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

m6A Modification in Coding and Non-coding RNAs: Roles and Therapeutic Implications in Cancer DOI Creative Commons
Huilin Huang, Hengyou Weng, Jianjun Chen

et al.

Cancer Cell, Journal Year: 2020, Volume and Issue: 37(3), P. 270 - 288

Published: March 1, 2020

Language: Английский

Citations

940
The potential role of RNA N6-methyladenosine in Cancer progression DOI Creative Commons
Tianyi Wang,

Shan Kong,

Mei Tao

et al.

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: May 12, 2020

Abstract N6-methyladenosine (m6A) is considered the most common, abundant, and conserved internal transcript modification, especially in eukaryotic messenger RNA (mRNA). m6A installed by methyltransferases (METTL3/14, WTAP, RBM15/15B, VIRMA ZC3H13, termed “writers”), removed demethylases (FTO, ALKBH5, ALKBH3, “erasers”), recognized m6A-binding proteins (YTHDC1/2, YTHDF1/2/3, IGF2BP1/2/3, HNRNP, eIF3, “readers”). Accumulating evidence suggests that methylation greatly impacts metabolism involved pathogenesis of many kinds diseases, including cancers. In this review, we focus on physiological functions modification its related regulators, as well potential biological roles these elements human tumors.

Language: Английский

Citations

800
The role of m6A RNA methylation in cancer metabolism DOI Creative Commons
Yuanyuan An, Hua Duan

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

Published: Jan. 12, 2022

Abstract Metabolic reprogramming is one of the main characteristics malignant tumors, which due to flexible changes cell metabolism that can meet needs growth and maintain homeostasis tissue environments. Cancer cells obtain metabolic adaptation through a variety endogenous exogenous signaling pathways, not only promote cancer cells, but also start transformation process adapt tumor microenvironment. Studies show m6A RNA methylation widely involved in recombination cells. In eukaryotes, most abundant modification mRNA, almost all cycle stages, including regulation transcription, maturation, translation, degradation stability mRNA. M6A be physiological pathological processes, cancer. this review, we discuss role plays metabolism-related molecules aiming importance targeting regulating metabolism.

Language: Английский

Citations

483
Roles of METTL3 in cancer: mechanisms and therapeutic targeting DOI Creative Commons
Chengwu Zeng, Wanxu Huang, Yangqiu Li

et al.

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

Published: Aug. 27, 2020

N6-methyladenosine (m6A) is the most abundant mRNA modification and catalyzed by methyltransferase complex, in which methyltransferase-like 3 (METTL3) sole catalytic subunit. Accumulating evidence recent years reveals that METTL3 plays key roles a variety of cancer types, either dependent or independent on its m6A RNA activity. While modifications have been extensively reviewed elsewhere, critical functions various types cancer, as well potential targeting treatment, not yet highlighted. Here we summarize our current understanding both oncogenic tumor-suppressive METTL3, underlying molecular mechanisms. The well-documented protein structure METTL3/METTL14 heterodimer provides basis for therapeutic targeting, also discussed this review.

Language: Английский

Citations

425
The role of m6A, m5C and Ψ RNA modifications in cancer: Novel therapeutic opportunities DOI Creative Commons

Paz Nombela,

Borja Miguel‐López, Sandra Blanco

et al.

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Jan. 18, 2021

Abstract RNA modifications have recently emerged as critical posttranscriptional regulators of gene expression programmes. Significant advances been made in understanding the functional role regulating coding and non-coding processing function, which turn thoroughly shape distinct They affect diverse biological processes, correct deposition many these is required for normal development. Alterations their are implicated several diseases, including cancer. In this Review, we focus on occurrence N 6 -methyladenosine (m A), 5-methylcytosine 5 C) pseudouridine (Ψ) RNAs describe physiopathological We will highlight latest insights into mechanisms how influence tumour development, maintenance, progression. Finally, summarize development small molecule inhibitors that target specific writers or erasers to rewind epitranscriptome a cancer cell therapeutic potential.

Language: Английский

Citations

358
METTL3/IGF2BP3 axis inhibits tumor immune surveillance by upregulating N6-methyladenosine modification of PD-L1 mRNA in breast cancer DOI Creative Commons
Weijun Wan, Xiang Ao, Quan Chen

et al.

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

Published: Feb. 23, 2022

Abstract Background Continual expression of PD-L1 in tumor cells is critical for immune escape and host T cell exhaustion, however, knowledge on its clinical benefits through inhibition limited breast cancer. N 6 -methyladenosine (m A) plays a crucial role multiple biological activities. Our study aimed to investigate the regulatory m A modification surveillance Methods MeRIP-seq epitranscriptomic microarray identified that downstream target METTL3. MeRIP-qPCR, absolute quantification assay, RIP-qPCR were used examine molecular mechanism underlying METTL3/m A/IGF2BP3 signaling axis expression. B-NDG BALB/c mice construct xenograft models verify phenotypes upon METTL3 IGF2BP3 silencing. In addition, cancer tissue was analyze correlation between or Results We METTL3-mediated cells. knockdown significantly abolished reduced stabilization mRNA. Additionally, mRNA activation A-IGF2BP3-dependent. Moreover, enhanced anti-tumor immunity PD-L1-mediated activation, infiltration both vitro vivo. also positively correlated with tissues. Conclusion suggested could post-transcriptionally upregulate an A-IGF2BP3-dependent manner further promote mRNA, which may have important implications new efficient therapeutic strategies immunotherapy.

