EZH2: a novel target for cancer treatment

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: July 28, 2020

Abstract Enhancer of zeste homolog 2 (EZH2) is enzymatic catalytic subunit polycomb repressive complex (PRC2) that can alter downstream target genes expression by trimethylation Lys-27 in histone 3 (H3K27me3). EZH2 could also regulate gene ways besides H3K27me3. Functions cells proliferation, apoptosis, and senescence have been identified. Its important roles the pathophysiology cancer are now widely concerned. Therefore, targeting for therapy a hot research topic different types inhibitors developed. In this review, we summarize structure action modes EZH2, focusing on up-to-date findings regarding role initiation, progression, metastasis, metabolism, drug resistance, immunity regulation. Furtherly, highlight advance therapies experiments clinical studies.

Language: Английский

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LINC00861 inhibits the progression of cervical cancer cells by functioning as a ceRNA for miR‑513b‑5p and regulating the PTEN/AKT/mTOR signaling pathway

Molecular Medicine Reports, Journal Year: 2020, Volume and Issue: 23(1), P. 1 - 1

Published: Nov. 3, 2020

Long non‑coding RNAs (lncRNAs) have been discovered to serve important roles in a variety of types cancer, including cervical cancer. The low expression lncRNA long intergenic non‑protein coding RNA 861 (LINC00861) is related poor prognosis ovarian However, the effects and underlying mechanisms LINC00861 cancer remain largely unknown. present study aimed examine role development progression its mechanisms. levels microRNA (miR)‑513b‑5p were analyzed using reverse transcription‑quantitative PCR analysis. Cell proliferation, migration invasion measured by Counting Kit‑8, colony formation, wound healing Transwell assays, respectively. A luciferase assay was used determine whether miR‑513b‑5p targeted PTEN. protein western blot assay. results that significantly downregulated tissues CaSki ME‑180 cell lines. Downregulated identified be associated with an advanced‑stage, lymph node metastasis survival patients Gene Set Enrichment Analysis revealed PI3K/AKT/mTOR signaling pathway enriched tumors expressing compared high LINC00861. overexpression reduced migration, epithelial‑mesenchymal transition (EMT) processes, upregulated PTEN phosphorylated (p)‑AKT p‑mTOR levels. regulatory relationship between LINC00861, validated dual reporter gene mimic group inhibitor NC both Furthermore, suggested as competing endogenous sponging consequently upregulating cells. PTEN, phosphorylation Akt mTOR EMT phenotype rescued following co‑transfection mimics. In conclusion, findings indicated LINC00861/miR‑513b‑5p axis may inhibit cells through PTEN/AKT/mTOR suppress process.

Language: Английский

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The Myc Family and the Metastasis Suppressor NDRG1: Targeting Key Molecular Interactions with Innovative Therapeutics

Pharmacological Reviews, Journal Year: 2023, Volume and Issue: 75(5), P. 1007 - 1035

Published: June 6, 2023

Cancer is a leading cause of death worldwide resulting in ~10 million deaths 2020. Major oncogenic effectors are the Myc proto-oncogene family that consists three members including c-Myc, N-Myc, and L-Myc. As pertinent example role tumorigenesis, amplification MYCN childhood neuroblastoma strongly correlates with poor patient prognosis. Complexes between oncoproteins their partners such as hypoxia-inducible factor-1α (HIF-1α) Myc-associated protein X (MAX) results proliferation arrest pro-proliferative effects, respectively. Interactions other proteins also important for N-Myc activity. For instance, enhancer zest homolog 2 (EZH2) binds directly to stabilize it by acting competitor against ubiquitin ligase, SCFFBXW7, which prevents proteasomal degradation. Heat shock 90 may be involved stabilization since EZH2 its downstream-regulated gene 1 (NDRG1) down-regulated participates regulation cellular via associating proteins, glycogen synthase kinase-3β (GSK3β) low-density lipoprotein receptor-related 6 (LRP6). These molecular interactions provide better understanding biological roles NDRG1, can potentially used therapeutic targets. In addition targeting these disrupting key promising strategy anti-cancer drug development. This review examines molecules, special focus on relationship NDRG1 possible interventions. Significance Statement Neuroblastoma (NB) one most common solid tumors, dismal 5-year survival rate. problem makes imperative discover new more effective therapeutics. The major drivers e.g., metastasis suppressor, targets anti-neuroblastoma discovery.

Language: Английский

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PSMA3-AS1 induced by transcription factor PAX5 promotes cholangiocarcinoma proliferation, migration and invasion by sponging miR-376a-3p to up-regulate LAMC1

Aging, Journal Year: 2022, Volume and Issue: 14(1), P. 509 - 525

Published: Jan. 12, 2022

Long noncoding RNAs (lncRNAs) have been reported to exhibit a crucial regulatory role in tumor progression, including cholangiocarcinoma (CCA). As promising lncRNA, proteasome 20S subunit alpha 3 antisense RNA 1 (PSMA3-AS1) is involved development of various tumors. However, the and function PSMA3-AS1 CCA remain unclear. The aim this study examine expression, function, mechanism, clinical significance development. By TCGA database analysis, we found that was overexpressed CCA. Consistent with significantly tissues cells by RT-qPCR. Upregulated related lymph node invasion, advanced TNM stage poor survival, an independent risk factor prognosis for patients. Functionally, CCK-8, EdU colony formation assays confirmed upregulated promoted cell proliferation, whereas downregulated inhibited proliferation. This result further subcutaneous nude mice. Wound healing transwell increased migration decreased these biological phenotypes. In addition, EMT process downregulating E-cadherin upregulating N-cadherin vimentin. Mechanistically, transcription PAX5 bound promoter region its transcription. Simultaneously, primarily localized cytoplasm could competitively bind miR-376a-3p upregulate LAMC1, thereby accelerating progression. uncovers functions as cancer-promoting gene CCA, PAX5/PSMA3-AS1/miR-376a-3p/LAMC1 axis plays vital

