NNT-AS1 in CAFs-derived exosomes promotes progression and glucose metabolism through miR-889-3p/HIF-1α in pancreatic adenocarcinoma DOI Creative Commons
Ping Zhang, Qun Wang, Weijun Lu

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 24, 2024

Abstract It is metabolic and signaling crosstalk between stromal cells tumors in the tumor microenvironment, which influences several aspects of formation drug resistance, including reprogramming. Despite considerable findings linking lncRNAs HIF-1-related regulatory networks to cancer cell, little emphasis has been given role communication cancer-associated fibroblasts (CAFs) cells. Previously, we observed that NNT-AS1 was substantially expressed CAFs exosomes, subsequently investigated influence exosomal on glucose metabolism, proliferation, metastasis pancreatic ductal adenocarcinoma (PDAC) Transmission electron microscopy used examine exosomes secreted by PDAC patient-derived CAFs. qRT-PCR evaluate expression NNT-AS1, miR-889-3p, HIF-1. The CAFs-derived cell progression metabolism have identified. Dual luciferase reporter assays examined binding After co-culture CAFs, found they alter metastasis. In cells, CAF-derived lncRNA acted as a molecular sponge for miR-889-3p. Furthermore, HIF-1 could be targeted miR-889-3p controlled NNT-AS1. This study explores mechanism interaction glycolytic remodeling, through regulating miR-889-3p/HIF-1α, also helps discover new clinical treatment targets PDAC.

Language: Английский

Epigenetic regulation of energy metabolism in obesity DOI Creative Commons
Wei Gao, Jiali Liu, Xiang Lü

et al.

Journal of Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 13(7), P. 480 - 499

Published: July 1, 2021

Obesity has reached epidemic proportions globally. Although modern adoption of a sedentary lifestyle coupled with energy-dense nutrition is considered to be the main cause obesity epidemic, genetic preposition contributes significantly imbalanced energy metabolism in obesity. However, variants loci identified from large-scale studies do not appear fully explain rapid increase last four five decades. Recent advancements next-generation sequencing technologies and tissue-specific effects epigenetic factors metabolic organs have advanced our understanding regulation The epigenome, including DNA methylation, histone modifications, RNA-mediated processes, characterized as mitotically or meiotically heritable changes gene function without alteration sequence. Importantly, modifications are reversible. Therefore, comprehensively landscape could unravel novel molecular targets for treatment. In this review, we summarize current knowledge on roles such methylation acetylation, processes regulating metabolism. We also discuss therapeutic agents

Language: Английский

Citations

59
A novel cuproptosis-related lncRNA nomogram to improve the prognosis prediction of gastric cancer DOI Creative Commons
Anqi Feng, Lingnan He, Tao Chen

et al.

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Aug. 29, 2022

Cuproptosis is a copper-triggered modality of mitochondrial cell death and cuproptosis process may play important roles in gastric cancer development. However, little known about cuproptosis-related lncRNAs adenocarcinoma (STAD). This study aimed to investigate the potential prognostic signatures STAD.The Cancer Genome Atlas (TCGA) database were used obtain gene expression profiles, clinicopathological, OS information for STAD. Cuproptosis-related genes collected based on previous studies screened out by co-expression analysis. The nomogram constructed Cox regression analysis with minimum absolute contraction selection operator (lasso) algorithm. In addition, response ICB therapy immune evasion incidence estimated Tumor Immune Dysfunction Exclusion (TIDE) checkpoint expressions associated risk scores also analyzed. correlation CD209 HAVCR2 experimentally testified RT-qPCR, Western Blot, IHC.Patients classified into high-risk low-risk groups score calculated this model. Kaplan-Meier survival curve revealed that group was poor prognosis. Multivariate suggested lncRNA prediction model an independent factor affecting rate. Furthermore, ROC indicates superior traditional clinicopathological features predicting STAD Finally, functional enrichment investigation notably cholesterol metabolism functions, RT-qPCR Blotting demonstrated relationship LINC01150 HAVCR2.A novel signature impacts prognosis immunological GC.

Language: Английский

Citations

39
The Crucial Role of AR-V7 in Enzalutamide-Resistance of Castration-Resistant Prostate Cancer DOI Open Access
Zeyuan Zheng, Jinxin Li,

Yankuo Liu

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(19), P. 4877 - 4877

Published: Oct. 5, 2022

Prostate cancer (PCa) has the second highest incidence of malignancies occurring in men worldwide. The first-line therapy PCa is androgen deprivation (ADT). Nonetheless, most patients progress to castration-resistant prostate (CRPC) after being treated by ADT. As a second-generation receptor (AR) antagonist, enzalutamide (ENZ) current mainstay new endocrine therapies for CRPC clinical use. However, almost all develop resistance during AR antagonist due various mechanisms. At present, ENZ (ENZR) become challenging treatment CRPC. splice variant 7 (AR-V7) refers ligand-independent and constitutively active considered key driver ENZR In this review, we summarize mechanisms biological behaviors AR-V7 contribute novel insights therapy.

