bims-prolim 2025-06-01 papers

bims-prolim

Biomed News

on Protein lipidation, metabolism and cancer

Issue of 2025–06–01
seventeen papers selected by
Bruna Martins Garcia, CABIMER

The regulatory role of protein lactylation in various diseases: Special focus on the regulatory role of non-histone lactylation.
Lactylation in Tumor Microenvironment and Immunotherapy Resistance: New Mechanisms and Challenges.
Lactate-mediated metabolic reprogramming of tumor-associated macrophages: implications for tumor progression and therapeutic potential.
Lactate trains immunity.
RACGAP1 and MKI67 are potential prognostic biomarker in hepatocellular carcinoma caused by HBV/HCV via lactylation.
Dual Regulation of Sprouty 4 Palmitoylation by ZDHHC7 and Palmitoyl-Protein Thioesterase 1: A Potential Therapeutic Strategy for Cisplatin-Resistant Osteosarcoma.
SMAD2 S-palmitoylation promotes its linker region phosphorylation and TH17 cell differentiation in a mouse model of multiple sclerosis.
Integrative multi-omics reveal NSUN2 facilitates glycolysis and histone lactylation-driven immune evasion in renal carcinoma.
LDHA-mediated YAP lactylation promotes the tumor progression of hepatocellular carcinoma by inducing YAP dephosphorylation and activation.
Post-translational modifications and the reprogramming of tumor metabolism.
Post-Translational Modifications in Multiple Myeloma: Mechanisms of Drug Resistance and Therapeutic Opportunities.
Glycosylated protein-related microenvironmental features in breast cancer are associated with patient prognosis.
GPR55 senses lactate to sustain motility in prostate cancer cells.
Comprehensive analysis of a palmitoylation-related prognostic signature in colorectal cancer: Implications for immune therapy and personalized treatment.
Research trends on lactate in cancer: a bibliometric analysis and comprehensive review (2015-2024).
Exploring succinylation in proteins: A comprehensive review from functional improvements to application potential.
Multifaceted roles of lactate dehydrogenase in liver cancer (Review).

Gene. 2025 May 27. pii: S0378-1119(25)00384-1. [Epub ahead of print] 149595

The regulatory role of protein lactylation in various diseases: Special focus on the regulatory role of non-histone lactylation.

Peipei Wang, Kexin Lin, Degao Huang, Zihan Jiang, Linchuan Liao, Xia Wang.

  Lactylation, an emerging form of post-translational modification derived from lactate, plays a pivotal role in numerous cellular processes such as tumor proliferation, metabolism, inflammation, and embryonic development. However, the precise molecular mechanisms by which lactylation controls these biological functions in both physiological and pathological contexts remain elusive. This review summarizes the latest reported regulatory mechanisms of protein lactylation in various diseases since 2024, introducing the latest research progress regarding the regulatory functions of protein lactylation in pathological processes, with particular attention to the regulatory mechanisms of non-histone lactylation modification in diseases. Finally, it outlines the potential of targeted lactylation therapy, proposes the main directions for future research, and emphasizes its scientific significance for future studies.

Keywords:  Cardiovascular diseases; Inflammatory diseases; Lactylation; Neurological diseases; Non-histone protein; Tumors

DOI:  https://doi.org/10.1016/j.gene.2025.149595
Cancer Lett. 2025 May 28. pii: S0304-3835(25)00402-1. [Epub ahead of print] 217835

Lactylation in Tumor Microenvironment and Immunotherapy Resistance: New Mechanisms and Challenges.

Wenlong Zhu, Chang Fan, Yizhuo Hou, Yanjie Zhang.

