2. Academic Validation
  3. Generation of B7-H3 isoform regulated by ANXA2/NSUN2/YBX1 axis in human glioma

Generation of B7-H3 isoform regulated by ANXA2/NSUN2/YBX1 axis in human glioma

  • J Cell Mol Med. 2024 Jul;28(14):e18575. doi: 10.1111/jcmm.18575.
Yifen Shen 1,  Chunfang Ma 2,  Xiangxiang Li 2,  Xiaosong Li 3,  Yuxiang Wu 4,  Tao Yang 5,  Yanping Hu 6,  Chao Liu 1,  Hao Shen 2,  Pin Guo 7,  Yihang Shen 1
Affiliations

Affiliations

  • 1 Central Laboratory, Suzhou Bay Clinical College, Xuzhou Medical University, Suzhou Ninth People's Hospital, Suzhou, Jiangsu, China.
  • 2 Clinical Laboratory, Suzhou Ninth People's Hospital, Suzhou, Jiangsu, China.
  • 3 Department of Anorectal Surgery, Suzhou Ninth People's Hospital, Suzhou, Jiangsu, China.
  • 4 Department of Pathology, Suzhou Ninth People's Hospital, Suzhou, Jiangsu, China.
  • 5 Department of Medical Cosmetology, Suzhou Ninth People's Hospital, Soochow University, Suzhou, Jiangsu, China.
  • 6 Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China.
  • 7 Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
PMID: 39048916 DOI: 10.1111/jcmm.18575
Abstract

In recent years, in the development of emerging immunotherapy, B7-H3 is also termed as CD276 and has become a novel chimeric antigen receptor (CAR)-T target against glioma and Other tumours, and aroused extensive attention. However, B7-H3 has three isoforms (2, 3 and 4Ig) with the controversial expression and elusive function in tumour especially glioma. The current study mainly focuses on the regulatory factors and related mechanisms of generation of different B7-H3 isoforms. First, we have determined that 2Ig is dominant in glioma with high malignancy, and 4Ig is widely expressed, whereas 3Ig shows negative expression in all glioma. Next, we have further found that RNA binding protein annexin A2 (AnxA2) is essential for B7-H3 isoform maintenance, but fail to determine the choice of 4Ig or 2Ig. RNA methyltransferase NOP2/Sun RNA methyltransferase 2 (NSUN2) and 5-methylcytosine reader Y-box binding protein 1 (YBX1) facilitate the production of 2Ig. Our findings have uncovered a series of factors (AnxA2/NSUN2/YBX1) that can determine the alternative generation of different isoforms of B7-H3 in glioma. Our result aims to help peers gain a clearer understanding of the expression and regulatory mechanisms of B7H3 in tumour patients, and to provide better strategies for designing B7H3 as a target in immunotherapy.

Keywords

2Ig isoform; ANXA2; B7‐H3; NSUN2; RNA methylation; YBX1.

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