A novel autophagy‐related lncRNA prognostic risk model for breast cancer

Journal of Cellular and Molecular Medicine, Journal Year: 2020, Volume and Issue: 25(1), P. 4 - 14

Published: Nov. 20, 2020

Long non-coding RNAs (lncRNAs) are well known as crucial regulators to breast cancer development and implicated in controlling autophagy. LncRNAs also emerging valuable prognostic factors for patients. It is critical identify autophagy-related lncRNAs with value cancer. In this study, we identified by constructing a co-expression network of mRNAs-lncRNAs from The Cancer Genome Atlas (TCGA). We evaluated the these univariate multivariate Cox proportional hazards analyses eventually obtained risk model consisting 11 (U62317.4, LINC01016, LINC02166, C6orf99, LINC00992, BAIAP2-DT, AC245297.3, AC090912.1, Z68871.1, LINC00578 LINC01871). was further validated novel independent factor patients based on calculated score Kaplan-Meier analysis, regression time-dependent receiver operating characteristic (ROC) curve analysis. Moreover, model, low-risk high-risk groups displayed different autophagy oncogenic statues principal component analysis (PCA) Gene Set Enrichment Analysis (GSEA) functional annotation. Taken together, findings suggested that has significant might be therapeutic targets clinical practice.

Language: Английский

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Role of Hypoxia-Mediated Autophagy in Tumor Cell Death and Survival

Cancers, Journal Year: 2021, Volume and Issue: 13(3), P. 533 - 533

Published: Jan. 30, 2021

Programmed cell death or type I apoptosis has been extensively studied and its contribution to the pathogenesis of disease is well established. However, autophagy functions together with determine overall fate cell. The cross talk between this active self-destruction process quite complex contradictory as well, but it unquestionably decisive for survival death. Autophagy can promote tumor suppression also growth by inducing cancer-cell development proliferation. In review, we will discuss how reprograms cells in context hypoxic stress. We illustrate acts both a suppressor driver tumorigenesis through tuning dependent manner. shed light on relationship immune response regulation. A better understanding mechanisms pathways undoubtedly ameliorate design therapeutics aimed at targeting future cancer immunotherapies.

Language: Английский

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Tanshinone I improves TNBC chemosensitivity by suppressing late-phase autophagy through AKT/p38 MAPK signaling pathway

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 117037 - 117037

Published: July 3, 2024

The inhibition of autophagy is a potential therapeutic strategy to improve the chemosensitivity triple-negative breast cancer (TNBC). In this study, we demonstrated that natural terpenoid tanshinone I (TAN) enhanced effectiveness paclitaxel (PTX), at least in part, through an autophagy-dependent mechanism against TNBC. vitro validation combined therapy resulted synergistic decrease growth TNBC cells. chemosensitizing impact TAN might be attributed its PTX-induced late phase by obstructing fusion autophagosomes and lysosomes, rather than inhibiting lysosomal function. findings from KEGG pathway analysis molecular docking suggested chemoresistance primarily PI3K-Akt MAPK signaling pathways. non-canonical AKT/p38 was further validated as primary responsible for TAN. vivo study showed administration PTX more significant suppression tumor autophagic activity compared monotherapy MDA-MB-231 xenograft nude mouse model. safety evaluation zebrafish model, along with validation, provided experimental pre-clinical data supporting adjunctive Overall, suggests combination could provide effective treatment option advanced cancer, targeting MAPK/late-autophagy axis may promising approach developing interventions • Tanshinone exhibited increased sensitivity (TNBC) chemotherapy both settings. hindered degradation cells disrupting lysosomes. key suppressing late-phase displayed notable biocompatibility minor adverse effects validation.

Language: Английский

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Prognostic Value of SERPINA1 as a Biomarker for Poor Survival of Gliomas

Journal of Medical Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Abstract Background: Glioma is a primary brain tumor known for its aggressive behavior and poor prognosis. Alpha-1 antitrypsin (SERPINA1) protein with crucial role in regulating inflammatory processes the body. Prior research has shown that SERPINA1 enhances invasive metastatic capabilities of several cancer types, including lung, breast, colorectal cancer. Notably, also been found to be overexpressed human gliomas. Considering prognosis high mortality rate glioma, there an urgent demand more reliable biomarkers assess outcome. Aim: This study aims explore potential glioma by leveraging Gene Expression Profiling Interactive Analysis (GEPIA), Chinese Genome Atlas (CGGA), Omnibus (GEO) databases evaluate viability as prognostic biomarker glioma. Materials Methods: We analyzed GEPIA, CGGA, GEO mRNA expression link overall survival. The CGGA were utilized investigate interactions between proteins such proteinase 3, elastase neutrophil expressed (ELANE), PRSS3P2, KLK3, calnexin. Results: indicated significantly this overexpression strongly linked poorer In addition, analysis at single-cell level revealed elevated myeloid cells. Evaluation database further showed strong correlation ELANE Conclusion: Our findings suggest positively associated survival may serve valuable predicting outcomes patients.