  Tumor microenvironment (TME) is a highly intricate and variable system. The Warburg effect has made researchers further realize that TME is a highly hypoxic microenvironment. Currently, it is reported that lactate is not merely a metabolic waste but also serves important biological functions, which provides a large number of reaction substrates for lactylation. Post-translational modification (PTM) is crucial for signaling and physiological regulation in both normal and cancer cells. Various PTMs play pathological roles in tumor proliferation, metabolism, and the remodeling of the tumor immunosuppressive microenvironment (TIME). Lactylation, as a newly reported PTM, plays an important role in shaping TIME and aggravating tumor immunotherapy resistance. Numerous studies have demonstrated that histone lactylation can directly stimulate gene transcription within chromatin, thereby contributing to tumor promotion and diminishing the efficacy of therapeutic agents against tumors. Advancements in multi-omics technology enable researchers to investigate lactylation-related substrates more effectively. By precisely targeting these sites, it is possible to reduce histone lactylation in order to mitigate their effects on tumor immune resistance. Despite the existence of numerous studies, there remains a notable deficiency of systematic reviews in this field. Therefore, this review focuses on the novel mechanisms of lactylation that promote tumor progression and its impact on tumor immune resistance. Finally, we propose relevant therapeutic regimens for reversing lactylation to guide tumor combined therapy, thus providing benefits upon more patients with tumor immune resistance.

Keywords:  Immunotherapy resistance; Lactylation; Tumor microenvironment

DOI:  https://doi.org/10.1016/j.canlet.2025.217835
Front Immunol. 2025 ;16 1573039

Lactate-mediated metabolic reprogramming of tumor-associated macrophages: implications for tumor progression and therapeutic potential.

Xiaohan Jin, Ni Zhang, Tinghao Yan, Jingyang Wei, Lingli Hao, Changgang Sun, Haibo Zhao, Shulong Jiang.

  The tumor microenvironment (TME) is characterized by distinct metabolic adaptations that not only drive tumor progression but also profoundly influence immune responses. Among these adaptations, lactate, a key metabolic byproduct of aerobic glycolysis, accumulates in the TME and plays a pivotal role in regulating cellular metabolism and immune cell function. Tumor-associated macrophages (TAMs), known for their remarkable functional plasticity, serve as critical regulators of the immune microenvironment and tumor progression. Lactate modulates TAM polarization by influencing the M1/M2 phenotypic balance through diverse signaling pathways, while simultaneously driving metabolic reprogramming. Furthermore, lactate-mediated histone and protein lactylation reshapes TAM gene expression, reinforcing their immunosuppressive properties. From a therapeutic perspective, targeting lactate metabolism has shown promise in reprogramming TAMs and enhancing anti-tumor immunity. Combining these metabolic interventions with immunotherapies may further augment treatment efficacy. This review underscores the crucial role of lactate in TAM regulation and tumor progression, highlighting its potential as a promising therapeutic target in cancer treatment.

Keywords:  cancer therapy; immune regulation; lactate metabolism; metabolic reprogramming; tumor microenvironment; tumor-associated macrophages

DOI:  https://doi.org/10.3389/fimmu.2025.1573039
Trends Immunol. 2025 May 26. pii: S1471-4906(25)00123-1. [Epub ahead of print]

Lactate trains immunity.

Alba Llibre, Claudio Mauro.

Understanding the mechanisms implicated in the establishment of trained immunity could aid the design of novel therapeutic approaches. By studying Bacille Calmette-Guerin (BCG) vaccination in a human cohort, Ziogas and colleagues demonstrate the role of lactate generation and its use for histone lactylation as a key mechanism for establishing innate immune memory.

DOI: https://doi.org/10.1016/j.it.2025.05.002
Front Oncol. 2025 ;15 1537084

RACGAP1 and MKI67 are potential prognostic biomarker in hepatocellular carcinoma caused by HBV/HCV via lactylation.

Muhammad Muddasar Saeed, Xinying Ma, Xinyu Fu, Ikram Ullah, Tanveer Ali, Changchuan Bai, Ying Liu, Chengyong Dong, Xiaonan Cui.

