The LncRNA LENOX Interacts with RAP2C to Regulate Metabolism and Promote Resistance to MAPK Inhibition in Melanoma DOI Creative Commons
Giovanni Gambi, Gabrielle Mengus, Guillaume Davidson

et al.

Cancer Research, Journal Year: 2022, Volume and Issue: 82(24), P. 4555 - 4570

Published: Oct. 10, 2022

Abstract Tumor heterogeneity is a key feature of melanomas that hinders development effective treatments. Aiming to overcome this, we identified LINC00518 (LENOX; lincRNA-enhancer oxidative phosphorylation) as melanoma-specific lncRNA expressed in all known melanoma cell states and essential for survival vitro vivo. Mechanistically, LENOX promoted association the RAP2C GTPase with mitochondrial fission regulator DRP1, increasing DRP1 S637 phosphorylation, fusion, phosphorylation. expression was upregulated following treatment MAPK inhibitors, facilitating metabolic switch from glycolysis phosphorylation conferring resistance inhibition. Consequently, combined silencing synergized inhibitors eradicate cells. Melanomas are thus addicted LENOX, which acts optimize function during progression. Significance: The novel metabolism, can be targeted conjunction

Language: Английский

Small molecule metabolites: discovery of biomarkers and therapeutic targets DOI Creative Commons
Shi Qiu, Ying Cai, Hong Yao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 20, 2023

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks diseases. Metabolite signatures that have close proximity subject's phenotypic informative dimension, are useful for predicting diagnosis prognosis diseases as well monitoring treatments. The lack early biomarkers could poor serious outcomes. Therefore, noninvasive methods with high specificity selectivity desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool biomarker pathway analysis, revealing possible mechanisms human various deciphering therapeutic potentials. It help identify functional related variation delineate biochemical changes indicators pathological damage prior disease development. Recently, scientists established large number profiles reveal underlying networks target exploration in biomedicine. This review summarized analysis on potential value small-molecule candidate metabolites clinical events, may better diagnosis, prognosis, drug screening treatment. We also discuss challenges need be addressed fuel next wave breakthroughs.

Language: Английский

Citations

388
Mitochondrial RNA modifications shape metabolic plasticity in metastasis DOI Creative Commons
Sylvain Delaunay, Gloria Pascual, Bohai Feng

et al.

Nature, Journal Year: 2022, Volume and Issue: 607(7919), P. 593 - 603

Published: June 29, 2022

Aggressive and metastatic cancers show enhanced metabolic plasticity1, but the precise underlying mechanisms of this remain unclear. Here we how two NOP2/Sun RNA methyltransferase 3 (NSUN3)-dependent modifications-5-methylcytosine (m5C) its derivative 5-formylcytosine (f5C) (refs.2-4)-drive translation mitochondrial mRNA to power metastasis. Translation mitochondrially encoded subunits oxidative phosphorylation complex depends on formation m5C at position 34 in tRNAMet. m5C-deficient human oral cancer cells exhibit increased levels glycolysis changes their function that do not affect cell viability or primary tumour growth vivo; however, plasticity is severely impaired as tumours metastasize efficiently. We discovered CD36-dependent non-dividing, metastasis-initiating require activate invasion dissemination. Moreover, a mitochondria-driven gene signature patients with head neck predictive for metastasis disease progression. Finally, confirm switch allows can be pharmacologically targeted through inhibition vivo. Together, our results reveal site-specific modifications could therapeutic targets combat

Language: Английский

Citations

206
Xuanfei Baidu formula alleviates impaired mitochondrial dynamics and activated NLRP3 inflammasome by repressing NF-κB and MAPK pathways in LPS-induced ALI and inflammation models DOI Creative Commons
Zhenhao Li, Haitao Pan, Jihong Yang

et al.

Phytomedicine, Journal Year: 2022, Volume and Issue: 108, P. 154545 - 154545

Published: Nov. 9, 2022

Xuanfei Baidu Formula (XBF) is an effective traditional Chinese medicine (TCM) remedy for treating coronavirus disease 2019 (COVID-19) in China. This herbal has shown effects reducing clinical symptoms and shortening the average length of hospital stay COVID-19 patients. Previous studies have demonstrated that XBF alleviates acute lung injury (ALI) by regulating macrophage-mediated immune inflammation, but mechanisms action remain elusive. study aimed to evaluate lung-protective anti-inflammatory its underlying mechanisms. Here, XBF's were investigated ALI mouse model induced inhalation atomized lipopolysaccharide (LPS). Besides, LPS-induced inflammation RAW264.7 cells was used clarify against ALI. Our results showed treatment alleviated injury, as evidenced reduced histopathological changes, pulmonary alveoli permeability, fibrosis, apoptosis tissues. In addition, decreased levels tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β serum bronchoalveolar lavage fluid (BALF), white blood cell (WBC) count BALF. Furthermore, consistent with vivo assay, inhibited inflammatory cytokines release pro-inflammatory polarization cells. Mechanistically, increased mitochondrial fusion upregulating Mfn1 attenuated NLRP3 inflammasome activation repressing Casp11, respectively, inhibit NF-κB MAPK pathways, thus macrophage polarization. this study, we demonstrate exerts anti-ALI -inflammatory recovering dynamics activation, providing a biological illustration efficacy