Language: Английский

Citations

276
m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2–mediated YAP activity in NSCLC DOI Creative Commons

Dan Jin,

Jiwei Guo, Yan Wu

et al.

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: Feb. 27, 2020

The importance of mRNA methylation erased by ALKBH5 in biogenesis, decay, and translation control is an emerging research focus. Ectopically activated YAP associated with the development many human cancers. However, mechanism whereby regulates expression activity to inhibit NSCLC tumor growth metastasis not clear.Protein transcript interactions were analyzed normal lung cell cells. Gene was evaluated qPCR reporter assays. Protein levels determined immunochemical approaches. Nucleic acid status immunoprecipitation. Cell behavior standard biochemical tests. m6A modification MeRIP.Our results show that negatively correlated plays opposite role regulation cellular proliferation, invasion, migration, EMT reduced YAP. YTHDF3 combined pre-mRNA depending on modification. YTHDF1 YTHDF2 competitively interacted m6A-independent manner regulate expression. facilitated decay via AGO2 system, whereas promoted interacting eIF3a; both these activities are regulated Furthermore, decreased regulating miR-107/LATS2 axis HuR-dependent manner. Further, inhibited vivo reducing YAP.The presented findings suggest demethylase inhibits YTHDFs-mediated inhibiting miR-107/LATS2-mediated NSCLC. Moreover, effective inhibition might constitute a potential treatment strategy for cancer.

Language: Английский

Citations

275
Diagnostic, prognostic, and therapeutic significance of long non-coding RNA MALAT1 in cancer DOI

Bela Goyal,

Shashi Ranjan Mani Yadav, Nikee Awasthee

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2021, Volume and Issue: 1875(2), P. 188502 - 188502

Published: Jan. 11, 2021

Language: Английский

Citations

269
METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer DOI Creative Commons
Xiaoxiang Chen, Mu Xu,

Xueni Xu

et al.

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: June 17, 2020

Colorectal cancer (CRC) is one of the leading causes tumor-related death worldwide, and its main cause distant metastasis. Methyltransferase-like 14(METTL14), a major RNA N6-adenosine methyltransferase, involved in tumor progression via regulating function. The goal study to uncover biological function molecular mechanism METTL14 CRC.Quantitative real-time PCR (qRT-PCR), western blot immunohistochemical (IHC) assays were employed detect SOX4 CRC cell lines tissues. functions demonstrated using vitro vivo experiments. Chromatin immunoprecipitation (ChIP), Transcrptomic sequencing (RNA-Seq), m6A-RNA (MeRIP-Seq), luciferase reporter used explore action.METTL14 expression was significantly downregulated decreased associated with poor overall survival (OS). Both univariate multivariate Cox regression analysis indicated that an independent prognostic factor CRC. Moreover, lysine-specific histone demethylase 5C(KDM5C)-mediated demethylation H3 lysine 4 tri-methylation(H3K4me3) promoter inhibited transcription. Functionally, we verified cells migration, invasion metastasis through assays, respectively. Furthermore, identified SRY-related high-mobility-group box 4(SOX4) as target METTL14-mediated m6A modification. Knockdown markedly abolished mRNA modification elevated expression. We also revealed degradation relied on YTHDF2-dependent pathway. Lastly, might inhibit malignant process partly SOX4-mediated EMT PI3K/Akt signals.Decreased facilitates CRC, suggesting be potential biomarker effective therapeutic for

Language: Английский

Citations

265
m6A modification: recent advances, anticancer targeted drug discovery and beyond DOI Creative Commons
Lijuan Deng,

Wei-Qing Deng,

Shu-Ran Fan

et al.

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

Published: Feb. 14, 2022

Abstract Abnormal N6-methyladenosine (m6A) modification is closely associated with the occurrence, development, progression and prognosis of cancer, aberrant m6A regulators have been identified as novel anticancer drug targets. Both traditional medicine-related approaches modern discovery platforms used in an attempt to develop m6A-targeted drugs. Here, we provide update latest findings on critical roles cancer progression, summarize rational sources for agents from medicines computer-based chemosynthetic compounds. This review highlights potential targeting treatment proposes advantage artificial intelligence (AI) m6A-targeting Graphical abstract Three stages discovery: medicine-based natural products, chemical or synthesis, (AI)-assisted future.

Language: Английский

Citations

262