   Introduction: Hepatocellular carcinoma (HCC) is recognized as the prime and lethal form of liver cancer caused by the hepatitis B virus (HBV) and hepatitis C virus (HCV) globally. Lactate is an end product of glycolysis that influences epigenetic expression through histone lactylation. While MKI67 and RACGAP1 play crucial roles in HBV- and HCV-related HCC. However, the role of lactylation-related genes (LRGs) effects in this context remains unclear. This study innovatively explored the role of LRGs in HBV/HCV-associated HCC, identifying novel biomarkers for diagnosis and prognosis.
Methods: The present study used various online databases for analysis, and the findings were validated via immunohistochemical (IHC) analysis of HCC patient samples (n=60).
Results: We identified six signature LRGs (ALB, G6PD, HMGA1, MKI67, RACGAP1, and RFC4) possess prognostic potential, correlation with immune infiltration, and lactylation-related pathways, providing novel insights into tumor microenvironment (TME) of HCC. Moreover, MKI67 and RACGAP1 were significantly associated with HBV- and HCV-related HCC. IHC confirmed these findings, with high expression of MKI67 and RACGAP1 was significantly linked with HBV/HCV-associated HCC compared to non-viral HCC. The expression is also significantly associated with key clinical variables.
Conclusion: Our results suggest that MKI67 and RACGAP1 could serve as promising biomarkers for detecting and predicting HCC caused by HBV/HCV via lactylation, opening a new direction for immune-targeted therapies.

Keywords:  HCV-HCC; MKI67; RACGAP1; bioinformatic analysis; immune infiltrations; lactylation

DOI:  https://doi.org/10.3389/fonc.2025.1537084
Research (Wash D C). 2025 ;8 0708

Dual Regulation of Sprouty 4 Palmitoylation by ZDHHC7 and Palmitoyl-Protein Thioesterase 1: A Potential Therapeutic Strategy for Cisplatin-Resistant Osteosarcoma.

Tianlong Huang, Yifan Chen, Qiangqiang Zhao, Xin Wu, Hongxing Li, Xin Luo, Yang Su, Shengqun Zhang, Pan Liu, Ning Tang.

Background: Osteosarcoma (OS) is a primary malignant bone tumor predominantly affecting adolescents. Chemotherapeutic agents, such as cisplatin, are commonly used in OS treatment; however, drug resistance markedly undermines treatment efficacy and contributes to reduced patient survival. The mechanisms underlying cisplatin resistance remain poorly understood. Recently, palmitoyl-protein thioesterase 1 (PPT1), a depalmitoylation enzyme, has attracted attention for its role in tumorigenesis and drug resistance. Investigating the mechanisms of PPT1 may offer new strategies to overcome resistance. Methods: This study analyzed multiple Gene Expression Omnibus datasets and utilized the OncoPredict tool to demonstrate the elevated expression of PPT1 in OS and its critical role in cisplatin resistance. By combining single-cell analysis with in vitro and in vivo experiments, we explored how PPT1 influences OS development through depalmitoylation and assessed the antitumor effects of the PPT1 inhibitor Ezurpimtrostat (GNS561), as well as its synergistic effects when combined with cisplatin. Results: We demonstrated that Sprouty 4 (SPRY4) undergoes a dynamic palmitoylation cycle regulated by zinc finger DHHC-type palmitoyl transferase 7 (ZDHHC7) and PPT1, which modulates mitogen-activated protein kinase (MAPK) signaling and subsequently affects tumor cell proliferation, migration, apoptosis, and drug resistance. Further validation confirmed the effectiveness of the PPT1 inhibitor GNS561 in overcoming cisplatin resistance. Notably, GNS561 exhibited a significant synergistic effect when used in combination with cisplatin, greatly enhancing the sensitivity of cisplatin-resistant cells. Conclusion: This study highlights the pivotal role of PPT1 in OS resistance mechanisms. PPT1 and ZDHHC7 regulate SPRY4 through a dynamic palmitoylation-depalmitoylation cycle that modulates MAPK signaling activation and contributes to OS cell proliferation, migration, and drug resistance. As a PPT1 inhibitor, GNS561 not only inhibits OS cell proliferation but also demonstrates synergistic effects with cisplatin, significantly enhancing cisplatin sensitivity in resistant cells and promoting apoptosis. Our findings offer a novel approach for targeting PPT1 in therapeutic strategies. GNS561 holds promise as an adjunctive therapy when combined with cisplatin, potentially overcoming resistance and improving efficacy, thereby enhancing the prognosis for OS patients. Future studies should further investigate the clinical potential of GNS561 and optimize OS treatment strategies.

