Cancer‐Associated Fibroblast‐Induced Remodeling of Tumor Microenvironment in Recurrent Bladder Cancer DOI Creative Commons
Ting Liang,

Tao Tao,

Kai Wu

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(31)

Published: Sept. 24, 2023

Bladder carcinoma (BC) recurrence is a major clinical challenge, and targeting the tumor microenvironment (TME) promising therapy. However, relationship between individual TME components, particularly cancer-associated fibroblasts (CAFs), unclear. Here, heterogeneity in primary recurrent BC investigated using single-cell RNA sequence profiling of 62 460 cells. Two cancer stem cell (CSC) subtypes are identified BC. An inflammatory CAF subtype, ICAM1+ iCAFs, specifically associated with also identified. iCAFs found to secrete FGF2, which acts on CD44 receptor rCSC-M, thereby maintaining stemness epithelial-mesenchymal transition. Additionally, THBS1+ monocytes, group myeloid-derived suppressor cells (MDSCs), enriched interacted CAFs. CCL2, binds CCR2 MDSCs. Moreover, elevated STAT3, NFKB2, VEGFA, CTGF levels reshape tumors. CCL2 inhibition an situ mouse model suppressed growth, decreased MDSCs Tregs, fostered immune suppression. The study results highlight role cell-cell crosstalk during identification pivotal signaling factors driving relapse for development novel therapies.

Language: Английский

Paraptosis: a non-classical paradigm of cell death for cancer therapy DOI

Chuncao Xu,

Yifan Lin,

Mu-yang Huang

et al.

Acta Pharmacologica Sinica, Journal Year: 2023, Volume and Issue: 45(2), P. 223 - 237

Published: Sept. 15, 2023

Language: Английский

Citations

28

Single-cell sequencing technology applied to epigenetics for the study of tumor heterogeneity DOI Creative Commons

Yuhua Hu,

Feng Shen, Xi Yang

et al.

Clinical Epigenetics, Journal Year: 2023, Volume and Issue: 15(1)

Published: Oct. 11, 2023

Previous studies have traditionally attributed the initiation of cancer cells to genetic mutations, considering them as fundamental drivers carcinogenesis. However, recent research has shed light on crucial role epigenomic alterations in various cell types present within tumor microenvironment, suggesting their potential contribution formation and progression. Despite these significant findings, progress understanding epigenetic mechanisms regulating heterogeneity been impeded over past few years due lack appropriate technical tools methodologies.The emergence single-cell sequencing enhanced our governing by revealing distinct layers individual (chromatin accessibility, DNA/RNA methylation, histone modifications, nucleosome localization) diverse omics (transcriptomics, genomics, multi-omics) at level. These technologies provide us with new insights into molecular basis intratumoral help uncover key events driving development.This paper provides a comprehensive review emerging analytical experimental approaches omics, focusing specifically epigenomics. capture integrate multiple dimensions cells, thereby features. Additionally, this outlines future trends current limitations.

Language: Английский

Citations

28

Emerging Roles of RNA Methylation in Development DOI
Mengke Wang, Chun‐Chun Gao, Yun‐Gui Yang

et al.

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(23), P. 3417 - 3427

Published: Nov. 15, 2023

More than 170 different types of chemical modifications have been identified on diverse RNA, collectively known as the epitranscriptome. Among them, N6-methyladenine (m6A), 5-methylcytosine (m5C), N1-methyladenine (m1A), and N7-methylguanosine (m7G) ubiquitous post-transcriptional modification are widely involved in regulating metabolic processes such RNA degradation, translation, stability, export, mediating important physiological pathological stress regulation, immune response, development, tumorigenesis. Recently, regulatory role during developmental is getting more attention. Therefore, development low-input even single-cell high-resolution sequencing technologies crucial for exploration roles these biological events trace samples.This account focuses various processes. We describe distribution characteristics modifications, catalytic enzymes, binding proteins, technologies. dynamically reversible, which can be catalyzed by methyltransferases eliminated demethylases. m6A most abundant eukaryote mRNA, mainly concentrated near stop codon, involves metabolism regulation. m5C, another studied modification, has a organisms species, enriched regions downstream translation initiation sites broadly distributes across whole coding sequence (CDS) mammalian mRNAs. m1A, with lower abundance m6A, distributed types, locates 5' untranslated region (5'UTR) mRNA regulates translation. m7G, one common eukaryotes, at cap internal positions RNAs recently gained considerable attention.Thanks to technology, found regulate tumorigenic process, including tumor proliferation, invasion, metastasis modulating oncogenes suppressor genes, affect oocyte maturation embryonic through maternal zygotic genes. m5C related proteins participate plant growth, neural stem cell differentiation dependent manner. m1A also revealed m7G dysregulation neurodevelopmental disorders neurodegenerative diseases.Collectively, we summarized gradually exhibited methylation discussed possibility candidate biomarkers potential therapeutic targets. The technological anticipated major driving force expand our knowledge this field.

Language: Английский

Citations

28

STGNNks: Identifying cell types in spatial transcriptomics data based on graph neural network, denoising auto-encoder, and k-sums clustering DOI
Lihong Peng,

Xianzhi He,

Xinhuai Peng

et al.

Computers in Biology and Medicine, Journal Year: 2023, Volume and Issue: 166, P. 107440 - 107440

Published: Sept. 9, 2023

Language: Английский

Citations

27

Cancer‐Associated Fibroblast‐Induced Remodeling of Tumor Microenvironment in Recurrent Bladder Cancer DOI Creative Commons
Ting Liang,

Tao Tao,

Kai Wu

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(31)

Published: Sept. 24, 2023

Bladder carcinoma (BC) recurrence is a major clinical challenge, and targeting the tumor microenvironment (TME) promising therapy. However, relationship between individual TME components, particularly cancer-associated fibroblasts (CAFs), unclear. Here, heterogeneity in primary recurrent BC investigated using single-cell RNA sequence profiling of 62 460 cells. Two cancer stem cell (CSC) subtypes are identified BC. An inflammatory CAF subtype, ICAM1+ iCAFs, specifically associated with also identified. iCAFs found to secrete FGF2, which acts on CD44 receptor rCSC-M, thereby maintaining stemness epithelial-mesenchymal transition. Additionally, THBS1+ monocytes, group myeloid-derived suppressor cells (MDSCs), enriched interacted CAFs. CCL2, binds CCR2 MDSCs. Moreover, elevated STAT3, NFKB2, VEGFA, CTGF levels reshape tumors. CCL2 inhibition an situ mouse model suppressed growth, decreased MDSCs Tregs, fostered immune suppression. The study results highlight role cell-cell crosstalk during identification pivotal signaling factors driving relapse for development novel therapies.

Language: Английский

Citations

25