2. Academic Validation
  3. YTHDF2 promotes anaplastic thyroid cancer progression by activating the DDIT4/AKT/mTOR signaling pathway

YTHDF2 promotes anaplastic thyroid cancer progression by activating the DDIT4/AKT/mTOR signaling pathway

  • Biol Direct. 2024 Nov 26;19(1):122. doi: 10.1186/s13062-024-00566-y.
Bao Dai # 1,  Lei Xu # 1 2,  Shikuo Rong # 3,  Muye Song 4,  Ziteng Lan 1,  Weijian Chen 1,  Lingyun Zhang 1,  Yongchen Liu 1,  Linhe Wang 1,  Jinghua Li 5,  Jian Chen 6,  Zeyu Wu 7
Affiliations

Affiliations

  • 1 Department of Thyroid and Hernia Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510080, China.
  • 2 Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • 3 Division of Thyroid surgery, Department of General Surgery, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University ), Shenzhen, Guangdong, China.
  • 4 Department of Anesthesiology, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510080, China.
  • 5 Department of Laboratory, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences, Southern Medical University, 106 Zhongshan 2nd Road, Guangzhou, Guangdong, 510080, China. ljhde@163.com.
  • 6 Department of Thyroid and Hernia Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510080, China. chenj@gdph.org.cn.
  • 7 Department of Thyroid and Hernia Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510080, China. wuzeyu@gdph.org.cn.
  • # Contributed equally.
PMID: 39593172 DOI: 10.1186/s13062-024-00566-y
Abstract

Background: RNA methylation, an important reversible post-transcriptional modification in eukaryotes, has emerged as a prevalent epigenetic alteration. However, the role of the m6A reader YTH domain family 2 (YTHDF2) has not been reported in anaplastic thyroid Cancer (ATC) and its biological mechanism is unclear.

Methods: The relationship between YTHDF2 expression and ATC was determined using data sets and tissue samples. A range of analytical techniques were employed to investigate the regulatory mechanism of YTHDF2 in ATC, including bioinformatics analysis, m6A dot-blot analysis, methylated RNA immunoprecipitation Sequencing (MeRIP-seq), RNA immunoprecipitation (RIP) assays, RNA Sequencing, RNA stability assays and dual luciferase reporter gene assays. In vitro and in vivo assays were also conducted to determine the contribution of YTHDF2 to ATC development.

Results: YTHDF2 expression was significantly increased in ATC. The comprehensive in vitro and in vivo experiments demonstrated that YTHDF2 knockdown significantly attenuated ATC proliferation, invasion, migration, and Apoptosis promotion, whereas YTHDF2 overexpression yielded the opposite trend. Mechanistically, RNA-seq, MeRIP-seq and RIP-seq analysis, and Molecular Biology experiments demonstrated that YTHDF2 accelerated the degradation of DNA damage-inducible transcript 4 or regulated in DNA damage and development 1 (DDIT4, or REDD1) mRNA in an m6A-dependent manner, which in turn activated the Akt/mTOR signaling pathway and induced activation of epithelial-mesenchymal transition (EMT), thereby promoting ATC tumor progression.

Conclusions: This study is the first to demonstrate that elevated YTHDF2 expression levels suppress DDIT4 expression in an m6A-dependent manner and activate the Akt/mTOR signaling pathway, thereby promoting ATC progression. YTHDF2 plays a pivotal role in ATC progression, and it may serve as a promising therapeutic target in the future.

Keywords

AKT; Anaplastic thyroid cancer; YTHDF2; m6A; mTOR.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z