DOI: https://doi.org/10.34133/research.0708
Sci Signal. 2025 May 27. 18(888): eadr2008

SMAD2 S-palmitoylation promotes its linker region phosphorylation and TH17 cell differentiation in a mouse model of multiple sclerosis.

Mingming Zhang, Tao Yu, Yinong Liu, Xuan Lu, Wenzhe Chen, Lixing Zhou, Yuejie Xu, Min Yang, Andrew D Miller, Hening Lin.

The transcriptional regulators SMAD2 and SMAD3 share the same primary signaling pathway in response to the cytokine TGFβ. However, whereas SMAD2 stimulates the differentiation of naive CD4+ T cells into proinflammatory T helper 17 cells (TH17 cells), SMAD3 stimulates the differentiation of anti-inflammatory regulatory T cells (Treg cells). Here, we report a dynamic SMAD2-specific posttranslational modification important for TH17 cell differentiation. SMAD2, but not SMAD3, was reversibly S-palmitoylated at cysteine-41 and cysteine-81 by the palmitoyltransferase DHHC7 and depalmitoylated by the acyl protein thioesterase APT2. As a result, SMAD2 was recruited to intracellular membranes where its linker region was phosphorylated, leading to its interaction with the transcriptional regulator STAT3. Nuclear translocation of the SMAD2-STAT3 complex induced the expression of their target genes that promoted TH17 cell differentiation. Perturbation of SMAD2-STAT3 binding by inhibiting the palmitoylation-depalmitoylation cycle suppressed TH17 cell differentiation and reduced disease severity in mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis (MS). Thus, the S-palmitoylation-depalmitoylation cycle mediated by DHHC7 and APT2 specifically regulates SMAD2, providing insights into the functional differences between SMAD2 and SMAD3 and the distinct role of SMAD2 in TH17 cell differentiation. The findings further highlight DHHC7 and APT2 as potential therapeutic targets for the treatment of TH17 cell-mediated inflammatory diseases, including MS.

DOI: https://doi.org/10.1126/scisignal.adr2008
Genes Immun. 2025 May 24.

Integrative multi-omics reveal NSUN2 facilitates glycolysis and histone lactylation-driven immune evasion in renal carcinoma.

Kunpeng Wang, Fanyi Kong, Xue Han, Yunlai Zhi, Hai Wang, Chuanli Ren, Hui Wang.

Clear cell renal carcinoma (ccRCC) is the most prevalent and aggressive subtype of kidney cancer. Targeting ccRCC metabolism is a promising therapeutic strategy, and some metabolic targets are currently undergoing clinical trials. Here, we collected multiple ccRCC clinical cohorts, including bulk RNA sequencing and single-cell sequencing datasets, to investigate mitochondrial metabolic genes' prognostic and therapeutic potential. Integrating 10 machine learning algorithms, we constructed 117 predictive models, with the optimal model selected and defined as Mitoscore for patient stratification and treatment. Furthermore, NSUN2, an RNA 5-methylcytosine (m5C) methyltransferase, was identified as the most important gene in the model and selected for further gene function experiments in vitro and in vivo. NSUN2 promoted cell proliferation, migration, and invasion; reprogrammed glycolysis metabolism and histone lactylation levels via maintaining NEO1 mRNA stability. In addition, NSUN2 increased PD-L1 expression in tumor cells via the MYC/POM121/CD274 axis in a lactylation-dependent manner. Knockdown of NSUN2 enhanced CD8 T cell killing effects in vitro, along with TNF-α + T cell infiltration in vivo. These results highlight that mitochondrial genes are optional therapeutic targets and prognostic markers; NSUN2 promotes mitochondrial glycolysis and histone lactylation in an m5C-dependent manner, thereby resulting in PD-L1-mediated immune escape, which elucidates novel NSUN2-mediated crosstalk between glycolysis and immune evasion.

