Implications of pseudogenes for the prognosis of hepatocellular carcinoma DOI Creative Commons
Zaoqu Liu, Yuyuan Zhang, Siyuan Weng

et al.

Clinical and Translational Medicine, Journal Year: 2023, Volume and Issue: 13(2)

Published: Feb. 1, 2023

Growing evidence has demonstrated that pseudogenes are intricately associated with tumour progression in hepatocellular carcinoma (HCC).1 Nonetheless, related to immune infiltration and their value improving clinical outcomes remain largely unexplored. Pseudogenes, newly discovered non-coding homologs of protein-coding genes,1 have been regarded as non-functional evolutional relics. Nevertheless, increasing play vital roles tumourigenesis regulators coding genes. For example, HMGA1P6, a pseudogene transcriptionally activated by oncogene MYC, could contribute oncogenesis ovarian cancer.2 Besides, also profound impacts on anti-tumour responses via involvement regulating tumour-immune interactions. BRCA1 Pseudogene 1 (BRCA1P1) reported weaken response suppressing innate defense mechanisms.3 Through glioma-derived exosomes, TMEM198B promoted macrophage lipid accumulation increased fatty acid oxidation, further inducing macrophages M2 polarization.4 However, the significance immune-related remains unexplored HCC. Here, we enrolled four public datasets abundant expression profiles complete prognostic information, including: The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) (n = 340), GSE116174 64), GSE144269 67) GSE14520 242) (Table S1). To systematically evaluate candidate intrinsic modulators cells, introduced novel framework identify housekeeping (Supplementary Materials). In TCGA-LIHC, relative abundance 28 cells was first deciphered using ssGSEA algorithm.5 Considering purity may obscure links microenvironment,6 thus calculated first-order partial correlation coefficient (PCC) between removing effect purity.6, 7 Pseudogenes top 5% PCC were extracted for each cell. A hypothesis is if specific strong correlations all cell types, it execute role HCC microenvironment,8 which defined (HIRIP) this study. tissue specificity index (TSI)9 generally correlated different types S2). As previously reported,9 lower TSI score strongly suggesting biological functions immunity. According criteria described previous studies,8, 9 settled threshold <.2 identified 23 HIRIP essential regulation (Figure S1A). Subsequently, filtered develop an integrative signature (HIRIPS). Initially, univariate Cox regression analysis determined potential, including HNRNPA3P5, HNRNPA3P6, PTMAP5 EIF2S2P4 S1B). Kaplan–Meier high these suggested unfavorable prognosis 1A). Afterward, optimal machine-learning algorithm assessing prognosis, developed 22 survival models Materials) based TCGA-LIHC. mentioned above, final HIRIPS fitted Akritas highest average mean C-index (.667) integrated areas under curve (iAUC) (.825) TCGA training cohort three validation cohorts (GSE116174, GSE14520) considered one 1B). validate robust performance HIRIPS, Kaplan-Meier analyses applied. Notably, patients possessed adverse TCGA-LIHC (HR 1.713; log-rank test: P < .001), similar tracks observed datasets, 1.136; 1.120; 1.118; .001) 2A). time-dependent receiver operating characteristic (ROC) curves OS (1-, 2-, 3-year) exhibited excellent discrimination 2B) (AUC values: .728, .690, .699), .714, .751, .700), .703, .704, .714), .691, .694, .702). Multivariate performed remained statistical after adjusting confounding factors across 2C). Overall, presented clear superior predicting prognosis. explore mechanisms underlying proposed pipeline perform functional enrichment, maximized information retention comprehensively gene ordering over-representing revealed predominant enrichment pathways malignant progressions, such cycle p53 signaling 3A Figure Whereas low particularly evident pathways, cytokine activity T receptor another bioinformatics algorithm, GSEA, confirmed significantly linked 3B–E). remarkable differences regarding function account discrepancy Patients featured cellular proliferation status, line Low predominantly distinguished infiltration, indicated harbored more reserves immunization resources immunotherapy. conclusion, investigated HCC-infiltrating (termed HIRIPS) from algorithms. This displayed stable might serve latent biomarker immunotherapy response. our study provided promising platform optimizing precise treatment authors declare they no competing interests. Please note: publisher not responsible content or functionality any supporting supplied authors. Any queries (other than missing content) should be directed corresponding author article.

