RNA methylation‐related inhibitors: Biological basis and therapeutic potential for cancer therapy DOI Creative Commons

Huanxiang Chen,

Hongyang Liu,

Chenxing Zhang

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(4)

Published: April 1, 2024

Abstract RNA methylation is widespread in nature. Abnormal expression of proteins associated with strongly a number human diseases including cancer. Increasing evidence suggests that targeting holds promise for cancer treatment. This review specifically describes several common modifications, such as the relatively well‐studied N6‐methyladenosine, well 5‐methylcytosine and pseudouridine (Ψ). The regulatory factors involved these modifications their roles are also comprehensively discussed. We summarise diverse functions across different types RNAs. Furthermore, we elucidate structural characteristics along development specific inhibitors them. Additionally, recent advancements small molecule presented to underscore immense potential clinical significance enhancing therapeutic efficacy against Key Points In this paper, important related systematically summarised. Several modification were progression, relationships cell migration, invasion, drug resistance immune environment regulators have been proposed studies summarised detail, which great treatment future.

Language: Английский

Insights into N6-methyladenosine and programmed cell death in cancer DOI Creative Commons
Li Liu, Hui Li, Dingyu Hu

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Jan. 28, 2022

Abstract N6-methyladenosine (m6A) methylation, the most common form of internal RNA modification in eukaryotes, has gained increasing attention and become a hot research topic recent years. M6A plays multifunctional roles normal abnormal biological processes, its role may vary greatly depending on position m6A motif. Programmed cell death (PCD) includes apoptosis, autophagy, pyroptosis, necroptosis ferroptosis, which involve breakdown plasma membrane. Based implications methylation PCD, regulators functional were comprehensively studied reported. In this review, we focus high-complexity links between different types PCD pathways, are then closely associated with initiation, progression resistance cancer. Herein, clarifying relationship is great significance to provide novel strategies for cancer treatment, potential prospect clinical application.

Language: Английский

Citations

176
ALKBH5 Inhibited Cell Proliferation and Sensitized Bladder Cancer Cells to Cisplatin by m6A-CK2α-Mediated Glycolysis DOI Creative Commons
Hao Yu, Xiao Yang, Jinyuan Tang

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2020, Volume and Issue: 23, P. 27 - 41

Published: Oct. 23, 2020

N6-methyladenosine (m6A) is the most commonly occurring internal RNA modification to be found in eukaryotic mRNA and serves an important role various physiological events. AlkB homolog 5 demethylase (ALKBH5), m6A demethylase, belongs family of dioxygenases has been shown specifically demethylate RNA, which associated with a variety tumors. However, its function bladder cancer remains largely unclear. In present study, we that expression ALKBH5 was downregulated tissues cell lines. Low correlated worse prognosis patients. Furthermore, functional assays revealed knockdown promoted proliferation, migration, invasion, decreased cisplatin chemosensitivity 5637 T24 lines vivo vitro, whereas overexpression led opposite results. Finally, inhibited progression sensitized cells through casein kinase 2 (CK2)α-mediated glycolysis pathway m6A-dependent manner. Taken together, these findings might provide fresh insights into therapy.

Language: Английский

Citations

140
WTAP-mediated m6A modification of lncRNA DIAPH1-AS1 enhances its stability to facilitate nasopharyngeal carcinoma growth and metastasis DOI Open Access
Zhi‐Xuan Li,

Zi‐Qi Zheng,

Pan-Yang Yang

et al.

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: 29(6), P. 1137 - 1151

Published: Jan. 8, 2022

Language: Английский

Citations

127
Role of main RNA modifications in cancer: N6-methyladenosine, 5-methylcytosine, and pseudouridine DOI Creative Commons
Chen Xue,

Qingfei Chu,

Qiuxian Zheng

et al.

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

Published: April 28, 2022

Cancer is one of the major diseases threatening human life and health worldwide. Epigenetic modification refers to heritable changes in genetic material without any nucleic acid sequence results phenotypic changes. modifications regulate many biological processes, such as growth, aging, various diseases, including cancer. With advancement next-generation sequencing technology, role RNA cancer progression has become increasingly prominent a hot spot scientific research. This review studied several common modifications, N6-methyladenosine, 5-methylcytosine, pseudouridine. The deposition roles these coding noncoding RNAs are summarized detail. Based on background, this expression, function, underlying molecular mechanism their regulators further discussed some existing small-molecule inhibitors. More in-depth studies needed broaden understanding epigenetics diagnosis, treatment, prognosis.

Language: Английский

Citations

122
METTL3 enhances the stability of MALAT1 with the assistance of HuR via m6A modification and activates NF-κB to promote the malignant progression of IDH-wildtype glioma DOI
Yuzhou Chang, Ruichao Chai, Bo Pang

et al.

Cancer Letters, Journal Year: 2021, Volume and Issue: 511, P. 36 - 46

Published: April 29, 2021

Language: Английский

Citations

115
Recent advances in droplet microfluidics for single-cell analysis DOI
Zhenqi Jiang, Haoran Shi, Xiaoying Tang

et al.