DOI: https://doi.org/10.1038/s41435-025-00336-4
Biol Direct. 2025 May 26. 20(1): 64

LDHA-mediated YAP lactylation promotes the tumor progression of hepatocellular carcinoma by inducing YAP dephosphorylation and activation.

Xiaoyong Wei, Long Zou, Yanqing Huang, Chuan Qiu, Guang Cheng, Ye Chen, Jun Rao.

   BACKGROUND: Hepatocellular carcinoma (HCC) is among the deadliest cancers globally. Yes-Associated Protein (YAP), a Hippo pathway effector, crucially regulates cell proliferation and apoptosis. Recent research has implicated YAP's role in HCC progression, but the mechanisms are unclear. This study aims to clarify YAP's function in HCC, emphasizing its regulation of key pathways and targets.
RESULTS: Gene knockout and overexpression models were established in nude mice and cell lines of HCC cells to investigate YAP's impact on tumorigenesis. Additionally, functional assays and molecular biology techniques were employed to identify YAP's regulatory networks. The study demonstrates that LDHA-regulated lactate production promotes YAP activation and malignant phenotypes in HCC. Overexpression of LDHA in HepG2 and Huh7 cells increased lactate levels and activated the YAP pathway, enhancing cell proliferation, migration, and invasion. Lactate treatment also promoted these malignant phenotypes by inhibiting YAP phosphorylation at Ser127. In a xenograft model, lactate accelerated tumor growth through YAP activation. YAP lactylation at K102 antagonized its Ser127 phosphorylation, further promoting malignant progression.
CONCLUSIONS: This study highlights the significance of YAP in HCC pathogenesis, providing insights into potential therapeutic targets for HCC management.

Keywords:  HCC; Lactylation; Phosphorylation; Poor prognosis; YAP

DOI:  https://doi.org/10.1186/s13062-025-00655-6
Discov Oncol. 2025 May 26. 16(1): 929

Post-translational modifications and the reprogramming of tumor metabolism.

Yuqing Hu, Wenxia Xu, Lin Chen.

  Metabolic reprogramming occurs alongside tumor development. As cancers advance from precancerous lesions to locally invasive tumors and then to metastatic tumors, metabolic patterns exhibit distinct changes, including mutations in metabolic enzymes and modifications in the activity of metabolic regulatory proteins. Alterations in metabolic patterns can influence tumor evolution, either establishing or alleviating metabolic burdens and facilitating cancer growth. To fully understand how metabolic reprogramming helps tumors grow and find the metabolic activities that are most useful for treating tumors, we need to have a deeper understanding of how metabolic patterns are controlled as tumors grow. Post-translational modifications (PTMs), a critical mechanism in the regulation of protein function, can influence protein activity, stability, and interactions in several ways. In tumor cells, PTMs-mediated metabolic reprogramming is a crucial mechanism for adapting to the challenging microenvironment and sustaining fast growth. This article will deeply explore the intricate regulatory mechanism of PTMs on metabolic reprogramming and its role in tumor progression, with the expectation of providing new theoretical basis and potential targets for tumor treatment.

Keywords:  Cancer metabolic; Post-translational modifications; Tumor metabolic reprogramming

DOI:  https://doi.org/10.1007/s12672-025-02674-1
Biomolecules. 2025 May 12. pii: 702. [Epub ahead of print]15(5):

Post-Translational Modifications in Multiple Myeloma: Mechanisms of Drug Resistance and Therapeutic Opportunities.

Shuoyang Hu, Jirun Xu, Weiyan Cui, Haoran Jin, Xiaoyu Wang, Yasen Maimaitiyiming.

