Novel Implication of the Basement Membrane for Breast Cancer Outcome and Immune Infiltration DOI Creative Commons
W. H. Tian,

Yongzhou Luo,

Yuhui Tang

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(5), P. 1645 - 1663

Published: Jan. 1, 2023

Therapeutic failure in breast cancer patients is largely attributed to postoperative advancement and therapy resistance.Nevertheless, an efficacious prognostic signature for recognizing this population lacking.The basement membrane (BM) has been proven be strongly involved progression metastasis, the potential a powerful predictor cancer.In study, substantial bulk RNA transcriptomics, single cell transcriptomics clinical information were collected from TCGA-BRCA, METABRIC GSE96058, Kaplan-Meier survival curves, analysis vitro experiments conducted validate signature.From results, index, namely, BMscore, was established with six pivotal BM genes, specifically LOXL1, FBLN1, FBLN5, SDC1, ADAMTS8 PXDNL.Verification by independent cohorts showed that high BMscore had distinctly worse outcome.By integrating factors, we constructed nomogram displayed good predictive capability.Furthermore, evaluated implication of immune infiltration.More importantly, positive correlation between EMT activity revealed immunohistochemistry experiments.Taken together, provided novel gene predict prognosis metastasis accurately, which may help individualized decision-making.

Language: Английский

The Single‐Cell Landscape of Intratumoral Heterogeneity and The Immunosuppressive Microenvironment in Liver and Brain Metastases of Breast Cancer DOI Creative Commons
Yutian Zou, Feng Ye, Yanan Kong

et al.

Advanced Science, Journal Year: 2022, Volume and Issue: 10(5)

Published: Dec. 18, 2022

Distant metastasis remains the major cause of morbidity for breast cancer. Individuals with liver or brain have an extremely poor prognosis and low response rates to anti-PD-1/L1 immune checkpoint therapy compared those at other sites. Therefore, it is urgent investigate underlying mechanism resistance develop more effective immunotherapy strategies these patients. Using single-cell RNA sequencing, a high-resolution map entire tumor ecosystem based on 44 473 cells from cancer metastases depicted. Identified by canonical markers confirmed multiplex immunofluorescent staining, metastatic features remarkable reprogramming immunosuppressive such as FOXP3+ regulatory T cells, LAMP3+ tolerogenic dendritic CCL18+ M2-like macrophages, RGS5+ cancer-associated fibroblasts, LGALS1+ microglial cells. In addition, PD-1 PD-L1/2 are barely expressed in CD8+ cancer/immune/stromal respectively. Interactions molecules LAG3-LGALS3 TIGIT-NECTIN2 between found play dominant roles escape. summary, this study dissects intratumoral heterogeneity microenvironment first time, providing insights into most appropriate

Language: Английский

Citations

173
A novel axis of circKIF4A-miR-637-STAT3 promotes brain metastasis in triple-negative breast cancer DOI Creative Commons
Song Wu, Jibu Lu, Hongbo Zhu

et al.

Cancer Letters, Journal Year: 2023, Volume and Issue: 581, P. 216508 - 216508

Published: Nov. 28, 2023

Among patients with triple-negative breast cancer (TNBC), distant metastasis is the leading cause of death. Our previous studies have shown that TNBC progression greatly facilitated by circKIF4A, but uncertainty remains regarding its role in brain and molecular mechanism. In this study, we found notable upregulation circKIF4A cell lines metastases. Inhibition impaired ability to proliferate, migrate, metastasis. Luciferase reporter assays confirmed competed for binding miR-637 STAT3 3’ UTR. Western blot analysis revealed inhibition decreased p62 expression, while increased LC3B-II/LC3B–I ratio expression Beclin, indicating downregulation induced autophagy competing miR-637. By employing a competitive endogenous RNA (ceRNA) mechanism, circKIF4A-miR-637-STAT3 axis coordinates TNBC. can therefore be used as prognostic biomarker therapeutic target.

Language: Английский

Citations

113
Metabolic reprogramming and epigenetic modifications in cancer: from the impacts and mechanisms to the treatment potential DOI Creative Commons
Xuemeng Xu, Peng Qiu,

Xianjie Jiang

et al.

