FARSB Facilitates Hepatocellular Carcinoma Progression by Activating the mTORC1 Signaling Pathway

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(23), P. 16709 - 16709

Published: Nov. 24, 2023

Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality. Human phenylalanine tRNA synthetase (PheRS) comprises two α catalytic subunits encoded by the FARSA gene and β regulatory FARSB gene. potential oncogene, but no experimental data show relationship between HCC progression. We found that expression of in liver cancer closely related to patients' low survival poor prognosis. In cells, mRNA protein levels are increased promote cell proliferation migration. Mechanistically, activates mTOR complex 1 (mTORC1) signaling pathway binding component Raptor mTORC1 play role promoting cancer. addition, we can inhibit erastin-induced ferroptosis regulating pathway, which may be another mechanism promotes summary, progression associated prognosis patients. expected biomarker for early screening treatment HCC.

Language: Английский

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Non-coding RNAs in Hepatocellular Carcinoma: Potential Applications in Combined Therapeutic Strategies and Promising Candidates of Treatment Response

Published: Jan. 22, 2024

The incidence of hepatocellular carcinoma (HCC) is increasing and 40% patients are diagnosed at advanced stages. Over the past 5 years, number clinical available treatments have dramatically increased for HCC, making patient management particularly complex. Immune checkpoint inhibitors (ICIs) improved overall survival showing a durable treatment benefit over time, different response pattern with respect to tyrosine kinase (TKIs). Although in responder cases, sizeable group primary progressors or ineligible immunotherapy. Indeed, non-viral etiologies, such non-alcoholic steatohepatitis (NASH), alterations specific driver genes might be less responsive Therefore, improving comprehension mechanisms drug resistance identifying biomarkers informative best approach required actions improve survival. Numerous evidence indicated non-coding RNAs (ncRNAs) as pivotal players cancer. Molecular through which ncRNAs exert their effects cancer progression been widely investigated. Nevertheless, there no studies summarizing synergistic effect between ncRNA-based strategies TKIs ICIs preclinical setting. This review aims provide up-to-date information regarding possible use therapeutic targets association molecular targeted agents immunotherapies predictive tools selection optimized options HCCs.

Language: Английский

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A Novel Cholesterol Metabolism-Related lncRNA Signature Predicts the Prognosis of Patients with Hepatocellular Carcinoma and Their Response to Immunotherapy

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(3)

Published: March 22, 2024

Background: The survival rate of hepatocellular carcinoma (HCC) is low and the prognosis poor. Metabolic reprogramming still an emerging hallmark cancer, cholesterol metabolism plays a crucial action in tumor pathogenesis. Increasing evidence suggests that affects cell proliferation, invasion, migration, resistance to chemotherapy HCC. To date, no long noncoding RNA (lncRNA) signature associated with has been developed predict outcome patients Methods: RNA-seq data as well prognostic clinical were obtained from Cancer Genome Atlas (TCGA) database. We conducted univariate multivariate analyses assess metabolism-related lncRNAs correlated HCC order construct signature. Functional differences between low- high-risk groups investigated using genomic enrichment analysis (GSEA). Kaplan-Meier (KM) curves applied explore overall (OS) groups. Single-sample (ssGSEA) was investigate association this predictive immune function. subsequently examined how relates treatment response patients. Results: A comprising six related constructed (AC124798.1, AL031985.3, AC103760.1, NRAV, WAC-AS1 AC022613.1). found low-risk showed better than In patients, lncRNA may be served independent factor. Cholesterol had higher diagnostic efficiency compared clinicopathologic variables. After stratifying according different clinicopathological variables, longer OS ssGSEA demonstrated closely status GSEA immune- tumor-related pathways predominantly enriched group. High-risk more responsive checkpoint inhibitors (ICIs) conventional chemotherapeutic agents. Conclusions: This can guide management including immunotherapy.

Language: Английский

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LINC01134: a pivotal oncogene with promising predictive maker and therapeutic target in hepatocellular carcinoma

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

Published: Feb. 21, 2024

Hepatocellular carcinoma (HCC) represents a leading and fatal malignancy within the gastrointestinal tract. Recent advancements highlight pivotal role of long non-coding RNAs (lncRNAs) in diverse biological pathways pathologies, particularly tumorigenesis. LINC01134, particular lncRNA, has attracted considerable attention due to its oncogenic potential hepatoma. Current research underscores LINC01134’s augmenting onset progression HCC, with notable implications drug resistance. This review comprehensively explores molecular functions regulatory mechanisms LINC01134 offering fresh perspective for therapeutic interventions. By delving into multifaceted roles, we aim foster novel strategies HCC management.