  Multiple myeloma (MM) remains an incurable hematologic malignancy due to the inevitable development of drug resistance, particularly in relapsed or refractory cases. Post-translational modifications (PTMs), including phosphorylation, ubiquitination, acetylation, and glycosylation, play pivotal roles in regulating protein function, stability, and interactions, thereby influencing MM pathogenesis and therapeutic resistance. This review comprehensively explores the mechanisms by which dysregulated PTMs contribute to drug resistance in MM, focusing on their impact on key signaling pathways, metabolic reprogramming, and the tumor microenvironment. We highlight how PTMs modulate drug uptake, alter drug targets, and regulate cell survival signals, ultimately promoting resistance to PIs, IMiDs, and other therapeutic agents. Furthermore, we discuss emerging therapeutic strategies targeting PTM-related pathways, which offer promising avenues for overcoming resistance to treatment. By integrating preclinical and clinical insights, this review underscores the potential of PTM-targeted therapies to enhance treatment efficacy and improve patient outcomes in MM.

Keywords:  drug resistance; immunomodulatory drugs (IMiDs); multiple myeloma; post-translational modifications; proteasome inhibitors (PIs); signaling pathways; therapeutic targets; tumor microenvironment

DOI:  https://doi.org/10.3390/biom15050702
Mamm Genome. 2025 May 24.

Glycosylated protein-related microenvironmental features in breast cancer are associated with patient prognosis.

Xiaoxiao Zhong, Jiaxuan Han, Huan Li, Xiangyu Shen, Bowen Yu, Ting Chen, Haobing Li, Jun Li, Jin Pang, Liyuan Qian, Wei Wu, Xiaoliang Tong, Boni Ding.

  The tumor microenvironment (TME) and aberrant glycosylation have been suggested to play key roles in cancer. This study integrated differentially expressed genes (DEGs) and weighted gene coexpression network analysis (WGCNA) to identify tumor microenvironment-related genes and construct a TME-risk prognostic signature (TMERS) through LASSO Cox regression. After batch effect removal, 44 TME-prognosis-related genes (TMEPGs) were identified and classified into three molecular subtypes via K-means clustering. The finalized 22-gene TMERS model demonstrated robust prognostic predictive capacity in GEO datasets. The results revealed distinct immune profiles and prognostic stratifications among genetic subtypes and risk groups, confirming that the TMERS is an independent prognostic indicator for breast cancer (BRCA). Glycosyltransferase genes (GTs) have potential therapeutic relevance through immune regulation, with TMEPG member killer cell lectin like receptor B1 (KLRB1) significantly correlated with BRCA prognosis. Cellular experiments demonstrated that KLRB1 overexpression suppressed BRCA cell proliferation and migration. This work establishes a novel prognostic model for BRCA while highlighting KLRB1 as a potential biomarker, providing new insights into TME-targeted therapeutic strategies.

Keywords:  Breast cancer; Glycosylation; Glycosyltransferases; KLRB1; Prognostic mode; Tumor microenvironment

DOI:  https://doi.org/10.1007/s00335-025-10137-9
Mol Cell Biochem. 2025 May 28.

GPR55 senses lactate to sustain motility in prostate cancer cells.

Giovanna Sgrignani, Marta Iozzo, Lara Di Leonardo, Elisa Pardella, Erica Pranzini, Giulia Gangarossa, Giuseppina Comito, Luigi Ippolito, Elisa Giannoni, Paola Chiarugi.

  The enrichment of specific metabolites within the tumor microenvironment is emerging as a driver of tumor progression. Specifically, in prostate cancer (PCa), increased abundance of lactate is associated with primary-to-metastasis tumor spreading by supporting cancer cell invasiveness. Here, we highlight that the endocannabinoid receptor GPR55 is able to sense lactate and consequently trigger PCa cell amoeboid-like invasiveness, through the activation of the pro-migratory RhoA/MLC2 signaling pathway. These findings uncover a new role for GPR55 in sustaining lactate-driven PCa cell motility.

Keywords:  Amoeboid motility; GPR55; Lactate; Prostate cancer

DOI:  https://doi.org/10.1007/s11010-025-05312-0
Oncol Lett. 2025 Jul;30(1): 350

Comprehensive analysis of a palmitoylation-related prognostic signature in colorectal cancer: Implications for immune therapy and personalized treatment.

Xiaokang Wang, Jian Li, Zi Wang, Qingyun Wu.

