YTHDF3 modulates the progression of breast cancer cells by regulating FGF2 through m6A methylation DOI Creative Commons

RF Gong,

ZH Zhang,

Ting Sun

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Дек. 14, 2023

Abstract Background Breast cancer (BC) is a prevailing malignancy among women, and its inconspicuous development contributes significantly to mortality. The RNA N6-methyladenosine (m 6 A) modification represents an emerging mechanism for gene expression regulation, with the active involvement of YTH binding protein 3 (YTHDF3) in tumor progression across multiple types. Nonetheless, precise function breast necessitates further investigation. Methods YTHDF3 both cell lines patient tissues was examined using Western blotting, reverse transcription quantitative PCR (RT-qPCR), immunohistochemistry (IHC) techniques. Bioinformatics analysis methylated immunoprecipitation sequencing (MeRIP-seq) transcriptome (RNA-seq) data employed screen target genes YTHDF3. main focus this study investigate vitro biological functions specific correlation m A methylation were studied through pull-down, immunoprecipitation, co-immunoprecipitation experiments. regulatory mechanisms downstream assessed stability analysis. Furthermore, cells validated CRISPR-Cas9 technology rescue Results By constructing risk model TCGA database, identified as high-risk factor factors. Subsequent investigations revealed elevated various subtypes cancer, accompanied by poor prognosis. MeRIP-seq fibroblast growth 2 (FGF2) Knockdown led significant inhibition self-renewal, migration, invasion abilities vitro. Mechanistically, specifically recognized transcript FGF2 within coding sequence (CDS) region, leading degradation. Moreover, depletion markedly suppressed cells, while reducing YTHDF3-overexpressing substantially alleviated malignant progression. Conclusions In summary, our elucidates role oncogene maintaining BC A-dependent mechanism. Additionally, we provide potential biomarker panel prognostic prediction BC.

Язык: Английский

The roles of m6A methylation in cervical cancer: functions, molecular mechanisms, and clinical applications DOI Creative Commons

Zhonghao Mao,

Bingyu Wang,

Teng Zhang

и другие.

Cell Death and Disease, Год журнала: 2023, Номер 14(11)

Опубликована: Ноя. 11, 2023

Abstract Cervical cancer (CC) is a gynecological neoplasm with the highest incidence rate, primarily attributed to persistent infection of high-risk Human papillomavirus (HPV). Despite extensive research, pathogenesis CC remains unclear. N6-methyladenosine (m6A) methylation, most prevalent form epigenetic modification in RNA, intricately linked cell proliferation, metastasis, metabolism, and therapeutic resistance within tumor microenvironment (TME) CC. The involvement writer, reader, eraser m6A impacts advancement tumors through regulation RNA stability, nuclear export, translation efficiency, degradation. Here, we discuss biogenesis m6A, atypical expressions regulators, mechanisms molecular interactions, their functions Furthermore, elucidate non-coding RNA. In context precision medicine, advancements genomics, proteomics, high-throughput sequencing technologies, summarize application clinical diagnosis treatment Additionally, new perspectives on detection methods, immune regulation, nano-drug development are presented, which lay foundation for further research provide ideas

Язык: Английский

Процитировано

22
The research progress on radiation resistance of cervical cancer DOI Creative Commons

Мейли Лианг,

Liying Sheng,

Yumin Ke

и другие.

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Апрель 8, 2024

Cervical carcinoma is the most prevalent gynecology malignant tumor and ranks as fourth common cancer worldwide, thus posing a significant threat to lives health of women. Advanced early-stage cervical patients with high-risk factors require adjuvant treatment following surgery, radiotherapy being primary approach. However, tolerance has become major obstacle in its treatment. Recent studies have demonstrated that radiation resistance closely associated DNA damage repair pathways, microenvironment, stem cells, hypoxia, cell cycle arrest, epigenetic mechanisms, among other factors. The development involves complex interactions between multiple genes, wherein each factor interacts through one or more signaling pathways. This paper provides an overview research progress on understanding mechanism underlying cancer.

Язык: Английский

Процитировано

6
Regulation of m6A modification on ferroptosis and its potential significance in radiosensitization DOI Creative Commons
Xun Chen, Lejia Zhang,

Yi He

и другие.

