bims-cesirm 2025-06-08 papers

Issue of 2025–06–08
four papers selected by
Tigist Tamir, University of North Carolina

Pharmacol Res. 2025 May 30. pii: S1043-6618(25)00226-9. [Epub ahead of print]217 107801

Post-translational modifications of RGS protein family: Pivotal switches in cellular signaling transduction and diseases.

Yan Song, Zihao An, Jiepu Wang, Qiang Xu, Jiayong Li, Chao Tang.

Regulator of G protein signaling (RGS) proteins are critical modulators of G protein-coupled receptor (GPCR) signaling through their GTPase-activating protein (GAP) activity. RGS proteins are regulated at multiple levels, including the pre-transcription, transcription, and post-translation levels. Among the regulation patterns, post-translational modification (PTMs) can directly affect the regulation of G protein signaling by modulating the GAP activity of RGS proteins or indirectly regulate their function by affecting their subcellular localization and stability. The corresponding PTM behavior of a certain RGS protein is regulated by complex upstream factors and is closely related to multiple downstream signal transduction associated with G proteins. This complex regulatory relationship forms a dynamic and fine-tuned regulatory network within the cell. In this review, we methodically summarize the impact of diverse PTMs on RGS proteins and provide a comprehensive overview of their associated upstream regulatory factors and downstream signal pathway alterations. Furthermore, we explore the physiological and pathological states associated with PTM dysregulation. Additionally, we discuss the potential clinical application value of PTMs targeting RGS.

Keywords: Cell signaling; Clinical application; Disease mechanism; PTMs; RGS

DOI: https://doi.org/10.1016/j.phrs.2025.107801

Front Immunol. 2025 ;16 1582166

Crosstalk between metabolic reprogramming and microbiota: implications for cancer progression and novel therapeutic opportunities.

Xingchen Li, Yidi Jia, Yanqing Li, Hu Hei, Songtao Zhang, Jianwu Qin.

Metabolic reprogramming is a process by which cells adapt to the nutrient microenvironment by regulating energy metabolism. Compared with normal cells, tumor cells tend to undergo metabolic reprogramming, which is one of the hallmarks of concurrent genomic instability, and immune evasion in tumor cells. The microbial community, known as "second genome" of human beings, can cause systemic disease by predisposing cells to tumors, and modulating immune responses to cancer. Metabolic reprogramming and microorganisms can crosstalk with each other in multiple ways to influence various physiological and pathological responses in cancer progression. The products of increased synthesis by tumor cells can reach the intestinal tract via the circulation and act on the microorganisms, promoting mucosal inflammation, causing systemic disorders, and may also regulate the immune response to cancer. In addition, the metabolites of the microorganisms can in turn be transported to the tumor microenvironment (TME) through the systemic circulation and participate in the process of tumor metabolic reprogramming. Different molecular mechanisms related to metabolic reprogramming and microbiota imbalance control the outcome of tumor or anti-tumor responses, depending on the type of cancer, stage of the disease and the TME. In this review, we focus on the fundamental role of metabolic reprogramming in the interaction between microorganisms and cancers and explore the molecular mechanisms by which metabolic reprogramming modulates this complex biological process. This comment aims to provide valuable resources for clinicians and researchers and promote further research in the field.

Keywords: anti-tumor therapy; cancer progression; metabolic reprogramming; microbiota; tumor microenvironment

DOI: https://doi.org/10.3389/fimmu.2025.1582166

J Proteome Res. 2025 Jun 06.

3-Hydroxybutyrate Suppresses Colon Cancer Growth by Inducing Intracellular Lactate Accumulation and Oxidative Stress.

Xu Qiu, Wenfang Wu, Zhiyun Zou, Caihua Huang, Donghai Lin.

Cancer cachexia (CAC) remains a significant hurdle in the treatment of colon cancer, often resulting in poor clinical outcomes. This study explores the therapeutic potential of 3-hydroxybutyrate (3-HB) in the treatment of colon CAC by assessing its effects on tumor growth and cellular metabolism in a colon CAC mouse model and CT26 colon cancer cells. Using NMR-based metabolomics and molecular biology techniques, we show that 3-HB significantly suppresses tumor growth in CAC mice, possibly through lactate accumulation in tumor tissue and modulation of key metabolic pathways. Notably, this treatment leads to a paradoxical increase in intracellular lactate levels within tumor cells, accompanied by a decrease in extracellular lactate in the tumor microenvironment, due to 3-HB competing with lactate for monocarboxylate transporters (MCTs). Furthermore, 3-HB increases oxidative stress and induces apoptosis in CT26 cells, as evidenced by increased levels of reactive oxygen species (ROS) and caspase-3 activation. Mechanistically, 3-HB competes with lactate for monocarboxylate transporters (MCTs), resulting in intracellular lactate accumulation, acidification, and subsequent tumor suppression. These findings highlight the potential of 3-HB as a viable candidate for CAC therapy and provide new insights into metabolic reprogramming strategies in cancer treatment.

Keywords: 3-hydroxybutyrate; cell acidification; colon cancer; lactate; metabolomic profiling; monocarboxylate transporters

DOI: https://doi.org/10.1021/acs.jproteome.4c00991

Cell Biosci. 2025 Jun 05. 15(1): 79

Post-translational modifications in the pathophysiological process of metabolic dysfunction‑associated steatotic liver disease.

Yiyang Min, Yiqiao Zhang, Yu Ji, Shanshan Liu, Chengjian Guan, Luyang Wei, Huajing Yu, Zhongtao Zhang.

In recent years, the prevalence of metabolic dysfunction‑associated steatotic liver disease (MASLD), which was called non-alcoholic fatty liver disease (NAFLD), has been progressively increasing in populations. The progression of MASLD encompasses a spectrum from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), and ultimately to cirrhosis or even hepatocellular carcinoma. During the early stages of the disease, lipid accumulation and endoplasmic reticulum stress may lead to abnormalities in hepatic DNA expression, protein synthesis, and post-translational modifications (PTMs). PTMs play a crucial role in the progression of MASLD and include histone and non-histone modifications, with major types including methylation, acetylation, ubiquitination, and phosphorylation. Numerous studies indicate that within MASLD-related signaling pathways, PTMs can modulate protein activity, localization, folding, and interactions by altering their physicochemical properties. This review summarizes various significant PTMs involved in MASLD progression to elucidate the regulatory mechanisms and pathogenesis associated with the disease.

Keywords: Histone protein; Metabolic dysfunction‑associated steatotic liver disease (MASLD); Non-histone protein; Post-translational modifications (PTMs)

DOI: https://doi.org/10.1186/s13578-025-01411-z