Novel insights into the interaction between IGF2BPs and ncRNAs in cancers DOI Creative Commons
Yiting Sun, Junjie Wu, Weimin Sun

et al.

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Dec. 28, 2024

Insulin-like growth factor II mRNA-binding proteins (IGF2BPs), a family of RNA-binding proteins, are pivotal in regulating RNA dynamics, encompassing processes such as localization, metabolism, stability, and translation through the formation ribonucleoprotein complexes. First identified 1999 for their affinity to insulin-like mRNA, IGF2BPs have been implicated promoting tumor malignancy behaviors, including proliferation, metastasis, maintenance stemness, which associated with unfavorable outcomes various cancers. Additionally, non-coding RNAs (ncRNAs), particularly long RNAs, circular microRNAs, play critical roles cancer progression intricate protein-RNA interactions. Recent studies, predominantly from 2018 onward, indicate that can recognize modulate ncRNAs via N6-methyladenosine (m6A) modifications, enriching regulatory landscape RNA–protein interactions context cancer. This review explores latest insights into interplay between ncRNAs, emphasizing potential influence on biology.

Language: Английский

Small molecule inhibitors targeting m6A regulators DOI Creative Commons

Guotai Feng,

Yongya Wu, Yuan Hu

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 6, 2024

As the most common form of epigenetic regulation by RNA, N

Language: Английский

Citations

12
IGF2BP2 Drives Cell Cycle Progression in Triple‐Negative Breast Cancer by Recruiting EIF4A1 to Promote the m6A‐Modified CDK6 Translation Initiation Process DOI Creative Commons
Tian Xia, Xinyuan Dai,

Ming‐Yi Sang

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 11(1)

Published: Nov. 20, 2023

Abstract IGF2BP2 is a new identified N6‐methyladenosine (m6A) reader and associated with poor prognosis in many tumors. However, its role related mechanism breast cancer, especially triple‐negative cancer (TNBC), remains unclear. In this study, it found that highly expressed TNBC due to the lower methylation level promoter region. Functional mechanical studies displayed could promote proliferation G1/S phase transition of cell cycle via directly regulating CDK6 an m6A‐dependent manner. Surprising, regulation protein levels by changes translation rate during initiation, rather than mRNA stability. Moreover, EIF4A1 be recruited output CDK6, providing evidence for regulatory between m6A translation. Downregulation enhance sensitivity abemaciclib, CDK4/6 inhibitor. To sum up, our study revealed facilitate recruiting also provided potential therapeutic target diagnosis treatment TNBC, as well strategy broadening drug indications inhibitors.

Language: Английский

Citations

16
WTAP‐Mediated m6A Modification of TRAIL‐DR4 Suppresses MH7A Cell Apoptosis DOI Open Access
Xiaoya Cui, Fengxia Xu,

Xue Pang

et al.

International Journal of Rheumatic Diseases, Journal Year: 2025, Volume and Issue: 28(1)

Published: Jan. 1, 2025

ABSTRACT Background N6‐methyladenosine (m6A) is one of the most conserved internal RNA modifications, which has been implicated in many biological processes, such as apoptosis and proliferation. Wilms tumor 1‐associating protein (WTAP), a key component m6A methylation, nuclear that associated with regulation proliferation apoptosis. Rheumatoid arthritis (RA), systemic, infiltrating autoimmune disease, characterized by synovial hyperplasia. However, little known about precise role WTAP RA. This study investigated WTAP‐mediated modification TNF‐related apoptosis‐inducing ligand death receptor 4 (TRAIL‐DR4) Method Methyltransferase overexpression plasmids small interfering RNAs were constructed transfected into MH7A cells. Immunofluorescence (IF) staining, quantitative reverse transcription polymerase chain reaction (RT‐qPCR), Western blot used to detect changes expression WTAP, B‐cell lymphoma 2 (BCL2) gene family, BCL2‐associated X (BAX) TRAIL‐DR4 expression, effects on cell viability, cycle, apoptosis, assessed counting kit‐8 (CCK‐8), flow cytometry, transmission electron microscopy (TEM). The was verified methylated immunoprecipitation‐qPCR (MeRIP‐qPCR) its stability an actinomycin D assay. Results Overexpression not only increased levels BCL2, decreased BAX TRAIL‐DR4, but also significantly inhibited promoted viability proliferation, while silencing led opposite trend. SRAMP online database predicted multiple potential methylation‐binding sites, fluorescence situ hybridization (FISH) combined IF showed mainly expressed both nucleus cytoplasm. MeRIP‐qPCR analysis experiments revealed could promote level decrease mRNA, subsequently inhibit Conclusion suggests suppresses discovery offers new focus avenue for clinical treatment RA, extending our understanding pathophysiology RA from standpoint alteration.

