinated by HECTD4. Functional annotations revealed that these targets are associated with critical pathways, including phosphoinositide 3-kinase (PI3K)-AKT, Ras-mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR), as well as immune infiltration, drug response, and survival analysis.</p><p><strong>Conclusion: </strong>HECTD4 regulates protein stability and activation through ubiquitination, impacting cell cycle progression, tumor suppression, and immune response in PCa. These findings suggest that HECTD4 is a promising therapeutic target, with potential applications in drug development aimed at disrupting oncogenic signaling and enhancing treatment efficacy.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 3","pages":"430-447"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Multi-omics PTM Atlas Reveals Key Insights into Metabolic Reprogramming in Colorectal Cancer.","authors":"Tianyuan Li, Jingjing Dong, Yujie Zhang, Erjiao Hao, Jie DU, Min Feng, Feng Zhu, Juan Qin, Wei Zhang, Yong Dai","doi":"10.21873/cgp.20584","DOIUrl":"10.21873/cgp.20584","url":null,"abstract":"<p><strong>Background/aim: </strong>Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with limited effective targeted therapies. Metabolic reprogramming is a hallmark of cancer, and post-translational modifications (PTMs), such as phosphorylation, ubiquitination, and malonylation, play critical roles in regulating metabolic pathways. However, their contribution to metabolic reprogramming in CRC remains unclear.</p><p><strong>Materials and methods: </strong>Phosphorylation, ubiquitination, and malonylation were analyzed in paired CRC and adjacent normal tissues using high-resolution mass spectrometry. Differential PTM patterns were analyzed, followed by identification of key regulatory enzymes and modification sites. Functional enrichment, protein-protein interaction (PPI) networks, and multi-omics integration were used to explore PTMs' role in CRC metabolism.</p><p><strong>Results: </strong>We identified 59 differential phosphorylation sites, 263 ubiquitination sites, and 64 malonylation sites in CRC tissues compared with normal tissues, affecting key metabolic enzymes such as IDH1, LDHA, PDHA1, and GAPDH. Altered ubiquitination of IDH1 and LDHA may be associated with changes in protein stability and activity. Phosphorylation of PDHA1 correlated with its modified levels, potentially promoting glycolytic preference in CRC, while increased malonylation of GAPDH may influence its enzymatic activity and glycolytic flux. Protein interaction and pathway analyses further revealed a PTM-regulated metabolic network, suggesting a potential role of PTMs in CRC metabolic reprogramming.</p><p><strong>Conclusion: </strong>This study suggests that PTMs may contribute to metabolic reprogramming in CRC by modulating key metabolic enzymes, including IDH1, LDHA, PDHA1, and GAPDH. These modifications may influence glycolysis and energy metabolism, highlighting PTM-regulated pathways as potential therapeutic targets. The integrated PTM atlas offers insights into the metabolic landscape of CRC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 3","pages":"448-469"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}