  Colorectal cancer (CRC) remains one of the leading causes of cancer-associated mortality worldwide. While immune checkpoint inhibitors have shown promise in treatment, there is a need for reliable biomarkers to predict patient prognosis and guide personalized therapies. Palmitoylation, a post-translational modification, has been implicated in various cancer processes, yet its role in CRC prognosis remains unclear. Transcriptome, survival, somatic mutation and copy number variation data were retrieved from The Cancer Genome Atlas, and the GSE17538 dataset was used for external validation. A palmitoylation-related risk signature was developed using univariate Cox regression, Least Absolute Shrinkage and Selection Operator and multivariate Cox regression analyses. Patients were stratified into high- and low-risk groups based on the median risk score. Prognostic accuracy was assessed using receiver operating characteristic curves and Kaplan-Meier overall survival (OS) analysis with validation in an independent cohort. Functional enrichment, immune cell infiltration and drug sensitivity analyses were performed to explore underlying mechanisms and therapeutic implications. Subsequently, keratin 8 pseudogene 12 (KRT8P12) overexpression was evaluated in HT29 cells, and knockdown HT29 cell lines were generated using lentivirus. Cell proliferation was assessed using Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays, cell migration was evaluated by Transwell assay and cell apoptosis was assessed using Annexin-V/propidium iodide staining. A palmitoylation-related risk signature consisting of six genes (KRT8P12, ZDHHC3, PCOLCE2, MPP2, LARS2 and MMAA) was identified. High-risk patients exhibited significantly worse OS (HR=3.19; P<0.001) compared with low-risk patients. Immune cell infiltration analysis revealed enhanced immune activity in the low-risk group, which was associated with higher expression of immune checkpoint genes. Immunotherapy prediction models indicated that low-risk patients might benefit more from immune checkpoint inhibitors. Drug sensitivity analysis identified distinct drug response profiles between the high- and low-risk groups. Furthermore, in vitro, KRT8P12 promoted tumor cell proliferation and migration while inhibiting apoptosis. In conclusion, the present study confirmed the role of KRT8P12 as a palmitoylation-related gene in regulating CRC. In addition, the palmitoylation-associated risk signature may offer a promising tool for prognostic prediction in CRC and could guide personalized treatment strategies, including immune checkpoint inhibitors and targeted therapies.

Keywords:  CRC; immune cell infiltration; immunotherapy; palmitoylation; prognostic signature

DOI:  https://doi.org/10.3892/ol.2025.15096
Front Immunol. 2025 ;16 1587867

Research trends on lactate in cancer: a bibliometric analysis and comprehensive review (2015-2024).

Sinong Li, Ziyi Yang, Mutian Lv, Lin Zong, Yihan Xie, Zoujuan Cai, Ying Zhang, Zhongqing Wang, Zhe Liu, Liang Sang.

   Objective: A bibliometric approach was employed to systematically analyze the trends and potential future developments in lactic acid-related cancer research over the past 10 years.
Method: We conducted a bibliometric analysis of literature on lactic acid in cancer research from 2015 to 2024, using data collected from the Web of Science database. A bibliometric analysis was conducted to identify general research directions and trends in current publications, as well as to determine the most prolific and influential authors, institutions, countries, and keywords in lactate and cancer research. The data were collected and analyzed using VOSviewer (Leiden University, Leiden, Netherlands), Microsoft Excel (Microsoft, Redmond, Washington, USA), CiteSpace, and Biblioshiny, with a focus on analysis and visualization.
Results: A total of 5,999 publications were analyzed, focusing on various aspects of the relevant literature, including year of publication, country, institution, author, journal, category, keywords, and research frontiers. The analysis of these publications reveals a general upward trend in publication volume from 2015 to 2024, with China and University of California System emerging as the most prolific country and institution, respectively. SCIENTIFIC REPORTS is the most frequently published journal, while Oncotarget is the most cited journal in the field. Zhang Y. was the most prolific author, publishing 100 documents over 10 years, with the highest citation count and an H-index of 28.Keyword analysis revealed five key themes in lactate-cancer research (2013-2023): Metabolic-epigenetic crosstalk, Tumor immunosuppressive microenvironment, Innovative therapies/drug delivery, Lactate-mediated signaling, Metabolic-targeted treatment strategies. Current research emphasizes the application of lactic acid metabolism in metabolic intervention, immune microenvironment regulation, combination of new therapeutic techniques and applications in specific cancer types.
Conclusion: Research on lactic acid in cancer is growing rapidly, with China at the forefront of this field. Research into lactic acid's role in immune cell regulation, metabolism, and signaling pathways, combined with multi-modal imaging, big data analytics, and innovative drug delivery, is set to become a key trend in future studies, which promises new directions for identifying therapeutic targets, biomarkers, and developing advanced treatments.