Language: Английский

Citations

39
LncTarD 2.0: an updated comprehensive database for experimentally-supported functional lncRNA–target regulations in human diseases DOI Creative Commons

Hongying Zhao,

Xiangzhe Yin,

Haotian Xu

et al.

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 51(D1), P. D199 - D207

Published: Nov. 2, 2022

Abstract An updated LncTarD 2.0 database provides a comprehensive resource on key lncRNA–target regulations, their influenced functions and lncRNA-mediated regulatory mechanisms in human diseases. is freely available at (http://bio-bigdata.hrbmu.edu.cn/LncTarD or https://lnctard.bio-database.com/). was with several new features, including (i) an increased number of disease-associated lncRNA entries, where the current release 8360 419 disease subtypes 1355 lncRNAs; (ii) predicted 3312 out regulations as potential diagnostic therapeutic biomarkers circulating tumor cells (CTCs); (iii) addition 536 new, experimentally supported that modulate properties cancer stem cells; (iv) clinical application section 2894 for application. Importantly, RNA-seq/microarray single-cell web tools customizable analysis visualization tool used to mining both tissue samples CTCs blood samples. The provide annotation from perspectives pan-cancer cancer-specific level. will be useful investigation deregulation disease.

Language: Английский

Citations

39
The epigenetic regulatory mechanisms of ferroptosis and its implications for biological processes and diseases DOI Creative Commons

Molin Yang,

Hanshen Luo,

Xin Yi

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 22, 2023

Abstract Ferroptosis is a form of regulated cell death triggered by the iron‐dependent peroxidation phospholipids. Interactions iron and lipid metabolism factors jointly promote ferroptosis. has been demonstrated to be involved in development various diseases, such as tumors degenerative diseases (e.g., aortic dissection), targeting ferroptosis expected an effective strategy for treatment these diseases. Recent studies have shown that regulation affected multiple mechanisms, including genetics, epigenetics, posttranscriptional modifications, protein posttranslational modifications. Epigenetic changes garnered considerable attention due their importance regulating biological processes potential druggability. There many on epigenetic ferroptosis, histone modifications acetylation methylation), DNA methylation, noncoding RNAs miRNAs, circRNAs, lncRNAs). In this review, we summarize recent advances research mechanisms with description RNA N 6 ‐methyladenosine (m A) methylation included, ferroptosis‐related which provides reference clinical application regulators related

Language: Английский

Citations

36
BPDE exposure promotes trophoblast cell pyroptosis and induces miscarriage by up-regulating lnc-HZ14/ZBP1/NLRP3 axis DOI
Rong Wang,

Xiaole Xu,

Jingjing Yang

et al.

Journal of Hazardous Materials, Journal Year: 2023, Volume and Issue: 455, P. 131543 - 131543

Published: May 6, 2023

Language: Английский

Citations

33
Molecular mechanism of ferulic acid and its derivatives in tumor progression DOI Creative Commons

Xingxun Bao,

Wei Li,

Ruixue Nie Jia

et al.

Pharmacological Reports, Journal Year: 2023, Volume and Issue: 75(4), P. 891 - 906

Published: May 18, 2023

Abstract Cancer is a significant disease that poses major threat to human health. The main therapeutic methods for cancer include traditional surgery, radiotherapy, chemotherapy, and new such as targeted therapy immunotherapy, which have been developed rapidly in recent years. Recently, the tumor antitumor effects of active ingredients natural plants attracted extensive attention. Ferulic acid (FA), (3-methoxy-4-hydroxyl cinnamic), with molecular formula C 10 H O 4 , phenolic organic compound found ferulic, angelica, jujube kernel, other Chinese medicinal but also, abundant rice bran, wheat food raw materials. FA has anti-inflammatory, analgesic, anti-radiation, immune-enhancing also shows anticancer activity, it can inhibit occurrence development various malignant tumors, liver cancer, lung colon breast cancer. cause mitochondrial apoptosis by inducing generation intracellular reactive oxygen species (ROS). interfere cell cycle cells, arrest most cells G 0 /G 1 phase, exert an effect autophagy; inhibiting migration, invasion, angiogenesis; synergistically improving efficacy chemotherapy drugs reducing adverse reactions. acts on series extracellular targets involved regulation signaling pathways, including phosphatidylinositol 3 kinase (PI3K)/protein B (AKT), B-cell lymphoma-2 (Bcl-2), protein 53 (P53) pathways pathways. In addition, derivatives nanoliposomes, platforms drug delivery, important regulatory resistance. This paper reviews mechanisms therapies provide theoretical support insight clinical therapy.