Language: Английский

Young Exosome Bio‐Nanoparticles Restore Aging‐Impaired Tendon Stem/Progenitor Cell Function and Reparative Capacity DOI
Shanshan Jin, Yu Wang,

Xiaolan Wu

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(18)

Published: Feb. 13, 2023

Aging impairs tendon stem/progenitor cell function and homeostasis, however, effective treatments for aging-induced diseases are lacking. Exosomes naturally derived nanoparticles that contain bioactive molecules, therefore, have attracted great interest in tissue engineering regenerative medicine. In this study, it is shown young exosomes secreted by stem cells from human exfoliated deciduous teeth (SHED-Exos) possess abundant anti-aging signals. These bio-nanoparticles can alleviate the aging phenotypes of aged (AT-SCs) maintain their tenogenic capacity. Mechanistically, SHED-Exos modulate histone methylation inhibit nuclear factor-κB to reverse AT-SC aging. a mouse model, systemic administration SHED-Exo retards degeneration. Interestingly, local delivery SHED-Exos-loaded microspheres confers phenotypes, including reduced senescent decreased ectopic bone formation, thereby functionally structurally rescuing endogenous regeneration repair capacity rats. Overall, SHED-Exos, as natural nanoparticles, promising translational therapeutic potential aging-related diseases.

Language: Английский

Citations

71
PLAGL2 promotes bladder cancer progression via RACGAP1/RhoA GTPase/YAP1 signaling DOI Creative Commons
Hualin Chen, Wenjie Yang, Yingjie Li

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(7)

Published: July 15, 2023

Abstract PLAGL2 is upregulated in various tumors, including bladder cancer (BCa). However, the mechanisms underlying tumorigenic effects of BCa remain unclear. In our study, we proved that was overexpressed tissues and correlated with decreased survival. Functionally, deficiency significantly suppressed proliferation metastasis cells vitro vivo. RNA sequencing, qRT‒PCR, immunoblotting, immunofluorescence staining, luciferase reporter, ChIP assays revealed disrupted Hippo pathway increased YAP1/TAZ activity by transactivating RACGAP1. Further investigations demonstrated activated signaling via RACGAP1-mediated RhoA activation. Importantly, inhibitor simvastatin or verteporfin abrogated proproliferative prometastatic enhanced PLAGL2. These findings suggest promotes progression RACGAP1/RhoA GTPase/YAP1 signaling. Hence, core nodes may be promising therapeutic targets for BCa.

Language: Английский

Citations

19
Analyzing the impact of metabolism on immune cells in tumor microenvironment to promote the development of immunotherapy DOI Creative Commons

Yanru Long,

Houhui Shi,

Yuedong He

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

Tumor metabolism and tumor immunity are inextricably linked. Targeting the of tumors is a point worth studying in immunotherapy. Recently, influence immune cells on occurrence, proliferation, metastasis, prognosis has attracted more attention. tissue forms specific microenvironment (TME). In addition to cells, there also stromal other TME. To adapt environment, go through reprogramming various substances. The may further affect formation function variety especially eventually promoting development. Therefore, it necessary study its effects guide Inhibiting restore balance promote response tumors. This article will describe glucose metabolism, lipid amino acid Besides, impact TME discussed for analyzing exploring

Language: Английский

Citations

6
Advances in research on immune escape mechanism of glioma DOI Creative Commons
Xu Guo, Gang Wang

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 29(7), P. 1709 - 1720

Published: April 23, 2023

Abstract Background Glioma is the most common primary intracranial malignancy in clinical practice, and particular, IDH‐wildtype glioblastoma has worst prognosis. In recent years, surgical resection combined with simultaneous radiotherapy immune checkpoint inhibitors made some progress, but efficacy still not satisfactory, which may be related to low immunogenicity of glioma cells tumor immunosuppressive microenvironment. Methods A comprehensive review relevant literature was conducted explore mechanisms by tumors suppress antitumor responses produce escape, a focus on microenvironment (TME). Results The involved evasion are complex involve cell differentiation function. Conclusion Our emphasizes need for more profound comprehension response glioma, formulate efficacious treatment modalities.

Language: Английский

Citations

11
Harnessing Pseudogenes for Lung Cancer: A Novel Epigenetic Target in Diagnosis, Prognosis and Treatment DOI
Yock Young Dan, Xinyi Zhao, Jing Li

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2025, Volume and Issue: 208, P. 104645 - 104645

Published: Feb. 1, 2025

Language: Английский

Citations

0
Exosomes: a double‐edged sword in cancer immunotherapy DOI Creative Commons
Jiayi Chen,

Siyuan Hu,

Jiayi Liu

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: Feb. 17, 2025

Abstract Over the past few decades, immunotherapy has emerged as a powerful strategy to overcome limitations of conventional cancer treatments. The use extracellular vesicles, particularly exosomes, which carry cargoes capable modulating immune response, been extensively explored potential therapeutic approach in immunotherapy. Exosomes can deliver their cargo target cells, thereby influencing phenotype and immunomodulatory functions. They exhibit either immunosuppressive or immune‐activating characteristics, depending on internal contents. These exosomes originate from diverse cell sources, contents vary, suggesting that there may be delicate balance between suppression stimulation when utilizing them for Therefore, thorough understanding molecular mechanisms underlying role progression is essential. This review focuses driving exosome function impact tumor microenvironment (TME), highlighting intricate activation must navigated exosome‐based therapies. Additionally, it underscores challenges ongoing efforts optimize immunotherapies, making significant contribution advancement research.