Cell Death Discovery, Год журнала: 2023, Номер 9(1)

Опубликована: Сен. 15, 2023

Abstract Radiotherapy is often used to treat various types of cancers, but radioresistance greatly limits the clinical efficiency. Recent studies have shown that radiotherapy can lead ferroptotic cancer cell deaths. Ferroptosis a new type programmed death caused by excessive lipid peroxidation. The induction ferroptosis provides potential therapeutic strategy for radioresistance. As most common post-transcriptional modification mRNA, m 6 A methylation widely involved in regulation physiopathological processes regulating RNA function. Dynamic controlled regulatory factors also affects susceptibility cells ferroptosis, thereby determining radiosensitivity tumor radiotherapy. In this review, we summarize mechanism and significance induced analyze characteristics on discuss possibility radiosensitization enhancing A-mediated ferroptosis. Clarifying its response will help us identify novel targets improve efficacy reduce or overcome

Язык: Английский

Процитировано

14
Targeting RNA modifications with pharmacological agents: New frontiers in cancer therapy DOI Creative Commons
Angel Guan, Justin Wong

Cancer Medicine, Год журнала: 2024, Номер 13(7)

Опубликована: Март 28, 2024

Abstract The N6‐methyladenosine (m6A) RNA modification has gained significant prominence as a new layer of regulatory mechanism that governs gene expression. Over the past decade, various m6A regulators responsible for introducing, eliminating, and recognising methylation have been identified. Notably, these often exhibit altered expression patterns in cancer, occasionally offering prognostic value. Nonetheless, complex roles human cancer pathology remain enigmatic, with conflicting outcomes reported different studies.In recent years, multitude inhibitors activators targeting reported. Several compounds demonstrated promising efficacy both vitro vivo models. These findings collectively underscore dynamic landscape regulation biology, revealing its potential therapeutic target indicator.

Язык: Английский

Процитировано

4
Decoding intricate interactions between m6A modification with mRNAs and non-coding RNAs in cervical cancer: Molecular mechanisms and clinical implications DOI
Xuefei Liu, Lizhi Zhang, Ji Chen

и другие.

Cellular Signalling, Год журнала: 2025, Номер unknown, С. 111745 - 111745

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
YTHDF3 modulates the progression of breast cancer cells by regulating FGF2 through m6A methylation DOI Creative Commons
Rongfang Gong,

Z. H. Zhang,

Tung‐Tien Sun

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Сен. 20, 2024

Introduction Breast cancer (BC) is a prevailing malignancy among women, and its inconspicuous development contributes significantly to mortality. The RNA N6-methyladenosine (m 6 A) modification represents an emerging mechanism for gene expression regulation, with the active involvement of YTH binding protein 3 (YTHDF3) in tumor progression across multiple types. Nonetheless, precise function breast necessitates further investigation. Methods YTHDF3 both cell lines patient tissues was examined using Western blotting, reverse transcription quantitative PCR (RT-qPCR), immunohistochemistry (IHC) techniques. Bioinformatics analysis methylated immunoprecipitation sequencing (MeRIP-seq) transcriptome (RNA-seq) data employed screen target genes YTHDF3. main focus this study investigate vitro biological functions specific correlation m A methylation were studied through pull-down, immunoprecipitation, co-immunoprecipitation experiments. regulatory mechanisms downstream assessed stability analysis. Furthermore, cells validated CRISPR-Cas9 technology rescue Results By constructing risk model TCGA database, identified as high-risk factor factors. Subsequent investigations revealed elevated various subtypes cancer, accompanied by poor prognosis. MeRIP-seq fibroblast growth 2 (FGF2) Knockdown led significant inhibition self-renewal, migration, invasion abilities . Mechanistically, specifically recognized transcript FGF2 within coding sequence (CDS) region, leading degradation. Moreover, depletion markedly suppressed cells, while reducing YTHDF3-overexpressing substantially alleviated malignant progression. Conclusions In summary, our elucidates role oncogene maintaining BC A-dependent mechanism. Additionally, we provide potential biomarker panel prognostic prediction BC.

Язык: Английский

Процитировано

3
ZC3H13 Enhances the Malignancy of Cervical Cancer by Regulating m6A Modification of CKAP2 DOI

Yuan Zhang,

Xiaohong Chen,

Huiqun Chen

и другие.

Critical Reviews in Immunology, Год журнала: 2023, Номер 43(6), С. 1 - 13

Опубликована: Янв. 1, 2023

Sustained expression of zinc finger CCCH-type containing 13 (ZC3H13) in tumors is essential for cancer cell malignancy; however, our understanding its clinical effects and mechanisms cervical (CC) limited. In this study, we aimed to reveal the effect on CC progression ZC3H13-mediated N6-methyladenosine (m6A) modification stabilize cytoskeleton-associated protein 2 (CKAP2) expression. tissues paired adjacent normal were collected from 50 patients. qRT-PCR was used clarify ZC3H13 CKAP2 levels tissues. The functional roles analyzed by detecting changes proliferation, migration, invasion, tumor growth vivo. regulatory relationship between investigated confirming m6A their correlation. highly expressed linked with poor prognosis. We observed that inhibition decreased while facilitation promoted malignancy. mediated enhance cells. Furthermore, overexpression partially restored malignant phenotypic promotion induced summary, study revealed ZC3H13-mediating promotes development. This finding should be conducive an role ZC3H13-m6A-CKAP2 provide effective therapeutic target cancer.

