LncRNA-PVT1 was identified as a key regulator for TMZ resistance and STAT-related pathway in glioma DOI Creative Commons
Yusheng Chen,

Fengjin Ma,

Zhe Zhang

et al.

BMC Cancer, Journal Year: 2023, Volume and Issue: 23(1)

Published: May 18, 2023

Abstract Background PVT1, a previously uncharacterized lncRNA, was identified as critical regulator involved in multiple functions tumor, including cell proliferation, motility, angiogenesis and so on. However, the clinical significance underlying mechanism of PVT1 not be fully explored glioma. Methods In this study, 1210 glioma samples with transcriptome data from three independent databases (CGGA RNA-seq, TCGA RNA-seq GSE16011 cohorts) were enrolled study. Clinical information genomic profiles containing somatic mutations DNA copy numbers collected cohort. The R software performed for statistical calculations graphics. Furthermore, we validated function vitro. Results results indicated that higher expression associated aggressive progression Cases always accompanied by PTEN EGFR alteration. addition, functional analyses western blot suggested inhibited sensitivity TMZ chemotherapy via JAK/STAT signaling. Meanwhile, knockdown increased TZM Finally, high reduced survival time may serve strong prognostic indicator gliomas. Conclusions This study demonstrated strongly correlated tumor chemo-resistance. become potential biomarker diagnosis treatment

Language: Английский

MicroRNA Signature in Melanoma: Biomarkers and Therapeutic Targets DOI Creative Commons
Soudeh Ghafouri‐Fard, Mahdi Gholipour, Mohammad Taheri

et al.

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: April 22, 2021

Melanoma is the utmost fatal kind of skin neoplasms. Molecular changes occurring during pathogenic processes initiation and progression melanoma are diverse include activating mutations in BRAF NRAS genes, hyper-activation PI3K/AKT pathway, inactivation p53 alterations CDK4/CDKN2A axis. Moreover, several miRNAs have been identified to be implicated biology through modulation expression genes being involved these pathways. In current review, we provide a summary bulk information about role pathobiology melanoma, their possible application as biomarkers emerging therapeutic targets for this cancer.

Language: Английский

Citations

42
Identification of m7G-associated lncRNA prognostic signature for predicting the immune status in cutaneous melanoma DOI Creative Commons

Jie-lin Rong,

Hui Wang, Yi Yao

et al.

Aging, Journal Year: 2022, Volume and Issue: 14(12), P. 5233 - 5249

Published: June 29, 2022

RNA modifications, including methylation, are widely existed in cutaneous melanoma (CM). Among epigenetic N7-methylguanosine (m7G) is a kind of modification at 5’ cap which participate maintaining the stability mRNA and various cell biological processes. However, there still no study concerning relationship between CM m7G methylation complexes, METTL1 WDR4. Here, long non-coding (lncRNAs) gene expression data from Cancer Genome Atlas (TCGA) database were retrieved to identify differentially expressed m7G-related lncRNAs connected with overall survival CM. Then, Cox regression analyses was applied construct lncRNA risk signature, prognostic value identified signature further evaluated. As result, 6 m7G-associated that significantly related prognosis incorporated into our signature. The functional indicated model correlated patient survival, cancer metastasis, growth. Meanwhile, its diagnostic accuracy better than conventional clinicopathological characteristics. pathway enrichment analysis showed enriched several immunity-associated pathways. Moreover, immune subtypes, infiltration cells, microenvironment, as well m6A-related genes tumor stem cells. Finally, nomogram based on calculated score established. Overall, generated presented predictive for patients can be used development novel therapeutic strategies