Language: Английский

Citations

78
Hallmarks of cancer stemness DOI Creative Commons

Jia-Jian Loh,

Stephanie Ma

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(5), P. 617 - 639

Published: May 1, 2024

Language: Английский

Citations

71
Mitochondrial dynamics and colorectal cancer biology: mechanisms and potential targets DOI Creative Commons
Zihong Wu, Chong Xiao, Jing Long

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 1, 2024

Colorectal cancer (CRC) is a significant public health concern, and its development associated with mitochondrial dysfunction. Mitochondria can adapt to the high metabolic demands of cells owing their plasticity dynamic nature. The fusion-fission dynamics mitochondria play crucial role in signal transduction functions CRC cells. Enhanced fission promotes reprogramming cells, leading cell proliferation, metastasis, chemoresistance. Excessive also trigger mitochondria-mediated apoptosis. In contrast, excessive fusion leads adenosine triphosphate (ATP) overproduction abnormal tumor whereas moderate protects intestinal epithelial from oxidative stress-induced damage, thus preventing colitis-associated (CAC). Therefore, an imbalance either promote or inhibit progression. This review provides overview mechanism underlying impact on biology. revealed dual identified potential drug targets. Additionally, this study partially explored immune vascular endothelial microenvironment, suggesting promising prospects for targeting key fusion/fission effector proteins against CRC.

Language: Английский

Citations

23
Lactate controls cancer stemness and plasticity through epigenetic regulation DOI Creative Commons

Nguyen T.B. Nguyen,

Sira Gevers,

Rutger N.U. Kok

et al.

Cell Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Tumors arise from uncontrolled cell proliferation driven by mutations in genes that regulate stem renewal and differentiation. Intestinal tumors, however, retain some hierarchical organization, maintaining both cancer cells (CSCs) differentiated (CDCs). This heterogeneity, coupled with cellular plasticity enabling CDCs to revert CSCs, contributes therapy resistance relapse. Using genetically encoded fluorescent reporters human tumor organoids, combined our machine-learning-based tracker, CellPhenTracker, we simultaneously traced cell-type specification, metabolic changes, reconstructed lineage trajectories during organoid development. Our findings reveal distinctive phenotypes CSCs CDCs. We find lactate regulates dynamics, suppressing CSC differentiation inducing dedifferentiation into a proliferative state. Mechanistically, increases histone acetylation, epigenetically activating MYC. Given lactate's regulation of MYC depends on the bromodomain-containing protein 4 (BRD4), targeting metabolism BRD4 inhibitors emerge as promising strategy prevent

Language: Английский

Citations

5
Regulatory roles of mitochondria and metabolism in neurogenesis DOI Creative Commons
Ryohei Iwata, Pierre Vanderhaeghen

Current Opinion in Neurobiology, Journal Year: 2021, Volume and Issue: 69, P. 231 - 240

Published: June 23, 2021

Neural stem cells (NSCs) undergo massive molecular and cellular changes during neuronal differentiation. These include mitochondria metabolism remodelling, which were thought to be mostly permissive cues, but recent work indicates that they are causally linked neurogenesis. Striking remodelling of occurs right after mitosis NSCs, influences the postmitotic daughter towards self-renewal or The transitioning fate requires metabolic rewiring including increased oxidative phosphorylation activity, drives transcriptional epigenetic effects influence cell fate. Mitochondria pathways also contribute in an essential way regulation NSC proliferation self-renewal. on neurogenesis is conserved from fly human systems, displays striking differences context species. new findings have important implications for our understanding neurodevelopmental diseases possibly brain evolution.

Language: Английский

Citations

88
Metabolic determinants of tumour initiation DOI
Julia Brunner, Lydia W.S. Finley

Nature Reviews Endocrinology, Journal Year: 2022, Volume and Issue: 19(3), P. 134 - 150

Published: Nov. 29, 2022

Language: Английский

Citations

47
Light-activated mitochondrial fission through optogenetic control of mitochondria-lysosome contacts DOI Creative Commons
Kangqiang Qiu, Weiwei Zou,

Hongbao Fang

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 25, 2022

Abstract Mitochondria are highly dynamic organelles whose fragmentation by fission is critical to their functional integrity and cellular homeostasis. Here, we develop a method via optogenetic control of mitochondria–lysosome contacts (MLCs) induce mitochondrial with spatiotemporal accuracy. MLCs can be achieved blue-light-induced association mitochondria lysosomes through various photoactivatable dimerizers. Real-time induction tracked in living cells measure the rate. The partially restores functions SLC25A46 −/− cells, which display defects hyperfused mitochondria. system thus provides platform for studying treating diseases.

Language: Английский

Citations

43
Crosstalk between oxidative phosphorylation and immune escape in cancer: a new concept of therapeutic targets selection DOI

Xutong Qiu,

Yi Li, Zhuoyuan Zhang

et al.

Cellular Oncology, Journal Year: 2023, Volume and Issue: 46(4), P. 847 - 865

Published: April 11, 2023

Language: Английский

Citations

30