Ubiquitin–proteasome system and the role of its inhibitors in cancer therapy DOI Creative Commons
Fatemeh Aziz‐Aliabadi, Beheshteh Sohrabi, Ebrahim Mostafavi

et al.

Open Biology, Journal Year: 2021, Volume and Issue: 11(4)

Published: April 1, 2021

Despite all the other cells that have potential to prevent cancer development and metastasis through tumour suppressor proteins, can upregulate ubiquitin–proteasome system (UPS) by which they degrade proteins avoid apoptosis. This plays an extensive role in cell regulation organized two steps. Each step has important controlling cancer. demonstrates importance of understanding UPS inhibitors improving these foster a new hope therapy. inhibitors, as less invasive chemotherapy drugs, are increasingly used alleviate symptoms various cancers malignant states. their success reducing with lowest side effects, thus far, appropriate inhibitor effectively inactivate this least drug resistance not yet been fully investigated. A fundamental is necessary elucidate its causing/controlling In review, we first comprehensively investigate system, then each containing ubiquitination protein degradation well discussed. Ultimately, advantages disadvantages some perspectives for efficiency

Language: Английский

Notch signaling pathway: architecture, disease, and therapeutics DOI Creative Commons

Binghan Zhou,

Wanling Lin,

Yaling Long

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: March 24, 2022

Abstract The NOTCH gene was identified approximately 110 years ago. Classical studies have revealed that signaling is an evolutionarily conserved pathway. receptors undergo three cleavages and translocate into the nucleus to regulate transcription of target genes. deeply participates in development homeostasis multiple tissues organs, aberration which results cancerous noncancerous diseases. However, recent indicate outcomes are changeable highly dependent on context. In terms cancers, can both promote inhibit tumor various types cancer. overall performance NOTCH-targeted therapies clinical trials has failed meet expectations. Additionally, mutation been proposed as a predictive biomarker for immune checkpoint blockade therapy many cancers. Collectively, pathway needs be integrally assessed with new perspectives inspire discoveries applications. this review, we focus classical latest findings related illustrate history, architecture, regulatory mechanisms, contributions physiological development, diseases, therapeutic applications microenvironment cancer immunotherapy also highlighted. We hope review will help not only beginners but experts systematically thoroughly understand

Language: Английский

Citations

664
The MYC oncogene — the grand orchestrator of cancer growth and immune evasion DOI
Renumathy Dhanasekaran, Anja Deutzmann, Wadie D. Mahauad‐Fernandez

et al.

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 19(1), P. 23 - 36

Published: Sept. 10, 2021

Language: Английский

Citations

578
Therapeutic targeting of “undruggable” MYC DOI
Víctor Llombart, Marc R. Mansour

EBioMedicine, Journal Year: 2021, Volume and Issue: 75, P. 103756 - 103756

Published: Dec. 20, 2021

Language: Английский

Citations

277
E3 ubiquitin ligases: styles, structures and functions DOI Creative Commons
Quan Yang,

Jinyao Zhao,

Dan Chen

et al.

Molecular Biomedicine, Journal Year: 2021, Volume and Issue: 2(1)

Published: July 29, 2021

Abstract E3 ubiquitin ligases are a large family of enzymes that join in three-enzyme ubiquitination cascade together with activating enzyme E1 and conjugating E2. play an essential role catalyzing the process transferring protein to attach lysine site targeted substrates. Importantly, modification is involved almost all life activities eukaryotes. Thus, might be regulating various biological processes cellular responses stress signal associated cancer development. Thanks their multi-functions, can promising target therapy. A deeper understanding regulatory mechanisms tumorigenesis will help find new prognostic markers accelerate growth anticancer therapeutic approaches. In general, we mainly introduce classifications important roles progression functions.

Language: Английский

Citations

225
Targeting Notch in oncology: the path forward DOI
Samarpan Majumder, Judy S. Crabtree, Todd E. Golde

et al.

Nature Reviews Drug Discovery, Journal Year: 2020, Volume and Issue: 20(2), P. 125 - 144

Published: Dec. 8, 2020

Language: Английский

Citations

210
LncRNAs in Ovarian Cancer Progression, Metastasis, and Main Pathways: ceRNA and Alternative Mechanisms DOI Open Access
Э. А. Брага, М. В. Фридман,

Alexey A. Moscovtsev

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(22), P. 8855 - 8855

Published: Nov. 23, 2020

Ovarian cancer (OvCa) develops asymptomatically until it reaches the advanced stages with metastasis, chemoresistance, and poor prognosis. Our review focuses on analysis of regulatory long non-coding RNAs (lncRNAs) competing protein-coding mRNAs for binding to miRNAs according model competitive endogenous RNA (ceRNA) in OvCa. Analysis publications showed that most lncRNAs acting as ceRNAs participate OvCa progression: migration, invasion, epithelial-mesenchymal transition (EMT), metastasis. More than 30 turned out be predictors survival and/or response therapy patients For a number oncogenic (CCAT1, HOTAIR, NEAT1, TUG1 among others) some suppressive lncRNAs, several lncRNA/miRNA/mRNA axes were identified, which revealed various functions each them. also considers examples alternative mechanisms actions besides being ceRNAs, including directly mRNA or protein, them (DANCR, GAS5, MALAT1, UCA1 act by both depending target protein. A systematic based data from literature Panther KEGG (Kyoto Encyclopedia Genes Genomes) databases significant part affects key pathways involved EMT, chemoresistance.