Language: Английский

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Enhancer zeste homolog 2 (EZH2) targeting by small interfering RNA (siRNA); recent advances and prospect

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Language: Английский

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PSMA3-AS1: a promising LncRNA as a diagnostic and prognostic biomarker in human cancers

Gene, Journal Year: 2025, Volume and Issue: unknown, P. 149521 - 149521

Published: April 1, 2025

Language: Английский

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Single-Cell Proteomics Uncovers Dual Traits of Dermal Sheath Cells in Wound Repair

Advances in Wound Care, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Wound healing is a dynamic process involving multiple cell types and signaling pathways. Dermal sheath cells (DSCs), residing surrounding hair follicles, play critical role in tissue repair, yet their regulatory mechanisms remain unclear. This study used single-cell proteomics with the AcanCreER;R26LSL-tdTomato-DTR mouse model to explore DSC function across different stages. All animal procedures were conducted accordance Animal Research: Reporting of In Vivo Experiments guidelines. Gene set enrichment analysis (GSEA) temporal clustering (Mfuzz) employed reveal functional shifts. GSEA identified enriched gene sets related interferon-gamma response, inflammatory ultraviolet myogenesis, xenobiotic metabolism. Temporal revealed eight distinct clusters: clusters associated early contracting proliferative phases linked metabolic activation oxidative stress, while from later remodeling phase emphasized extracellular matrix structural reorganization. The expression epithelial-mesenchymal transition-related genes keratins supported DSCs' dual epithelial mesenchymal traits. Additionally, keratins, collagens, integrins, actin proteins emerged as promising markers or signature molecules for DSCs. reveals traits during wound providing basis therapies enhance healing.

Language: Английский

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Long noncoding RNA PSMA3-AS1 functions as a competing endogenous RNA to promote gastric cancer progression by regulating the miR-329-3p/ALDOA axis

Biology Direct, Journal Year: 2023, Volume and Issue: 18(1)

Published: July 4, 2023

Abstract LncRNA PSMA3-AS1 functions as an oncogene in several cancers, including ovarian cancer, lung and colorectal cancer. However, its role gastric cancer (GC) progression remains unclear. In this study, the levels of PSMA3-AS1, miR-329-3p, aldolase A (ALDOA) 20 paired human GC tissues adjacent nontumorous were measured by real-time PCR. cells transfected with recombinant plasmid carrying full-length or shRNA targeting PSMA3-AS1. The stable transfectants selected G418. Then, effects knockdown overexpression on vitro vivo evaluated. results showed that was highly expressed tissues. Stable significantly restrained proliferation/migration/invasion, enhanced cell apoptosis, induced oxidative stress vitro. Tumor growth matrix metalloproteinase expression tumor markedly inhibited, while nude mice after knockdown. Additionally, negatively regulated miR-329-3p positively ALDOA expression. MiR-329-3p directly targeted ALDOA-3′UTR. Interestingly, partially attenuated tumor-suppressive Conversely, exhibited opposite effects. promoted regulating miR-329-3p/ALDOA axis. might serve a promising effective target for treatment.

Language: Английский

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MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma

World Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 30(11), P. 1497 - 1523

Published: March 21, 2024

Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor, characterized by differentiation, it the sixth leading cause of cancer-related deaths globally. The increased mortality rate ESCC patients predominantly due to advanced stage disease when discovered, coupled with higher risk metastasis, which an exceedingly characteristic cancer, frequently high rate. Unfortunately, there currently no specific and effective marker predict treat metastasis in ESCC. MicroRNAs (miRNAs) are class small non-coding RNA molecules, approximately 22 nucleotides length. miRNAs vital modulating gene expression serve pivotal regulatory roles occurrence, progression, prognosis cancer. Here, we have examined literature highlight intimate correlations between show that regulated or genetic epigenetic factors. This review proposes potential role for as diagnostic therapeutic biomarkers ultimate aim reducing among

Language: Английский

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Long non-coding RNA PSMA3-AS1 promotes glioma progression through modulating the miR-411-3p/HOXA10 pathway

BMC Cancer, Journal Year: 2021, Volume and Issue: 21(1)

Published: July 22, 2021

Glioma is a common type of brain tumor and classified as low high grades according to morphology molecules. Growing evidence has proved that long non-coding RNAs (lncRNAs) play pivotal roles in numerous tumors or diseases including glioma. Proteasome 20S subunit alpha 3 antisense RNA 1 (PSMA3-AS1), member lncRNAs, been disclosed tumor-promoting role cancer progression. However, the PSMA3-AS1 glioma remains unknown. Therefore, we concentrated on researching regulatory mechanism glioma.PSMA3-AS1 expression was detected using RT-qPCR. Functional assays were performed measure effects After that, ENCORI ( http://starbase.sysu.edu.cn/ ) database used predict potential genes could bind PSMA3-AS1, miR-411-3p chosen for further studies. The interaction among homeobox A10 (HOXA10) confirmed through assays.PSMA3-AS1 verified be up-regulated cells promote Furthermore, act competitive endogenous (ceRNA) regulate HOXA10 thus affecting progression.PSMA3-AS1 stimulated progression via miR-411-3p/HOXA10 pathway, which might offer novel insight therapy treatment

Language: Английский

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