Language: Английский

Citations

0
Multifaceted roles of insulin‑like growth factor 2 mRNA binding protein 2 in human cancer (Review) DOI Creative Commons

Jianan Shen,

Youxiang Ding

Molecular Medicine Reports, Journal Year: 2025, Volume and Issue: 31(3)

Published: Jan. 24, 2025

Insulin‑like growth factor 2 mRNA binding protein (IGF2BP2) is an RNA that functions as N6‑methyladenosine reader. It regulates various biological processes in human cancers by affecting the stability and expression of target transcripts, including coding RNAs non‑coding (ncRNAs). Numerous studies have shown IGF2BP2 aberrantly increased types cancer plays multifaceted roles development progression cancers. In present review, clinical importance summarized its involvement regulation processes, proliferation, metastasis, chemoresistance, metabolism, tumor immunity, stemness cell death, discussed. The chemical compounds been developed inhibitors are also detailed. As ncRNAs now important potential therapeutic agents for treatment, microRNAs reported to directly inhibit described. summary, reviewing latest literature, study aimed highlight physiological cancer, with a focus on great inhibitor development. review may inspire new ideas future IGF2BP2, which serve specific cancer.

Language: Английский

Citations

0
IGF2BP2‐induced circRNF20 facilitates breast cancer cell proliferation via the HuR/CDCA4 axis DOI Creative Commons
Shenglong Wu, Xiaoli Hou, Fei Wang

et al.

The Kaohsiung Journal of Medical Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Abstract This study aimed to explore the mechanism of insulin‐like growth factor 2 mRNA‐binding protein (IGF2BP2) affecting proliferation breast cancer (BC) cells. The expression IGF2BP2, circRNA ring finger 20 (circRNF20), and cell division cycle‐associated 4 (CDCA4) in human BC cells normal epithelial was detected via RT‐qPCR or Western blotting. After IGF2BP2 altered, CCK‐8 assay, colony formation EdU staining were performed evaluate changes RNA immunoprecipitation (RIP) assay used analyze binding circRNF20 HuR, as well HuR CDCA4. pull‐down confirmed interaction between HuR. stability tested after treatment with actinomycin D. A nude mouse xenograft tumor model established validate effect vivo. circRNF20, CDCA4 highly expressed Silencing decreased ability Mechanistically, prevented degradation, thereby promoting increasing overexpression abolished inhibitory silencing on proliferation. In conclusion, prevents its thus facilitating HuR/CDCA4 axis.

Language: Английский

Citations

0
IMPlications of IMP2 in RNA Biology and Disease DOI Open Access

J. Das,

Ottavia Busia-Bourdain,

Khizr M. Khan

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2415 - 2415

Published: March 7, 2025

Insulin-like growth factor 2 mRNA-binding protein (IMP2) is an RNA-binding that positively regulates m6A-modified RNAs involved in critical cellular processes such as metabolism, oncogenesis, and immune function. Here, we elucidate facets of IMP2 biology, including several mechanisms action on RNA, factors regulate expression, its relevant biological target RNAs, role normal development disease, potential a therapeutic target. multi-level regulator influencing pathways linked to diabetes, obesity, adipose Through genomic amplification transcriptional overexpression cancer cells, can drive the initiation progression multiple types, high expression associated with decreased overall survival patients cancer. influences function, inflammation, macrophage polarization, tumor evasion. has emerged promising target, particularly for cancers metabolic diseases.