Language: Английский

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The Risk Signature of Pyroptosis-Related Long Noncoding RNAs Predicts Prognosis and Indicates Immunotherapeutic Efficiency in Hepatocellular carcinoma

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 14, 2024

Abstract Pyroptosis can cause inflammasome activation through Caspase-1/NOD-like receptor 3 (NLRP3) pathways, which is closely related to hepatocellular carcinoma (HCC). The immunotherapy of HCC has a good overall effect and been widely used in clinical, but the exact varies from person person. Dysregulation lncRNA lead inflammatory abnormal immune microenvironment HCC. However, few studies have reported role for pyroptosis-related lncRNAs (PRlncRNAs) In this study, we constructed validated risk model based on 8 PRlncRNAs predict prognosis patients cell infiltration using bioinformatics approaches experiments. Our showed that high-risk group exhibited poor score an independent prognostic factor. AUC analysis proved our signature more accurately predicted than traditional clinicopathological indexes. results GSEA (ss)GSEA genes were mainly enriched pathways their executive function depended inhibitory checkpoints. Furthermore, downregulation AC009283.1 expression accelerated cells progression, reduced NLRP3/Caspase-1 CD3. While si-LINC00942 got opposite results. Overall, novel high credibility predicting patient evaluating status, important significance guiding developing precise treatments benefit patients.

Language: Английский

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Reprogramming tumor-associated macrophages and inhibiting tumor neovascularization by targeting MANF-HSF1-HSP70-1 pathway: An effective treatment for hepatocellular carcinoma

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(10), P. 4396 - 4412

Published: May 10, 2024

In advanced hepatocellular carcinoma (HCC) tissues, M2-like tumor-associated macrophages (TAMs) are in the majority and promotes HCC progression. Contrary to pro-tumor effect of TAMs, M1-like TAMs account for a small proportion have anti-tumor effects. Since can switch from one type another, reprogramming may be an important treatment therapy. However, mechanisms phenotypic still obscure. this study, we analyzed differential genes normal found that loss MANF accompanied by high levels downstream negatively regulated MANF. reprogrammed into M1 phenotype. Meanwhile, promoted progression patients mice model, especially tumor neovascularization. Additionally, with supplement suppressed mice, suggesting macrophage was effective HCC. Mechanistically, enhanced HSF1-HSP70-1 interaction, restricted HSF1 cytoplasm macrophages, decreased both mRNA protein HSP70-1, which turn led suppressing neovascularization Our study contributes exploration mechanism reprogramming, provide insights future therapeutic exploitation

Language: Английский

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Pyroptosis in Lung Cancer: The Emerging Role of Non-Coding RNAs

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 263, P. 155619 - 155619

Published: Sept. 28, 2024

Language: Английский

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Therapeutic Potential of lncRNAs in Regulating Disulfidptosis for Cancer Treatment

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 263, P. 155657 - 155657

Published: Oct. 16, 2024

Language: Английский

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Analysis of competing risks of cardiovascular death in patients with hepatocellular carcinoma: A population-based study

Medicine, Journal Year: 2023, Volume and Issue: 102(51), P. e36705 - e36705

Published: Dec. 22, 2023

Clinical data has shown that cardiovascular diseases (CVDs) have emerged as a prominent cause of mortality in individuals with hepatocellular carcinoma (HCC). This research aimed to reveal the comorbid effects CVDs patients HCC. The diagnosed HCC between 2000 and 2014 was compared general US population. Standardized ratios were calculated quantify relative risk patients. cumulative incidence death (CVD) estimated using Fine-Gray testing, independent factors for CVD determined competing models. results analyzed Kaplan-Meier analysis. overall SMR 11.15 (95% CI: 10.99-11.32). significantly higher aged < 55 years (SMR: 56.19 [95% 54.97-57.44]) those ≥ 75 1.86 1.75-1.97]). study suggests are at significant developing CVD. Competing analyses indicated age, grade, tumor size, surveillance, epidemiology, end stage, surgical status Therefore, require enhanced preventive screening management during after treatment improve patient survival.

Language: Английский

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Liver Regeneration-Related Genes of Nontumor Liver Tissues Predict the Prognosis of Patients with Hepatocellular Carcinoma

Journal of Hepatocellular Carcinoma, Journal Year: 2023, Volume and Issue: Volume 10, P. 2197 - 2209

Published: Dec. 1, 2023

Hepatocellular carcinoma (HCC) is one of the most serious malignant tumors threatening human life with a high mortality rate. The liver regenerative capacity after hepatectomy in early-stage HCC patients influenced by various factors, including surgical methods and energy metabolism. This study aims to provide prognostic model based on genes related regeneration that can predict prognosis non-tumor tissues patients.A total 584 from were collected three independent databases. Kaplan-Meier survival curves used identify liver-regeneration genes. Subsequently, indicator, designated as Liver Regeneration score (LR score), was determined using single-sample gene set enrichment analysis (ssGSEA). Independent cohorts verify relationship between LR patients. Furthermore, regeneration-related established validate key identified through LASSO Cox regression analysis.We constructed comprising 24 genes, utilized its levels tissues. In patients, higher scores associated improved prognosis. Higher indicate metabolism revealed Enrichment analysis. two DHTKD1 (dehydrogenase E1 transketolase domain containing 1) PHYH (phytanoyl-CoA 2-hydroxylase), expression these correlated better also changed corresponding progression regeneration.In summary, our has introduced novel signature for providing predictive estimating clinical demonstrates promise reliable indicator predicting overall HCC.

Language: Английский

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