Language: Английский

Citations

30
LncRNA‐CCAT5‐mediated crosstalk between Wnt/β‐Catenin and STAT3 signaling suggests novel therapeutic approaches for metastatic gastric cancer with high Wnt activity DOI Creative Commons
Chenchen Liu,

Aiwen Shen,

Junquan Song

et al.

Cancer Communications, Journal Year: 2023, Volume and Issue: 44(1), P. 76 - 100

Published: Nov. 27, 2023

Abstract Background Although the constitutively activated Wnt/β‐catenin signaling pathway plays vital roles in gastric cancer (GC) progression, few Wnt inhibitors are approved for clinical use. Additionally, significance of long non‐coding RNAs (lncRNAs) GC intraperitoneal dissemination (IPD) remains elusive. Here, we investigated function and therapeutic potential Wnt‐transactivated lncRNA, colon cancer‐associated transcript 5 (CCAT5), metastasis. Methods LncRNA‐sequencing assay was performed to document abundance changes lncRNAs induced by family member 3A (Wnt3a) degradation‐resistant β‐catenin (S33Y mutated) ascites‐derived cells with low activity. Luciferase reporter, Chromatin immunoprecipitation (ChIP)‐re‐ChIP assays were determine how CCAT5 transcribed. The examined 2 cohorts patients. biological through gain‐ loss‐of‐function studies. molecular mechanism explored RNA‐sequencing, mass spectrometry, CRISPR/Cas9‐knocknout system. RNAi‐based cell xenograft model patient‐derived (PDX) IPD. Results We identified a novel Wnt‐regulated CCAT5, which transactivated β‐catenin/transcription factor 3 (TCF3) complex. significantly upregulated predicted poor prognosis. Functional studies confirmed promotive role growth Mechanistically, bound C‐end domain signal transducer activator transcription (STAT3) blocks Src homology domain‐containing protein tyrosine phosphatase 1 (SHP‐1)‐mediated STAT3 Y705 dephosphorylation, leading nuclear entry transactivation, thus accelerating progression. Furthermore, demonstrated that both Wnt3a acted as pathway, interplay between functionally essential Wnt‐drived tumor evolution. Finally, revealed vivo si‐CCAT5 selectively attenuated metastasis high GC, but not GC. combination oxaliplatin displayed obvious synergistic effects on PDX mice. Conclusions CCAT5. Our study regulation via canonical functional critical mediator. provided conceptual advance serve targets reversing

Language: Английский

Citations

25
LncRNA CCAT1 facilitates the progression of gastric cancer via PTBP1-mediated glycolysis enhancement DOI Creative Commons
Cong Zhang, Huixia Wang, Qingwei Liu

et al.

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

Published: Sept. 23, 2023

Gastric cancer (GC) is one of the most prevalent malignant tumors digestive system. As a hallmark cancer, energy-related metabolic reprogramming manipulated by multiple factors, including long non-coding RNAs (lncRNAs). Notably, lncRNA CCAT1 has been identified as crucial regulator in tumor progression. Nevertheless, precise molecular mechanisms underlying involvement GC remain unclear. Gain- and loss-of-function experiments were performed to evaluate roles tumorigenesis glycolysis GC. Bioinformatics analyses mechanistic experiments, such mass spectrometry (MS), RNA-pulldown, RNA immunoprecipitation (RIP), employed reveal potential interacting protein elucidate regulatory mechanism glycolysis. Moreover, nude mice xenograft assay was used effect on cells vivo. In this study, we that expression significantly elevated tissues plasma exosomes patients, well cell lines. Functional showed knockdown resulted substantial decrease proliferation, migration invasion both vitro vivo through decreasing glycolytic enzymes rate. Conversely, overexpression exhibited contrasting effects. Mechanistically, interacted with PTBP1 effectively maintained its stability inhibiting ubiquitin-mediated degradation process. critical splicing factor, facilitated transition from PKM1 PKM2, thereby augmenting activity ultimately fostering progression Our findings demonstrate plays significant role promoting migration, PTBP1/PKM2/glycolysis pathway, thus suggesting CCAT1's biomarker therapeutic target for

Language: Английский

Citations

24
Beta-elemene: A phytochemical with promise as a drug candidate for tumor therapy and adjuvant tumor therapy DOI Open Access

Yewen Feng,

Qingwen An,

Zhengqi Zhao

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 172, P. 116266 - 116266

Published: Feb. 13, 2024

β-Elemene (IUPAC name: (1 S,2 S,4 R)-1-ethenyl-1-methyl-2,4-bis(prop-1-en-2-yl) cyclohexane), is a natural compound found in turmeric root. Studies have demonstrated its diverse biological functions, including anti-tumor properties, which been extensively investigated. However, these not yet reviewed. The aim of this review was to provide comprehensive summary β-elemene research, with respect disease treatment.

Language: Английский

Citations

13