Language: Английский

Citations

37
Advances in Melanoma: From Genetic Insights to Therapeutic Innovations DOI Creative Commons
Fernando Valdez-Salazar,

Luis Alberto Jiménez-Del Río,

Jorge Ramón Padilla‐Gutiérrez

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(8), P. 1851 - 1851

Published: Aug. 14, 2024

Advances in melanoma research have unveiled critical insights into its genetic and molecular landscape, leading to significant therapeutic innovations. This review explores the intricate interplay between alterations, such as mutations BRAF, NRAS, KIT, pathogenesis. The MAPK PI3K/Akt/mTOR signaling pathways are highlighted for their roles tumor growth resistance mechanisms. Additionally, this delves impact of epigenetic modifications, including DNA methylation histone changes, on progression. microenvironment, characterized by immune cells, stromal soluble factors, plays a pivotal role modulating behavior treatment responses. Emerging technologies like single-cell sequencing, CRISPR-Cas9, AI-driven diagnostics transforming research, offering precise personalized approaches treatment. Immunotherapy, particularly checkpoint inhibitors mRNA vaccines, has revolutionized therapy enhancing body’s response. Despite these advances, mechanisms remain challenge, underscoring need combined therapies ongoing achieve durable comprehensive overview aims highlight current state transformative impacts advancements clinical practice.

Language: Английский

Citations

8
PURPL represses autophagic cell death to promote cutaneous melanoma by modulating ULK1 phosphorylation DOI Creative Commons
Shuo Han, Xue Li, Ke Wang

et al.

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(11)

Published: Nov. 10, 2021

Abstract Uncontrolled overactivation of autophagy may lead to autophagic cell death, suppression which is a pro-survival strategy for tumors. However, mechanisms involving key regulators in modulating death remain poorly defined. Here, we report novel long noncoding RNA, p53 upregulated regulator levels (PURPL), functions as an oncogene promote proliferation, colony formation, migration, invasiveness, and inhibits melanoma cells. Mechanistic studies showed that PURPL promoted mTOR-mediated ULK1 phosphorylation at Ser757 by physical interacting with mTOR constrain response avoid death. Loss led AMPK-mediated Ser555 Ser317 over-activate induce Our results identify modulate the activity initiation factor repress represent potential intervention target therapy.

Language: Английский

Citations

33
Targeting the epigenome in malignant melanoma: Facts, challenges and therapeutic promises DOI
Ioannis Anestopoulos, Sotiris Kyriakou, Venetia Tragkola

et al.

Pharmacology & Therapeutics, Journal Year: 2022, Volume and Issue: 240, P. 108301 - 108301

Published: Oct. 23, 2022

Language: Английский

Citations

21
PURPL Represses Radiation‐Induced Apoptosis to Promote Radioresistance in Cutaneous Melanoma by Direct Interfering With BID Cleavage DOI
Xue Li, Shuo Han, Xiaoting Liang

et al.

Pigment Cell & Melanoma Research, Journal Year: 2025, Volume and Issue: 38(3)

Published: April 14, 2025

ABSTRACT The rise of radioresistance in treating cutaneous melanoma challenges the efficacy radiotherapy. Transcriptomic sequencing highlights PURPL as one top upregulated long noncoding RNAs response to ionizing radiation (IR) treatment cells, suggesting its role radioresistance. To explore such hypothesis, loss‐of‐function experiments were conducted assess impact on cell viability, colony formation, and migration. Mechanistic studies using RNA pulldown identified BID interacting protein partner PURPL. Further analysis explored relationship among PURPL, BID, Caspase‐8 context IR‐induced DNA damage apoptosis through loss‐of‐ gain‐of‐function experiments. findings demonstrated that silencing significantly repressed migration, invasiveness, indicating potential promoting Moreover, was shown repress apoptosis, supporting involvement Mechanistically, inhibited interaction between Caspase‐8, thereby modulating mitochondrial pathway In conclusion, this study provides evidence pro‐radioresistance melanoma. vivo assays further corroborated vitro findings, highlighting clinical relevance targeting radioresistant By interfering with association may serve a novel therapeutic target for radiotherapy during

Language: Английский

Citations

0
Endogenous tRNA‐derived small RNA (tRF3‐Thr‐AGT) inhibits ZBP1/NLRP3 pathway‐mediated cell pyroptosis to attenuate acute pancreatitis (AP) DOI

Boshi Sun,

Zhuomiaoyu Chen, Qiang Chi

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2021, Volume and Issue: 25(22), P. 10441 - 10453