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(7), P. 1357 - 1370

Published: July 3, 2023

Abstract Metabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cells, metabolic pathway activity varies during tumorigenesis progression, indicating regulated plasticity. changes often closely related to changes, such as alterations in the expression or epigenetically modified enzymes, which may exert a direct an indirect influence on cellular metabolism. Therefore, exploring mechanisms underlying regulating tumor cell metabolism is important for further understanding pathogenesis. Here, we mainly focus latest studies regulations, including glucose, lipid amino acid context, then emphasize modifications. Specifically, discuss role played by DNA methylation, chromatin remodeling, noncoding RNAs histone lactylation growth progression. Finally, summarize prospects potential therapeutic strategies based

Language: Английский

Citations

97
Methylation of GPRC5A promotes liver metastasis and docetaxel resistance through activating mTOR signaling pathway in triple negative breast cancer DOI Creative Commons

Xueqi Ou,

Yeru Tan, Jindong Xie

et al.

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 73, P. 101063 - 101063

Published: Feb. 1, 2024

This study aims to explore the function and mechanism of G Protein-coupled receptor class C group 5 member A (GPRC5A) in docetaxel-resistance liver metastasis breast cancer.

Language: Английский

Citations

85
Dissection of FOXO1-Induced LYPLAL1-DT Impeding Triple-Negative Breast Cancer Progression via Mediating hnRNPK/β-Catenin Complex DOI Creative Commons
Yuhui Tang, W. H. Tian, Shaoquan Zheng

et al.

Research, Journal Year: 2023, Volume and Issue: 6

Published: Jan. 1, 2023

Triple-negative breast cancer (TNBC) is considered as the most hazardous subtype of owing to its accelerated progression, enormous metastatic potential, and refractoriness standard treatments. Long noncoding RNAs (lncRNAs) are extremely intricate in tumorigenesis cancerous metastasis. Nonetheless, their roles initiation augmentation TNBC remain elusive. Here, silico analysis validation experiments were utilized analyze expression pattern clinically effective lncRNAs TNBC, among which a protective lncRNA LYPLAL1-DT was essentially curbed samples indicated favorable prognosis. Gain- loss-of-function assays elucidated that considerably attenuated proliferative properties along with epithelial-mesenchymal transition cells. Moreover, forkhead box O1 (FOXO1) validated modulate transcription LYPLAL1-DT. Mechanistically, impinged on malignancy mainly by restraining aberrant reactivation Wnt/β-catenin signaling pathway, explicitly destabilizing diminishing β-catenin protein interacting heterogeneous nuclear ribonucleoprotein K (hnRNPK) constricting formation hnRNPK/β-catenin complex. Conclusively, our present research revealed anti-oncogenic effects unraveling molecular mechanisms FOXO1/LYPLAL1-DT/hnRNPK/β-catenin axis, shed innovative light potential curative medicine TNBC.

Language: Английский

Citations

81
Circular RNAs in breast cancer diagnosis, treatment and prognosis DOI Creative Commons

X. Huang,

Cailu Song,

JINHUI ZHANG

et al.

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Journal Year: 2023, Volume and Issue: 32(2), P. 241 - 249

Published: Dec. 7, 2023

Breast cancer has surpassed lung to become the most common malignancy worldwide. The incidence rate and mortality of breast continue rise, which leads a great burden on public health. Circular RNAs (circRNAs), new class noncoding (ncRNAs), have been recognized as important oncogenes or suppressors in regulating initiation progression. In cancer, circRNAs significant roles tumorigenesis, recurrence multidrug resistance that are mediated by various mechanisms. Therefore, may serve promising targets therapeutic strategies for management. This study reviews recent studies about biosynthesis characteristics diagnosis, treatment prognosis evaluation, well value clinical applications biomarkers cancer. Understanding mechanisms function could help transform basic research into facilitate development novel circRNA-based treatment.

Language: Английский

Citations

57
Lactate in the tumor microenvironment: A rising star for targeted tumor therapy DOI Creative Commons

Zhangzuo Li,

Qi Wang, Xu‐Feng Huang

et al.

Frontiers in Nutrition, Journal Year: 2023, Volume and Issue: 10

Published: Feb. 16, 2023

Metabolic reprogramming is one of fourteen hallmarks tumor cells, among which aerobic glycolysis, often known as the “Warburg effect,” essential to fast proliferation and aggressive metastasis cells. Lactate, on other hand, a ubiquitous molecule in microenvironment (TME), generated primarily by cells undergoing glycolysis. To prevent intracellular acidification, malignant remove lactate along with H + , yet acidification TME inevitable. Not only does highly concentrated within serve substrate supply energy but it also works signal activate multiple pathways that enhance invasion, intratumoral angiogenesis, well immune escape. In this review, we aim discuss latest findings metabolism particularly capacity extracellular influence microenvironment. addition, examine current treatment techniques employing existing medications target interfere generation transport cancer therapy. New research shows targeting metabolism, lactate-regulated action are viable therapy strategies.