TrAC Trends in Analytical Chemistry, Journal Year: 2023, Volume and Issue: 159, P. 116932 - 116932

Published: Jan. 13, 2023

Language: Английский

Citations

115
YTHDF1 promotes breast cancer cell growth, DNA damage repair and chemoresistance DOI Creative Commons
Yu Sun, Dan Dong, Yuhong Xia

et al.

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(3)

Published: March 12, 2022

Chemoresistance represents a major obstacle to the treatment of human cancers. Increased DNA repair capacity is one important mechanisms underlying chemoresistance. In silico analysis indicated that YTHDF1, an m6A binding protein, putative tumor promoter in breast cancer. Loss function studies further showed YTHDF1 promotes cancer cell growth vitro and vivo. facilitates S-phase entry, replication damage repair, accordingly knockdown sensitizes cells Adriamycin Cisplatin as well Olaparib, PARP inhibitor. E2F8 target molecule by which modulates mRNA stability METTL14-dependent manner. These data demonstrate has tumor-promoting role cancer, novel overcome

Language: Английский

Citations

91
Epigenetic modification of m6A regulator proteins in cancer DOI Creative Commons
Yumin Wang, Yan Wang, Harsh Patel

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: June 30, 2023

Divergent N6-methyladenosine (m6A) modifications are dynamic and reversible posttranscriptional RNA that mediated by m6A regulators or methylation regulators, i.e., methyltransferases ("writers"), demethylases ("erasers"), m6A-binding proteins ("readers"). Aberrant associated with cancer occurrence, development, progression, prognosis. Numerous studies have established aberrant function as either tumor suppressors oncogenes in multiple types. However, the functions mechanisms of remain largely elusive should be explored. Emerging suggest can modulated epigenetic modifications, namely, ubiquitination, SUMOylation, acetylation, methylation, phosphorylation, O-GlcNAcylation, ISGylation, lactylation via noncoding action, cancer. This review summarizes current roles The for modification genesis segregated. will improve understanding regulatory regulators.

Language: Английский

Citations

86
ALKBH5 activates FAK signaling through m6A demethylation in ITGB1 mRNA and enhances tumor-associated lymphangiogenesis and lymph node metastasis in ovarian cancer DOI Creative Commons
Rui Sun, Lin Yuan, Yi Jiang

et al.

Theranostics, Journal Year: 2023, Volume and Issue: 13(2), P. 833 - 848

Published: Jan. 1, 2023

Background: Lymph node (LN) metastasis is common in patients with epithelial ovarian cancer (EOC) and associated poor prognosis.Tumor-associated lymphangiogenesis the first stage of LN metastasis.Research on lymph metastases can help develop new anti-LN-targeted therapies.Aberrant N6-methyladenosine (m6A) modifications have been reported to be linked several cancers, however, their role EOC remains unclear.Methods: m6A levels tissues or without were evaluated by dot blot analysis.Real-time polymerase chain reaction (PCR) immunofluorescence used examine expression m6A-related enzymes.Additionally, vitro vivo functional studies performed discover importance AlkB homolog 5 (ALKBH5) gene lymphatic metastasis.To identify downstream target genes regulated ALKBH5, we RNA pulldown, RNA-binding protein immunoprecipitation-quantitative PCR, co-immunoprecipitation, m6A-modified luciferase reporter assays.Results: modification was reduced cancers metastases.ALKBH5 overexpression increased tumor-associated both vivo.ALKBH5 also reversed ITGB1 mRNA suppressed YTHDF2 protein-mediated m6A-dependent degradation, which resulted phosphorylation focal adhesion kinase (FAK) Src proto-oncogene proteins, thereby increasing metastasis.Furthermore, hypoxia induced inducible factor 1 subunit alpha, ALKBH5 enhanced EOC. Conclusions:The ALKBH5/m6A-ITGB1/FAK signalling axis important metastasis.Antibodies that block FAK kinase-inhibitors are promising anti-metastatic agents.

Language: Английский

Citations

49
The role of tumor-associated macrophages in tumor immune evasion DOI Creative Commons

Ruizhe Huang,

Ting Kang, Siyu Chen

et al.

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(5)

Published: May 7, 2024

Abstract Background Tumor growth is closely linked to the activities of various cells in tumor microenvironment (TME), particularly immune cells. During progression, circulating monocytes and macrophages are recruited, altering TME accelerating growth. These adjust their functions response signals from stromal Tumor-associated (TAMs), similar M2 macrophages, key regulators TME. Methods We review origins, characteristics, TAMs within This analysis includes mechanisms through which facilitate evasion promote metastasis. Additionally, we explore potential therapeutic strategies that target TAMs. Results instrumental mediating malignant behaviors. They release cytokines inhibit effector attract additional immunosuppressive primarily T cells, inducing exhaustion directly, influencing activity indirectly cellular interactions, or suppressing checkpoints. directly involved proliferation, angiogenesis, invasion, Summary Developing innovative tumor-targeted therapies immunotherapeutic currently a promising focus oncology. Given pivotal role evasion, several approaches have been devised them. include leveraging epigenetics, metabolic reprogramming, engineering repolarize TAMs, inhibiting recruitment activity, using as drug delivery vehicles. Although some these remain distant clinical application, believe future targeting will offer significant benefits cancer patients.

Language: Английский

Citations

47