Mass Spectrometry-Based Pipeline for Identifying RNA Modifications Involved in a Functional Process: Application to Cancer Cell Adaptation DOI Creative Commons
Amandine Amalric,

Aurore Attina,

Amandine Bastide

et al.

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(5), P. 1825 - 1833

Published: Jan. 26, 2024

Cancer onset and progression are known to be regulated by genetic epigenetic events, including RNA modifications (a.k.a. epitranscriptomics). So far, more than 150 chemical have been described in all subtypes, messenger, ribosomal, transfer RNAs. their regulators implicated steps of post-transcriptional regulation. The dysregulation this complex yet delicate balance can contribute disease evolution, particularly the context carcinogenesis, where cells subjected various stresses. We sought discover involved cancer cell adaptation inhospitable environments, a peculiar feature stem (CSCs). were interested marks that help suspension culture, which is often used as surrogate evaluate tumorigenic potential. For purpose, we designed an experimental pipeline consisting four steps: (1) culture different growth conditions favor CSC survival; (2) simultaneous subtype (mRNA, rRNA, tRNA) enrichment hydrolysis; (3) multiplex analysis nucleosides LC-MS/MS followed statistical/bioinformatic analysis; (4) functional validation identified marks. This study demonstrates modification landscape evolves along with phenotype under constraints. Remarkably, discovered short epitranscriptomic signature, conserved across colorectal lines associated CSCs. Functional tests confirmed importance selected process confirming validity our approach opening up interesting prospects field.

Language: Английский

5-Methylcytosine transferase NSUN2 drives NRF2-mediated ferroptosis resistance in non-small cell lung cancer DOI Creative Commons
Youming Chen,

Zuli Jiang,

Chenxing Zhang

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(4), P. 106793 - 106793

Published: Feb. 24, 2024

RNA 5-methylcytosine (m5C) is an abundant chemical modification in mammalian RNAs and plays crucial roles regulating vital physiological pathological processes, especially cancer. However, the dysregulation of m5C its underlying mechanisms non-small cell lung cancer (NSCLC) remain unclear. Here we identified that NSUN2, a key methyltransferase, highly expressed NSCLC tumor tissue. We found elevated NSUN2 expression levels strongly correlate with grade size, predicting poor outcomes for patients. Furthermore, RNA-seq subsequent confirmation studies revealed antioxidant-promoting transcription factor NRF2 target depleting decreases increases sensitivity cells to ferroptosis activators both vitro vivo. Intriguingly, methylated-RIP-qPCR assay results indicated mRNA has higher level when overexpressed but shows no significant changes methyltransferase-deficient group. Mechanistically, confirmed upregulates by enhancing stability through within 5'UTR region recognized specific reader protein YBX1, rather than influencing translation. In rescue experiments, show knocking down diminished proliferation, migration, tolerance mediated overexpression. conclusion, our study unveils novel regulatory mechanism which sustains m5C-YBX1-axis, suggesting targeting regulated pathway might offer promising therapeutic strategies

Language: Английский

Citations

20
Writers, readers, and erasers RNA modifications and drug resistance in cancer DOI Creative Commons
Di Chen, Xinyu Gu,

Yeltai Nurzat

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 30, 2024

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.

Language: Английский

Citations

18
LINC02159 promotes non-small cell lung cancer progression via ALYREF/YAP1 signaling DOI Creative Commons

Yang Qiu-rong,

Maoye Wang,

Jing Xu

et al.

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

Published: Aug. 4, 2023

Lung cancer is the leading cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) have emerged as key regulators development and progression, promising biomarkers for diagnosis prognosis cancer. In this study, we identified a new lncRNA (LINC02159) that was upregulated in tumor tissues serum non-small cell lung (NSCLC) patients. We demonstrated knockdown LINC02159 inhibited NSCLC proliferation, migration, invasion, but induced apoptosis cycle arrest vitro retarded growth vivo, while overexpression led to opposite effect. discovered highly correlated with metastasis-related pathways by using transcriptomic analysis YAP1 potential target gene LINC02159. Mechanistically, bound Aly/REF export factor (ALYREF) enhance stability messenger RNA (mRNA) via m5C modification, which activation Hippo β-catenin signaling cells. Rescue experiments showed LINC01259 promoted progression YAP1- ALYREF-dependent manner. conclusion, plays an oncogenic role regulating ALYREF/YAP1 signaling, it has be utilized diagnostic marker therapeutic NSCLC.

Language: Английский

Citations

41
Epigenetic inactivation of the 5-methylcytosine RNA methyltransferase NSUN7 is associated with clinical outcome and therapeutic vulnerability in liver cancer DOI Creative Commons
Vanessa Ortiz-Barahona, Marta Soler, Verónica Dávalos

et al.

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

Published: May 12, 2023

RNA modifications are important regulators of transcript activity and an increasingly emerging body data suggests that the epitranscriptome its associated enzymes altered in human tumors.

Language: Английский

Citations

31
tRNA Modifications and Modifying Enzymes in Disease, the Potential Therapeutic Targets DOI Creative Commons

Weifang Cui,

Deze Zhao, Junjie Jiang

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(4), P. 1146 - 1162

Published: Jan. 1, 2023

tRNA is one of the most conserved and abundant RNA species, which plays a key role during protein translation.tRNA molecules are post-transcriptionally modified by modifying enzymes.Since high-throughput sequencing technology has developed rapidly, modification types have been discovered in many research fields.In tRNA, numerous modifications enzymes implicated biological functions human diseases.In our review, we talk about relevant modifications, including stability, translation, cell cycle, oxidative stress, immunity.We also explore how contribute to progression diseases.Based on previous studies, discuss some emerging techniques for assessing aid discovering different modifications.