Language: Английский

Citations

50
Targeting tumor exosomal circular RNA cSERPINE2 suppresses breast cancer progression by modulating MALT1-NF-𝜅B-IL-6 axis of tumor-associated macrophages DOI Creative Commons
Boxuan Zhou,

Zhaohong Mo,

Guie Lai

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: Feb. 17, 2023

Circular RNAs (circRNAs) have important regulatory functions in cancer, but the role of circRNAs tumor microenvironment (TME) remains unclear. Moreover, we also explore effects si-circRNAs loaded nanoparticles as therapeutic agent for anti-tumor vivo.We conducted bioinformatics analysis, qRT-PCR, EdU assays, Transwell co-culture system and multiple orthotopic xenograft models to investigate expression function circRNAs. Additionally, PLGA-based with were used evaluate potential nanotherapeutic strategy response.We identified oncogene SERPINE2 derived circRNA, named cSERPINE2, which was notably elevated breast cancer closely related poor clinical outcome. Functionally, exosomal cSERPINE2 shuttled associated macrophages (TAMs) enhanced secretion Interleukin-6 (IL-6), leading increased proliferation invasion cells. Furthermore, IL-6 turn EIF4A3 CCL2 levels within cells a positive feedback mechanism, further enhancing biogenesis promoting recruitment TAMs. More importantly, developed nanoparticle si-cSERPINE2, effectively attenuated progression vivo.Our study illustrates novel mechanism that mediates loop between TAMs promote progression, may serve promising treatment cancer.

Language: Английский

Citations

48
Hsa_circ_0060467 promotes breast cancer liver metastasis by complexing with eIF4A3 and sponging miR-1205 DOI Creative Commons
Yan Zeng, Wei Du,

Zhongying Huang

et al.

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: May 9, 2023

Breast cancer (BC) is the most common and top cause of female mortality worldwide. The prognosis for patients with breast liver metastasis (BCLM) remains poor. Emerging studies suggest that circular RNAs (circRNAs) are associated progression BC. Exploration circRNAs presents a promising avenue identifying metastasis-targeting agents improving BCLM. Microarray bioinformatic analyses were used to analyze differentially expressed between three pairs BCLM primary roles hsa_circ_0060467 (circMYBL2) its target gene E2F1 in BC cells explored by multiple functional experiments. And xenograft mouse models hepatic metastases hemi-spleen illustrate function circMYBL2 vivo. intrinsic molecular mechanism involving was confirmed bioinformatics analyses, RIP assays, CHIRP luciferase reporter rescue CircMYBL2 overexpressed tissues cells. Functionally, can facilitate proliferation Mechanistically, upregulated transcription factor sponging miR-1205 complexing eukaryotic translation initiation 4A3 (eIF4A3) then facilitated epithelial-mesenchymal transition (EMT) process Our findings showed promoted tumorigenesis aggressiveness through circMYBL2/miR-1205/E2F1 circMYBL2/eIF4A3/E2F1 axes, which may provide novel targeted therapy

Language: Английский

Citations

48
Lactate drives epithelial-mesenchymal transition in diabetic kidney disease via the H3K14la/KLF5 pathway DOI Creative Commons
Xuanxuan Zhang,

Jicong Chen,

Ruohui Lin

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 75, P. 103246 - 103246

Published: June 20, 2024

High levels of urinary lactate are an increased risk progression in patients with diabetic kidney disease (DKD). However, it is still unveiled how drive DKD. Epithelial-mesenchymal transition (EMT), which characterized by the loss epithelial cells polarity and cell-cell adhesion, acquisition mesenchymal-like phenotypes, widely recognized a critical contributor to Here, we found switch from oxidative phosphorylation (OXPHOS) toward glycolysis AGEs-induced renal tubular cells, thus leading elevated lactic acid. We demonstrated that reducing markedly delayed EMT improved fibrosis Mechanically, observed histone H3 lysine 14 lactylation (H3K14la) Chip-seq & RNA-seq results showed contributed process facilitating KLF5 expression. Moreover, promotor CDH1 inhibited its transcription, accelerated Additionally, nephro-specific knockdown pharmacological inhibition diminished development attenuated DKD fibrosis. Thus, our study provides better understanding epigenetic regulation pathogenesis, new therapeutic strategy for disruption lactate-drived H3K14la/KLF5 pathway.

Language: Английский

Citations

23