Language: Английский

Citations

197
CREBBP/EP300 mutations promoted tumor progression in diffuse large B-cell lymphoma through altering tumor-associated macrophage polarization via FBXW7-NOTCH-CCL2/CSF1 axis DOI Creative Commons

Yao‐Hui Huang,

Kun Cai,

Pengpeng Xu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Jan. 11, 2021

Abstract Epigenetic alterations play an important role in tumor progression of diffuse large B-cell lymphoma (DLBCL). However, the biological relevance epigenetic gene mutations on microenvironment remains to be determined. The core set genes relating histone methylation ( KMT2D , KMT2C EZH2 ), acetylation CREBBP EP300 DNA TET2 and chromatin remodeling ARID1A ) were detected training cohort 316 patients by whole-genome/exome sequencing (WGS/WES) validation 303 with newly diagnosed DLBCL targeted sequencing. Their correlation peripheral blood immune cells clinical outcomes assessed. Underlying mechanisms investigated both vitro vivo. Among all 619 patients, somatic (19.5%) most frequently observed, followed (8.7%), (8.4%), (8.2%), (7.8%), (6.8%), (2.9%). them, / significantly associated decreased absolute lymphocyte-to-monocyte ratios, as well inferior progression-free overall survival. In B-lymphoma cells, mutation or knockdown inhibited H3K27 acetylation, downregulated FBXW7 expression, activated NOTCH pathway, downstream CCL2/CSF1 resulting tumor-associated macrophage polarization M2 phenotype cell proliferation. murine models, xenografted tumors bearing presented lower higher recruitment, more rapid growth than those wild-type control via FBXW7-NOTCH-CCL2/CSF1 axis. Our work thus contributed understanding aberrant regulation alternative mechanism DLBCL.

Language: Английский

Citations

151
MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies DOI Creative Commons
Seyed Esmaeil Ahmadi,

Samira Rahimi,

Bahman Zarandi

et al.

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: Aug. 9, 2021

Abstract MYC oncogene is a transcription factor with wide array of functions affecting cellular activities such as cell cycle, apoptosis, DNA damage response, and hematopoiesis. Due to the multi-functionality MYC, its expression regulated at multiple levels. Deregulation this can give rise variety cancers. In review, regulation mechanisms by which adjusts implication in hematologic malignancies are summarized. Further, we also discuss potential inhibitors that could be beneficial for treating malignancies.

Language: Английский

Citations

144
Role of miRNA and lncRNAs in organ fibrosis and aging DOI Open Access
Soudeh Ghafouri‐Fard, Atefe Abak,

Seyedeh Fahimeh Talebi

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 143, P. 112132 - 112132

Published: Sept. 1, 2021

Fibrosis is the endpoint of pathological remodeling. This process contributes to pathogenesis several chronic disorders and aging-associated organ damage. Different molecular cascades contribute this process. TGF-β, WNT, YAP/TAZ signaling pathways have prominent roles in A number long non-coding RNAs microRNAs been found regulate fibrosis through modulation activity related pathways. miR-144-3p, miR-451, miR-200b, miR-328 are among that participate pathology cardiac fibrosis. Meanwhile, miR-34a, miR-17-5p, miR-122, miR-146a, miR-350 liver different situations. PVT1, MALAT1, GAS5, NRON, PFL, MIAT, HULC, ANRIL, H19 We review impact aging-related pathologies.

Language: Английский

Citations

120
Mechanical overloading promotes chondrocyte senescence and osteoarthritis development through downregulating FBXW7 DOI
Haiyan Zhang, Yan Shao,

Zihao Yao

et al.

Annals of the Rheumatic Diseases, Journal Year: 2022, Volume and Issue: 81(5), P. 676 - 686

Published: Jan. 20, 2022

To investigate the role of mechanical stress in cartilage ageing and identify mechanistic association during osteoarthritis (OA) progression.F-box WD repeat domain containing 7 (FBXW7) ubiquitin ligase expression chondrocyte senescence were examined vitro, experimental OA mice human cartilage. Mice with Fbxw7 knockout chondrocytes generated adenovirus-expressing (AAV-Fbxw7) was injected intra-articularly mice. Destabilised medial meniscus surgery performed to induce OA. Cartilage damage measured using Osteoarthritis Research Society International score changes determined. mRNA sequencing articular from control mice.Mechanical overloading accelerated cultured FBXW7 downregulated by primary cartilage, decreased patients OA, aged deletion induced catabolism mice, as manifested an upregulation p16INK4A, p21 Colx downregulation Col2a1 ACAN, which resulted exacerbation By contrast, intra-articular injection adenovirus expressing alleviated Mechanistically, transcription FBXW7-mediated MKK7 degradation, consequently stimulated JNK signalling. In particular, inhibition activity DTP3, a inhibitor, ameliorated degeneration CONCLUSIONS: is key factor between pathology

Language: Английский

Citations

117