Language: Английский

Citations

0
Replication factor C4, which is regulated by insulin-like growth factor 2 mRNA binding protein 2, enhances the radioresistance of breast cancer by promoting the stemness of tumor cells DOI
Xiaoyu Zhu,

Pi-Song Li,

Hui Qu

et al.

Human Cell, Journal Year: 2025, Volume and Issue: 38(3)

Published: March 7, 2025

Language: Английский

Citations

0
Clinical data investigation identifies MARK3 as an oncogenic driver in castration-resistant prostate cancer DOI
Rajnikant Raut, Devesh Srivastava, Vinayak Nayak

et al.

Biochemistry and Biophysics Reports, Journal Year: 2025, Volume and Issue: 42, P. 102003 - 102003

Published: April 8, 2025

Language: Английский

Citations

0
IGF2BP2: an m6A reader that affects cellular function and disease progression DOI Creative Commons
Siyi Liu,

Shan Liao,

Junyu He

et al.

Cellular & Molecular Biology Letters, Journal Year: 2025, Volume and Issue: 30(1)

Published: April 9, 2025

Abstract Insulin-like growth factor 2 messenger RNA (mRNA)-binding protein (IGF2BP2) is a widely studied N 6 -methyladenosine (m A) modification reader, primarily functioning to recognize and bind m A sites on the mRNA of downstream target genes, thereby enhancing their stability. Previous studies have suggested that IGF2BP2-m plays an essential role in cellular functions progression various diseases. In this review, we focus summarizing molecular mechanisms by which IGF2BP2 enhances stability genes through modification, regulating cell ferroptosis, epithelial–mesenchymal transition (EMT), stemness, angiogenesis, inflammatory responses, lipid metabolism, ultimately affecting disease progression. Additionally, update related research progress IGF2BP2. This article aims elucidate effects EMT, providing new perspective for comprehensive understanding relationship between such as ferroptosis well potential targeted therapy tumors other

Language: Английский

Citations

0
Integrative analysis of m6A-SNPs and single-cell RNA sequencing reveals key drivers of endocrine combined with CDK4/6 inhibitor therapy resistance in ER+ breast cancer DOI Creative Commons

Ruijie Ming,

Han Zhang, Huan Wu

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 15, 2025

Background Endocrine therapy combined with CDK4/6 inhibitors remains a standard treatment for ER+ breast cancer, yet resistance is prevalent challenge. This study explores the role of N6-methyladenosine (m6A) modifications, influenced by m6A-SNPs, in shaping resistance, utilizing single-cell RNA sequencing to delineate underlying molecular mechanisms. Methods We integrated genome-wide association data transcriptomic profiles from cancer patients, focusing on differences between resistant and sensitive responses inhibitors. m6A-SNPs were identified analyzed their impact gene expression interactions RNA-binding proteins, particular focus roles within key cellular pathways. Results The crucial associated resistance. Notably, changes FILIP1L TOM1L1, related these SNPs, mapped using pseudotime trajectory analysis, which traced evolution states. TOM1L1 exhibited dynamic along trajectory, correlating significant shifts cell fate decisions. These findings underscore potential as mediators development particularly through involvement PI3K-Akt Wnt signaling pathways, critical progression drug Conclusion Our emphasize importance influencing cancer. regulation developmental tumor cells sensitivity provides insights into complexity results pave way developing targeted therapies that modify m6A-driven offering new strategies counteract improve patient outcomes.

Language: Английский

Citations

0