2. Academic Validation
  3. ALKBH5 enhances lipid metabolism reprogramming by increasing stability of FABP5 to promote pancreatic neuroendocrine neoplasms progression in an m6A-IGF2BP2-dependent manner

ALKBH5 enhances lipid metabolism reprogramming by increasing stability of FABP5 to promote pancreatic neuroendocrine neoplasms progression in an m6A-IGF2BP2-dependent manner

  • J Transl Med. 2023 Oct 19;21(1):741. doi: 10.1186/s12967-023-04578-6.
Jinhao Chen # 1 2,  Mujie Ye # 1 2,  Jianan Bai # 1 2,  Zhihui Gong # 3,  Lijun Yan 1 2,  Danyang Gu 1 2,  Chunhua Hu 1 2,  Feiyu Lu 1 2,  Ping Yu 1 2,  Lin Xu 1 2,  Yan Wang 4 5 6,  Ye Tian 7 8,  Qiyun Tang 9 10
Affiliations

Affiliations

  • 1 Department of Geriatric Gastroenterology, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Institute of Neuroendocrine Tumor, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China.
  • 2 Digestive Endoscopy, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 3 Department of Gastroenterology, The Friendship Hospital of Ili Kazakh Autonomous Prefecture, Ili & Jiangsu Joint Institute of Health, Yining, 835000, Ili State, China.
  • 4 Department of Geriatric Gastroenterology, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Institute of Neuroendocrine Tumor, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China. wy_797@126.com.
  • 5 Digestive Endoscopy, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. wy_797@126.com.
  • 6 Department of Gastroenterology, The Friendship Hospital of Ili Kazakh Autonomous Prefecture, Ili & Jiangsu Joint Institute of Health, Yining, 835000, Ili State, China. wy_797@126.com.
  • 7 Department of Geriatric Gastroenterology, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Institute of Neuroendocrine Tumor, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China. tianye6626@126.com.
  • 8 Digestive Endoscopy, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. tianye6626@126.com.
  • 9 Department of Geriatric Gastroenterology, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Institute of Neuroendocrine Tumor, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China. tqy831@163.com.
  • 10 Digestive Endoscopy, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. tqy831@163.com.
  • # Contributed equally.
PMID: 37858219 DOI: 10.1186/s12967-023-04578-6
Abstract

The process of post-transcriptional regulation has been recognized to be significantly impacted by the presence of N6-methyladenosine (m6A) modification. As an m6A demethylase, ALKBH5 has been shown to contribute to the progression of different cancers by increasing expression of several oncogenes. Hence, a better understanding of the key targets of ALKBH5 in Cancer cells could potentially lead to the development of new therapeutic targets. However, the specific role of ALKBH5 in pancreatic neuroendocrine neoplasms (pNENs) remains largely unknown. Here, we demonstrated that ALKBH5 was up-regulated in pNENs and played a critical role in tumor growth and lipid metabolism. Mechanistically, ALKBH5 over-expression was found to increase the expression of FABP5 in an m6A-IGF2BP2 dependent manner, leading to disorders in lipid metabolism. Additionally, ALKBH5 was found to activate PI3K/Akt/mTOR signaling pathway, resulting in enhanced lipid metabolism and proliferation abilities. In conclusion, our study uncovers the ALKBH5/IGF2BP2/FABP5/mTOR axis as a mechanism for aberrant m6A modification in lipid metabolism and highlights a new molecular basis for the development of therapeutic strategies for pNENs treatment.

Keywords

ALKBH5; FABP5; Lipid metabolism; N6-Methyladenosine (m6A); Pancreatic neuroendocrine neoplasms.

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