Published: Oct. 13, 2021

Abstract Endogenous transfer RNA‐derived small RNAs (tsRNAs) are newly identified that closely associated with the pathogenesis of multiple diseases, but involvement tsRNAs in regulating acute pancreatitis (AP) development has not been reported. In this study, we screened out a novel tsRNA, tRF3‐Thr‐AGT, was aberrantly downregulated acinar cell line AR42J treated sodium taurocholate (STC) and pancreatic tissues STC‐induced AP rat models. addition, STC treatment suppressed viability, induced pyroptotic death cellular inflammation models vitro vivo. Overexpression tRF3‐Thr‐AGT partially reversed detrimental effects on cells. Next, Z‐DNA‐binding protein 1 (ZBP1) as downstream target tRF3‐Thr‐AGT. Interestingly, upregulation NOD‐like receptor 3 (NLRP3)‐mediated STC‐treated cells via degrading ZBP1. Moreover, overexpression viability were abrogated by upregulating ZBP1 NLRP3. Collectively, our data indicated expressions to restrain NLRP3‐mediated This for first time, role potential underlying mechanisms which regulated pathogenesis.

Language: Английский

Citations

26
Development and Validation of a Novel Ferroptosis-Related LncRNA Signature for Predicting Prognosis and the Immune Landscape Features in Uveal Melanoma DOI Creative Commons
Xiaochen Ma,

Sejie Yu,

Bin Zhao

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: June 14, 2022

Ferroptosis is a newly iron-dependent mode of programmed cell death that involved in variety malignancies. But no research has shown link between ferroptosis-related long non-coding RNAs (FRLs) and uveal melanoma (UM). We aimed to develop predictive model for UM explore its potential function relation immune infiltration.Identification FRLs was performed using the Cancer Genome Atlas (TCGA) FerrDb databases. To prognostic signature, univariate Cox regression least absolute shrinkage selection operator (LASSO) were used training cohort. Kaplan-Meier (K-M) receiver operating characteristic (ROC) curve analyses assess reliability risk model. The immunological functions signature determined gene set enrichment analysis (GSEA). Immunological infiltration treatment studied ESTIMATE, CIBERSORT, ssGSEA algorithms. Finally, vitro assays carried out confirm biological roles with known primer sequences (LINC00963, PPP1R14B.AS1, ZNF667.AS1).A five-genes novel identified. mean score generated by this create two groups. high-risk patients had lower overall survival rate. area under (AUC) ROC K-M further validated strong prediction capacity signature. Immune cells such as memory CD8 T cells, M1 macrophages, monocytes, B showed substantial difference GSEA results linked certain pathways. Moreover, scores highly susceptible several chemotherapy drugs, cisplatin, imatinib, bortezomib, pazopanib. experimental validation confirmed knockdown three identified lncRNA ZNF667.AS1) suppressed invasive ability tumor vitro.The five-FRLs (AC104129.1, AC136475.3, LINC00963, effects on clinical immunotherapies patients.

Language: Английский

Citations

18
Deconstructing the role of MALAT1 in MAPK-signaling in melanoma: insights from antisense oligonucleotide treatment DOI Open Access
Valentin Feichtenschlager, Yixuan James Zheng,

Wilson Ho

et al.

Oncotarget, Journal Year: 2023, Volume and Issue: 14(1), P. 543 - 560

Published: May 26, 2023

The long non-coding RNA (lncRNA) MALAT1 is a regulator of oncogenesis and cancer progression. MAPK-pathway upregulation the main event in development progression human cancer, including melanoma recent studies have shown that has significant impact on regulation gene protein expression MAPK pathway. However, role kinases RAS, RAF, MEK ERK largely unknown. We demonstrate impacts antisense oligonucleotide (ASO)-based MALAT1-inhibition melanoma. Our results showed MALAT1-ASO treatment decreased BRAF levels, had increased correlation with associated genes patient samples compared to healthy skin. Additionally, drug-induced inhibition upregulated MALAT1-expression, finding resonates paradigm MALAT1-expression presented this work: downregulated other types which seems be MAPK-signaling, while strongly reduced growth cell lines, even cases resistance inhibition. significantly inhibited colony formation vitro tumor an NRAS-mutant xenograft mouse model vivo, showing no aberrant toxic side effects. findings new insights into MALAT1-mediated MAPK-signaling-dependent types. maintains essential oncogenic functions, despite being downregulated.

Language: Английский

Citations

10
LncRNAs and PTEN/PI3K signaling: A symphony of regulation in cancer biology DOI
Waleed Hassan Almalki

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 249, P. 154764 - 154764

Published: Aug. 15, 2023

Language: Английский

Citations

10