Language: Английский

Citations

0
Focused ultrasound combined with miR-1208-equipped exosomes inhibits malignant progression of glioma DOI

Ying Zhan,

Yichen Song, Wei Qiao

et al.

British Journal of Cancer, Journal Year: 2023, Volume and Issue: 129(7), P. 1083 - 1094

Published: Aug. 14, 2023

Language: Английский

Citations

10
The multifaceted roles of small extracellular vesicles in metabolic reprogramming in the tumor microenvironments DOI
Zhixian Chen, Judy Wai Ping Yam, Xiaowen Mao

et al.

PROTEOMICS, Journal Year: 2024, Volume and Issue: 24(11)

Published: Jan. 3, 2024

Abstract The link between metabolism and tumor progression has been extensively researched for a long time. With the increasing number of studies uncovering multiple functions metabolic reprogramming in microenvironments, regulatory network seems to become even more intricate at same Small extracellular vesicles (sEV), as crucial mediators facilitating intercellular communications, exhibit significant involvement regulating within complicated microenvironments. sEV derived from cells those released by other cell populations such tumor‐associated macrophages (TAMs) cancer‐associated fibroblasts (CAFs) can mutually influence each other, giving rise diverse complex feedback loops. This review includes conducted recent years summarize altering various types Additionally, it aims highlight potential therapeutic targets based on commonly observed mechanisms identified different studies.

Language: Английский

Citations

3
Cancer-associated fibroblast-associated gene IGFBP2 promotes glioma progression through induction of M2 macrophage polarization DOI
Xiaobin Zhang, Xiaolin Sun, Guo Chen

et al.

AJP Cell Physiology, Journal Year: 2023, Volume and Issue: 326(1), P. C252 - C268

Published: Nov. 20, 2023

We elucidated the molecular mechanism of cancer-associated fibroblast (CAF)-associated gene insulin-like growth factor binding protein-2 (IGFBP2)-induced M2 macrophage polarization in tumor microenvironment involved glioma progression. The Cancer Genome Atlas (TCGA) and Chinese Glioma (CGGA) provided bulk RNA-sequencing datasets, ESTIMATE scores for stromal cells, overall survival-clinicopathological correlation analyses. TIMER CAF abundance TCGA glioma-related dataset, differential analysis was performed high- low-CAF groups, weighted coexpression network identified CAF-related genes. Univariate multifactorial cyclooxygenase (COX) regression analyses created risk models single sample set enrichment analysis, CIBERSORT, GSE84465. Mice were implanted with gliomas, Western blot RT-quantitative PCR showed IGFBP2 tissues. Adeno-associated virus (AAV) decreased IGFBP2, flow cytometry measured M1 ratios, immunohistochemistry detected markers. CGGA transcriptome data malignant gliomas had higher cell worse prognoses. Low- high-CAF detected, expression, WGCNA, COX 132 genes seven high-risk (CPQ, EFEMP2, RAB42, TNFRSF12A, VASN). Neither score, grade, nor 1p/19q affected prognosis. only enriched EFEMP2 IGFBP2. Gene Expression Profiling Interactive Analysis compared expression normal brain tissue gliomas. Low-grade glioblastoma highly expressed EFEMP2. GSEA raised CIBERSORT linked infiltration to immune subpopulation expression. knockdown stopped mouse polarization. plays a procarcinogenic role glioma, could promote progression by inducing

Language: Английский

Citations

8
From bench to bedside: The promising value of exosomes in precision medicine for CNS tumors DOI Creative Commons
Mengjie Wang,

Jin Feng,

Xiaoguang Tong

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(11), P. e32376 - e32376

Published: June 1, 2024

Exosomes are naturally present extracellular vesicles (EVs) released into the surrounding body fluids upon fusion of polycystic and plasma membranes. They facilitate intercellular communication by transporting DNA, mRNA, microRNA, long non-coding RNA, circular proteins, lipids, nucleic acids. contribute to onset progression Central Nervous System (CNS) tumors. In addition, they can be used as biomarkers tumor proliferation, migration, blood vessel formation, thereby affecting Tumor Microenvironment (TME). This paper reviews recent advancements in diagnosis treatment exosomes various CNS tumors, promise challenges natural carriers therapeutic prospects Furthermore, we hope this research development more targeted effective treatments for central nervous system

Language: Английский

Citations

1