Language: Английский

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Molecular characterization of breast cancer: a potential novel immune-related lncRNAs signature

Journal of Translational Medicine, Journal Year: 2020, Volume and Issue: 18(1)

Published: Nov. 7, 2020

Abstract Background Accumulating evidence has demonstrated that immune-related lncRNAs (IRLs) are commonly aberrantly expressed in breast cancer (BC). Thus, we aimed to establish an IRL-based tool improve prognosis prediction BC patients. Methods We obtained IRL expression profiles large cohorts (N = 911) from The Cancer Genome Atlas (TCGA) database. Then, light of the correlation between each and recurrence-free survival (RFS), screened prognostic signatures construct a novel RFS nomogram via Cox regression model. Subsequently, performance model was evaluated through discrimination, calibration ability, risk stratification ability decision curve analysis (DCA). Results A total 52 IRLs were TCGA. Based on multivariate analyses, four (A1BG-AS1, AC004477.3, AC004585.1 AC004854.2) two parameters (tumor subtype TNM stage) utilized as independent indicators develop In terms predictive accuracy, distinctly superior staging system (AUC: 0.728 VS 0.673, P 0.010). DCA indicated our had favorable clinical practicability. addition, showed efficiently divided patients into high- low-risk groups ( < 0.001). Conclusions constructed predict 5-year BC. Our can power identify high-risk with tumor recurrence implement more appropriate treatment strategies.

Language: Английский

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Proteomic analysis of breast cancer based on immune subtypes

Clinical Proteomics, Journal Year: 2024, Volume and Issue: 21(1)

Published: Feb. 29, 2024

Abstract Background Immunotherapy is applied to breast cancer resolve the limitations of survival gain in existing treatment modalities. With immunotherapy, a tumor can be classified into immune-inflamed, excluded and desert based on distribution immune cells. We assessed clinicopathological features, each subtype’s prognostic value differentially expressed proteins between subtypes. Methods Immune subtyping proteomic analysis were performed 56 cases with neoadjuvant chemotherapy. The was level tumor-infiltrating lymphocytes (TILs) Klintrup criteria. If TILs ≥ 10%, it as immune-inflamed type without consideration In 1–9% TIL, criteria 1–3 immune-excluded subtype not available (NA) NA. Cases 1% 0 immune-desert subtype. Mass spectrometry used identify formalin-fixed paraffin-embedded biopsy tissues. Results Of cases, 31 (55%) 21 (38%) immune-excluded, 2 (4%) Welch’s t-test revealed two immune-excluded/desert Coronin-1A upregulated tumors (adjusted p = 0.008) α-1-antitrypsin 0.008). Titin pathologic complete response (pCR) than non-pCR among 0.036). Conclusions subtypes, respectively. Titin's elevated expression pCR within may indicate favorable prognosis. Further studies involving large representative cohorts are necessary validate these findings.

Language: Английский

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In search of autophagy biomarkers in breast cancer: Receptor status and drug agnostic transcriptional changes during autophagy flux in cell lines

PLoS ONE, Journal Year: 2022, Volume and Issue: 17(1), P. e0262134 - e0262134

Published: Jan. 6, 2022

Autophagy drives drug resistance and drug-induced cancer cell cytotoxicity. Targeting the autophagy process could greatly improve chemotherapy outcomes. The discovery of specific inhibitors or activators has been hindered by challenges with reliably measuring levels in a clinical setting. We investigated breast lines differing ER/PR/Her2 receptor status exposing them to known but divergent inducers each unique molecular target, tamoxifen, trastuzumab, bortezomib rapamycin. Differential gene expression analysis from total RNA extracted during earliest sign flux showed both cell- drug-specific changes. analyzed list differentially expressed genes find common, drug-agnostic signature. Twelve mRNAs were significantly modulated all drugs 11 orthogonally verified Q-RT-PCR (Klhl24, Hbp1, Crebrf, Ypel2, Fbxo32, Gdf15, Cdc25a, Ddit4, Psat1, Cd22, Ypel3). agnostic mRNA signature was similarly induced mitochondrially targeted agent, MitoQ. In-silico on KM-plotter database that these are detectable human samples associated prognosis outcomes Relapse-Free Survival patients (RSF), Overall (OS), ER+ Patients (RSF ER+). High Klhl24, CD22 Ypel3 correlated better outcomes, whereas lower Ddit4 Psat1 patients. This uncovers candidate biomarkers be tested preclinical studies monitor process.

