2. Academic Validation
  3. Glioblastoma upregulates SUMOylation of hnRNP A2/B1 to eliminate the tumor suppressor miR-204-3p, accelerating angiogenesis under hypoxia

Glioblastoma upregulates SUMOylation of hnRNP A2/B1 to eliminate the tumor suppressor miR-204-3p, accelerating angiogenesis under hypoxia

  • Cell Death Dis. 2023 Feb 21;14(2):147. doi: 10.1038/s41419-023-05663-w.
Qindong Guo 1 2,  Yang Fan 1 2,  Qingtong Wang 1 2,  Boyan Li 1 2,  Wei Qiu 1 2,  Yanhua Qi 1 2,  Ziwen Pan 1 2,  Shouji Zhang 1 2,  Shulin Zhao 1 2,  Kehui Yang 3,  Hao Xu 2 4,  Ming Li 2 5,  Zijie Gao 1 2,  Jianye Xu 1 2,  Huizhi Wang 1 2,  Shaobo Wang 1 2,  Qilin Tang 1 2,  Jiawei Qiu 1 2,  Xing Guo 1 2,  Lin Deng 1 2,  Ping Zhang 1 2,  Rongrong Zhao 1 2,  Hao Xue 1 2,  Chengwei Wang 6,  Gang Li 7 8
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, Shandong, China.
  • 2 Shandong Key Laboratory of Brain Function Remodeling, Jinan, Shandong, China.
  • 3 Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China.
  • 4 Department of Neurosurgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
  • 5 Department of Neurosurgery, The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, China.
  • 6 Department of Neurosurgery, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China. wangchengwei@sdu.edu.cn.
  • 7 Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, Shandong, China. dr.ligang@sdu.edu.cn.
  • 8 Shandong Key Laboratory of Brain Function Remodeling, Jinan, Shandong, China. dr.ligang@sdu.edu.cn.
PMID: 36810326 DOI: 10.1038/s41419-023-05663-w
Abstract

Glioma is the most common malignant tumor of the central nervous system in adults. The tumor microenvironment (TME) is related to poor prognosis in glioma patients. Glioma cells could sort miRNA into exosomes to modify TME. And hypoxia played an important role in this sorting process, but the mechanism is not clear yet. Our study was to find miRNAs sorted into glioma exosomes and reveal the sorting process. Sequencing analysis of glioma patients cerebrospinal fluid (CSF) and tissue showed that miR-204-3p tends to be sorted into exosomes. miR-204-3p suppressed glioma proliferation through the CACNA1C/MAPK pathway. hnRNP A2/B1 can accelerate exosome sorting of miR-204-3p by binding a specific sequence. Hypoxia plays an important role in exosome sorting of miR-204-3p. Hypoxia can upregulate miR-204-3p by upregulating the translation factor SOX9. Hypoxia promotes the transfer of hnRNP A2/B1 to the cytoplasm by upregulating SUMOylation of hnRNP A2/B1 to eliminate miR-204-3p. Exosomal miR-204-3p promoted tube formation of vascular endothelial cells through the ATXN1/STAT3 pathway. The SUMOylation inhibitor TAK-981 can inhibit the exosome-sorting process of miR-204-3p to inhibit tumor growth and angiogenesis. This study revealed that glioma cells can eliminate the suppressor miR-204-3p to accelerate angiogenesis under hypoxia by upregulating SUMOylation. The SUMOylation inhibitor TAK-981 could be a potential drug for glioma. This study revealed that glioma cells can eliminate the suppressor miR-204-3p to accelerate angiogenesis under hypoxia by upregulating SUMOylation. The SUMOylation inhibitor TAK-981 could be a potential drug for glioma.

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