Language: Английский

Citations

24
An Overview of Current Detection Methods for RNA Methylation DOI Open Access
Buket Sağlam, Bünyamin Akgül

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3098 - 3098

Published: March 7, 2024

Epitranscriptomic mechanisms, which constitute an important layer in post-transcriptional gene regulation, are involved numerous cellular processes under health and disease such as stem cell development or cancer. Among various RNA methylation is considered to have vital roles eukaryotes primarily due its dynamic reversible nature. There methylations that include, but not limited to, 2'-O-dimethyladenosine (m6Am), N7-methylguanosine (m7G), N6-methyladenosine (m6A) N1-methyladenosine (m1A). These biochemical modifications modulate the fate of by affecting translation, target site determination, processing, polyadenylation, splicing, structure, editing stability. Thus, it highly quantitatively measure changes marks gain insight into disease. Although there complicating challenges identifying certain genome wide, methods been developed recently facilitate quantitative measurement methylated RNAs. To this end, detection for can be classified five categories antibody-based, digestion-based, ligation-based, hybridization-based direct RNA-based methods. In review, we aimed summarize our current understanding methylation, highlighting their advantages disadvantages, along with field.

Language: Английский

Citations

16
Molecular insights into regulatory RNAs in the cellular machinery DOI Creative Commons
Sumin Yang, Sung-Hyun Kim, Eun-Jeong Yang

et al.

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(6), P. 1235 - 1249

Published: June 14, 2024

It is apparent that various functional units within the cellular machinery are derived from RNAs. The evolution of sequencing techniques has resulted in significant insights into approaches for transcriptome studies. Organisms utilize RNA to govern systems, and a heterogeneous class RNAs involved regulatory functions. In particular, increasingly recognized participate intricately functioning across almost all levels biological systems. These systems include those mediating chromatin arrangement, transcription, suborganelle stabilization, posttranscriptional modifications. Any exhibiting activity can be termed typically represented by noncoding RNAs, which constitute substantial portion genome. function based on principle structural changes through cis and/or trans regulation facilitate mutual RNA‒RNA, RNA‒DNA, RNA‒protein interactions. not been clearly elucidated whether identified deep actually anticipated mechanisms. This review addresses dominant properties at layers covers activities, dynamics, modifications, associated molecules, further challenges related therapeutics learning.

Language: Английский

Citations

12
Long noncoding RNA H19: functions and mechanisms in regulating programmed cell death in cancer DOI Creative Commons

Yuyang Xia,

Tianjiao Pei,

Junjie Zhao

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Feb. 14, 2024

Long noncoding RNAs (lncRNAs) are a group of with transcript lengths >200 nucleotides. Mounting evidence suggests that lncRNAs closely associated tumorigenesis. LncRNA H19 (H19) was the first lncRNA to function as an oncogene in many malignant tumors. Apart from established role promoting cell growth, proliferation, invasion, migration, epithelial-mesenchymal transition (EMT), and metastasis, it has been recently discovered also inhibits programmed death (PCD) cancer cells. In this review, we summarize mechanisms by which regulates PCD cells through various signaling pathways, molecular mechanisms, epigenetic modifications. Wnt/β-catenin pathway PI3K-Akt-mTOR pathway. It acts competitive endogenous RNA (ceRNA) regulation. The interaction between RNA-binding proteins (RBP) apoptosis cancer. Moreover, modifications, including DNA methylation histone involved H19-associated conclusion, via chemoresistance, highlighting promising research significance therapeutic target. We hope our study will contribute broader understanding development treatment.

Language: Английский

Citations

11
N-acetyltransferase 10 impedes EZH2/H3K27me3/GABARAP axis mediated autophagy and facilitates lung cancer tumorigenesis through enhancing SGK2 mRNA acetylation DOI
Nan Xiao, Hongyang Liu, Ruike Zhang

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 139823 - 139823

Published: Jan. 1, 2025

Language: Английский

Citations

1
NAT10 Promotes Gastric Cancer Liver Metastasis by Modulation of M2 Macrophage Polarization and Metastatic Tumor Cell Hepatic Adhesion DOI Creative Commons
Chen Chen, Zhangding Wang, Qingfeng Lin

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 22, 2025

Abstract The relationship between patterns of RNA modifications and gastric cancer (GC) liver metastasis (GCLM) remains unclear. Here, by single‐cell sequencing, clinical sample analysis, mouse model studies, an abnormal increase in the expression acetyltransferase N‐acetyltransferase 10 (NAT10) metastatic GC cells is identified. NAT10‐mediated N4‐acetylcytidine modification CXCL2 KLF5 mRNA increases their stability. Then, secreted found to promote infiltration polarization M2‐like macrophages produce oncostatin M, which transcriptionally activates NAT10 via STAT3 signaling. In addition, organoid models confirm that promotes adhesion hepatocytes. Mechanistically, ITGαV, facilitating cell attachment Intriguingly, high NAT10/KLF5 axis associated with poor prognosis patients targeting this significantly reduces GCLM preclinical murine models. Collectively, these findings suggest significance developing targeted therapies for metastasis.

Language: Английский

Citations

1