Language: Английский

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Pathogenic Single Nucleotide Polymorphisms on Autophagy-Related Genes

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(21), P. 8196 - 8196

Published: Nov. 2, 2020

In recent years, the study of single nucleotide polymorphisms (SNPs) has gained increasing importance in biomedical research, as they can either be at molecular origin a determined disorder or directly affect efficiency given treatment. this regard, sequence variations genes involved pro-survival cellular pathways are commonly associated with pathologies, alteration these routes compromises homeostasis. This is case autophagy, an evolutionarily conserved pathway that counteracts extracellular and intracellular stressors by mediating turnover cytosolic components through lysosomal degradation. Accordingly, autophagy dysregulation been extensively described wide range human including cancer, neurodegeneration, inflammatory alterations. Thus, it not surprising pathogenic gene variants encoding crucial effectors autophagosome/lysosome axis increasingly being identified. review, we present comprehensive list clinically relevant SNPs autophagy-related genes, highlighting scope relevance alterations disease.

Language: Английский

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A Prognostic Risk Signature of Two Autophagy-Related Genes for Predicting Triple-Negative Breast Cancer Outcomes

Breast Cancer Targets and Therapy, Journal Year: 2024, Volume and Issue: Volume 16, P. 529 - 544

Published: Sept. 1, 2024

Background: Triple-negative breast cancer (TNBC) is recognized as the most aggressive molecular subtype of cancer. Recent studies have highlighted complex role autophagy in pathogenesis TNBC. Methods: In this study, we evaluated 18,330 genes, including 1111 autophagy-related (ARGs), across 579 TNBC samples from online databases. Differentially expressed ARGs were identified using high-throughput RNA-seq data Cancer Genome Atlas (TCGA). Prognostic factors examined through Cox regression and multivariate analyses, with predictive efficacy assessed receiver operating characteristic (ROC) curves. A nomogram integrating risk signature clinicopathological factors, such TNM stage, was developed. Immunohistochemical analysis clinical also conducted. Results: EIF4EBP1 NPAS3 significantly correlated prognostic outcomes patients Multivariate demonstrated that expression levels these two genes accurate predictors disease progression TCGA GSE31519 dataset. The model validated ROC curve calibration plots, confirming its ability to accurately estimate 1-, 2-, 3-year survival rates for individuals Additionally, influenced drug sensitivity cell lines, notably lower tissues, particularly Stage III cases. This study first report Conclusion: may serve independent Keywords: autophagy, nomogram, prognosis, signature, triple-negative

Language: Английский

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Sanguisorba officinalis L. Suppresses Triple-Negative Breast Cancer Metastasis by Inhibiting Late-Phase Autophagy via Hif-1α/Caveolin-1 Signaling

Frontiers in Pharmacology, Journal Year: 2020, Volume and Issue: 11

Published: Dec. 14, 2020

Sanguisorba officinalis L. (SA) is a common herb for cancer treatment in the clinic, particularly during consolidation phase to prevent occurrence or metastasis. Nevertheless, there are limited studies reporting molecular mechanisms about its anti-metastatic function. It well demonstrated that autophagy one of critical accounting metastasis and anti-cancer pharmacological actions Chinese herbs. On threshold, regulatory effects SA suppressing autophagy-related breast were investigated this study. In vitro findings potently suppressed proliferation, colony formations as process triple-negative cancer. Network biological analyses predicted mainly targeted caveolin-1 (Cav-1) induce effects, core was via regulation autophagy. Further experiments-including western blotting, transmission electron microscopy, GFP-mRFP-LC3 immunofluorescence, lysosomal-activity detection-validated potent late-stage autophagic inhibitor by increasing microtubule-associated light chain 3-II (LC3-II) conversion, decreasing acidic vesicular-organelle formation, inducing lysosomal dysfunction even under conditions either starvation hypoxia. Furthermore, anti-autophagic activity Cav-1-dependent. Specifically, Cav-1 knockdown significantly facilitated SA-mediated inhibition hypoxia inducible factor-1α (Hif-1α) overexpression attenuated SA-induced inhibitory activities on Cav-1, autophagy, metastasis, indicating may have inhibited Hif-1α/Cav-1 signaling. both mouse xenograft zebrafish xenotransplantation models, growth late-phase vivo, which accompanied suppression signaling epithelial-mesenchymal transition. Overall, our not only indicate acts novel with cancer, but also highlight regulator controlling activity.

Language: Английский

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