2. Academic Validation
  3. Inhibition of KIAA1429/HK1 axis enhances the sensitivity of liver cancer cells to sorafenib by regulating the Warburg effect

Inhibition of KIAA1429/HK1 axis enhances the sensitivity of liver cancer cells to sorafenib by regulating the Warburg effect

  • Biochem Pharmacol. 2024 Jul 10:116419. doi: 10.1016/j.bcp.2024.116419.
Dong Liu 1,  Meihua Shan 1,  Rong Zeng 2,  Meng He 3,  Xufang Dai 4,  Lu Lu 1,  Mingzhen Yang 1,  Haiyan He 3,  Yang Zhang 1,  Li Xiang 1,  An Chen 1,  Liangbo Sun 5,  Fengtian He 6,  Jiqin Lian 7
Affiliations

Affiliations

  • 1 Department of Clinical Biochemistry, Army Medical University, Chongqing 400038, China.
  • 2 Department of Medicinal Chemistry, Army Medical University, Chongqing 400038, China.
  • 3 Department of Biochemistry and Molecular Biology, Army Medical University, Chongqing 400038, China.
  • 4 College of Education Science, Chongqing Normal University, Chongqing 400047, China.
  • 5 Department of Clinical Biochemistry, Army Medical University, Chongqing 400038, China. Electronic address: 807125461@qq.com.
  • 6 Department of Biochemistry and Molecular Biology, Army Medical University, Chongqing 400038, China. Electronic address: hefengtian66@aliyun.com.
  • 7 Department of Clinical Biochemistry, Army Medical University, Chongqing 400038, China. Electronic address: lianjiqin@tmmu.edu.cn.
PMID: 38996929 DOI: 10.1016/j.bcp.2024.116419
Abstract

N6-methyladenosine (m6A) serves as the most abundant posttranscription modification. However, the role of m6A in tumorigenesis and chemotherapeutic drugs sensitivity remains largely unclear. Present research focuses on the potential function of the m6A writer KIAA1429 in tumor development and sorafenib sensitivity in liver Cancer. We found that the level of KIAA1429 was significantly elevated in liver Cancer tissues and cells and was closely associated with poorer prognosis. Functionally, KIAA1429 promoted the proliferation and Warburg effect of liver Cancer cells in vitro and in vivo. RNA-seq and MeRIP-seq analysis revealed the glycolysis was one of the most affected pathways by KIAA1429, and m6A-modified HK1 was the most likely targeted gene to regulate the Warburg effect. KIAA1429 depletion decreased Warburg effect and increased sorafenib sensitivity in liver Cancer. Mechanistically, KIAA1429 could affect the m6A level of HK1 mRNA through directly binding with it. Moreover, KIAA1429 cooperated with the m6A reader HuR to enhance HK1 mRNA stability, thereby upregulating its expression. These findings demonstrated that KIAA1429/HK1 axis decreases the sensitivity of liver Cancer cells to sorafenib by regulating the Warburg effect, which may provide a novel therapeutic target for liver Cancer treatment.

Keywords

HK1; KIAA1429; Liver cancer; Sorafenib; Warburg effect; m6A.

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