Keywords:  CiteSpace; VOSviewer; bibliometric analysis; cancer; lactic acid

DOI:  https://doi.org/10.3389/fimmu.2025.1587867
Food Res Int. 2025 Aug;pii: S0963-9969(25)00909-3. [Epub ahead of print]213 116571

Exploring succinylation in proteins: A comprehensive review from functional improvements to application potential.

Weizhuo Zhu, Liping Sun, Ying Gu, Yongliang Zhuang, Xuejing Fan, Yangyue Ding.

  As global populations grow and economic levels rise, the demand for high-quality proteins and their products is increasing. However, natural proteins generally suffer from poor solubility, low thermal stability, limited emulsifying and foaming properties, and undesirable flavors, severely restricting their industrial application. Succinylation, a chemical modification method involving the introduction of succinyl groups onto specific amino acid residues (particularly lysine), has shown considerable promise in improving protein functionalities. This review systematically summarizes recent research advances in protein succinylation, thoroughly discussing key factors affecting reaction efficiency, such as pH, temperature, reaction time, reagent concentration, amino acid composition, and protein structure. Moreover, the review analyzes the influence of succinylation on protein secondary and tertiary structures and resultant changes in solubility, emulsification, foaming, and gelation properties. While succinylation generally enhances protein functionality, it may negatively impact specific functional properties in certain proteins. Reasons underlying these functional differences are also discussed. Furthermore, the review explores potential applications of succinylated proteins in food preservation, bioactive compound encapsulation, and drug delivery systems. Finally, key challenges, including precise control over modification degree, insufficient long-term chemical stability, and limited toxicological assessments, are identified. Future research should focus on protein structure-function relationships, optimization of modification conditions, and comprehensive safety evaluations to facilitate broader industrial acceptance and regulatory compliance of succinylation technology.

Keywords:  Functional challenges; Functional properties; Protein sources; Succinylation

DOI:  https://doi.org/10.1016/j.foodres.2025.116571
Int J Oncol. 2025 Jun;pii: 50. [Epub ahead of print]66(6):

Multifaceted roles of lactate dehydrogenase in liver cancer (Review).

Hai Jin, Qian Liu, Jin Li, Siyu Zhao, Biguang Tuo.

  Hepatocellular carcinoma (HCC) has high morbidity and mortality rates, and metabolic reprogramming of HCC cells supports the proliferation and development of tumor cells. Lactate dehydrogenase (LDH), a key metabolic enzyme, can maintain the rapid proliferative demand of tumor cells by promoting glycolysis and lactate production in HCC cells. In addition, LDH regulates redox homeostasis and influences lipid synthesis and signaling pathways, further promoting tumor invasion and metastasis. In the tumor microenvironment, LDH affects the function of immune cells and stromal cells by regulating the lactate concentration in and promoting the immune escape and angiogenesis of tumor cells. Since elevated levels of LDH are closely associated with tumor load, invasiveness and poor prognosis, LDH also has promising applications in the early diagnosis, treatment and prognostic assessment of HCC. The present study reviewed the roles of LDH in the occurrence, development, diagnosis, prognosis and treatment of HCC and explored its value as an important biomarker and potential therapeutic target, with the aim of providing a comprehensive reference for HCC‑related research and clinical practice.

Keywords:  hepatocellular carcinoma; lactate dehydrogenase; lactic acidification; metabolic reprogramming; tumor microenvironment

DOI:  https://doi.org/10.3892/ijo.2025.5756