Язык: Английский

Процитировано

8
Examining the evidence for mutual modulation between m6A modification and circular RNAs: current knowledge and future prospects DOI Creative Commons

Xiaozhu Tang,

Mengjie Guo,

Yuanjiao Zhang

и другие.

Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)

Опубликована: Авг. 3, 2024

Abstract The resistance of cancer cells to treatment significantly impedes the success therapy, leading recurrence various types cancers. Understanding specific mechanisms therapy may offer novel approaches for alleviating drug in cancer. Recent research has shown a reciprocal relationship between circular RNAs (circRNAs) and N6-methyladenosine (m6A) modification, their interaction can affect sensitivity therapy. This review aims summarize latest developments m6A modification circRNAs importance regulating Furthermore, we explore mutual exact provide insights into potential future reversing resistance.

Язык: Английский

Процитировано

2
Epitranscriptomics and cervical cancer: the emerging role of m6A, m5C and m1A RNA modifications DOI
Akshat D. Modi,

Hira Zahid,

Ashlyn Chase Southerland

и другие.

Expert Reviews in Molecular Medicine, Год журнала: 2024, Номер 26

Опубликована: Янв. 1, 2024

Abstract Cervical cancer (CC), one of the most prevalent and detrimental gynaecologic cancers, evolves through genetic epigenetic alterations resulting in promotion oncogenic activity dysfunction tumour-suppressing mechanisms. Despite medical advancement, prognosis for advanced-stage patients remains extremely low due to high recurrence rates resistance existing treatments. Thereby, search potential prognostic biomarkers is heightened unravel new modalities CC pathogenesis develop novel anti-cancer therapies. Epitranscriptomic modifications, reversible RNA regulate various biological processes by deciding fate mediating interactions. This narrative review provides insight into cellular molecular roles endogenous RNA-editing proteins their associated epitranscriptomic especially N 6 -methyladenosine (m A), 5-methylcytosine 5 C) 1 governing development, progression metastasis CC. We discussed in-depth mechanisms underlying regulation over 50 RNAs responsible tumorigenesis, proliferation, migration, invasion, survival, autophagy, stemness, epithelial-mesenchymal transition, metabolism (glucose, lipid, glutamate glutamine), (drug radiation), angiogenesis Additionally, we provided a concise overview therapeutic targeting altered expression aberrant deposition modifications on both coding non-coding

Язык: Английский

Процитировано

2
N6-Methyladenosine-Modified LEAWBIH Drives Hepatocellular Carcinoma Progression through Epigenetically Activating Wnt/β-Catenin Signaling DOI Creative Commons
Huamei Wei,

Lizheng Huang,

Qi Lu

и другие.

Journal of Hepatocellular Carcinoma, Год журнала: 2023, Номер Volume 10, С. 1991 - 2007

Опубликована: Ноя. 1, 2023

N6-methyladenosine (m6A) modification plays an important role in regulating RNA maturation, stability, and translation. Thus, m6A is involved various pathophysiological processes including hepatocellular carcinoma (HCC). However, the direct contribution of modifications to function HCC remains unclear. Here, we identified LEAWBIH (long non-coding epigenetically activating Wnt/β-catenin signalling HCC) as m6A-modified long (lncRNA) investigated effects on HCC.Quantitative polymerase chain reaction was performed measure gene expression tissues cells. The level detected using a methylated immunoprecipitation assay single-base elongation- ligation-based qPCR amplification method. Cell proliferation evaluated Glo cell viability CCK-8 assays. migration invasion were Transwell mechanisms modified chromatin isolation by purification, immunoprecipitation, dual-luciferase reporter assays.LEAWBIH highly expressed correlated with poor survival patients. transcript. increased transcript stability. HCC, high predicted survival. promotes proliferation, migration, modification-dependent manner. Mechanistic investigations revealed that activated signaling. binds reader YTHDC1, which further interacts recruits H3K9me2 demethylase KDM3B CTNNB1 promoter, leading demethylation transcription activation. Functional rescue assays showed blocking signaling abolished HCC.m6A-modified exerts oncogenic signaling, highlighting promising therapeutic target for HCC.

Язык: Английский

Процитировано

6