2. Academic Validation
  3. Overexpression of Annexin A2 promotes proliferation by forming a Glypican 1/c-Myc positive feedback loop: prognostic significance in human glioma

Overexpression of Annexin A2 promotes proliferation by forming a Glypican 1/c-Myc positive feedback loop: prognostic significance in human glioma

  • Cell Death Dis. 2021 Mar 12;12(3):261. doi: 10.1038/s41419-021-03547-5.
Xin Li 1 2,  Shengdan Nie 3,  Ziyang Lv 2,  Lingran Ma 2,  Yuxi Song 2,  Zhongxu Hu 1,  Xin Hu 2,  Zhiqiang Liu 1,  Gaoya Zhou 4,  Zhijie Dai 5,  Tao Song 6,  Jiajia Liu 7,  Shan Wang 8
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Xiang-Ya Hospital, Central South University, Changsha, China.
  • 2 Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, China.
  • 3 Institute of Clinical Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.
  • 4 Department of Neurology, Brain Hospital of Hunan Province, Changsha, China.
  • 5 Department of Institute of Metabolism and Endocrinology, Second Xiang-Ya Hospital, Central South University, Changsha, China.
  • 6 Department of Neurosurgery, Xiang-Ya Hospital, Central South University, Changsha, China. songtaocsuws@163.com.
  • 7 Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, China. liujj0903@163.net.
  • 8 Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, China. wangshancsu0717@163.com.
PMID: 33712571 DOI: 10.1038/s41419-021-03547-5
Abstract

In order to set up a reliable prediction system for the tumor grade and prognosis in glioma patients, we clarify the complicated crosstalk of Annexin A2 (ANXA2) with Glypican 1 (GPC1) and demonstrate whether combined indexes of ANXA2 and GPC1 could improve the prognostic evaluation for glioma patients. We found that ANXA2-induced glioma cell proliferation in a c-Myc-dependent manner. ANXA2 increased the expression of GPC1 via c-Myc and the upregulated GPC1 further promoted the c-Myc level, forming a positive feedback loop, which eventually led to enhanced proliferation of glioma cells. Both mRNA and protein levels of ANXA2 were upregulated in glioma tissues and coincided with the overexpression of GPC1. Besides, we utilized tissue microarrays (TMAs) and immunohistochemistry to demonstrate that glioma patients with both high expression of ANXA2 and GPC1 tended to have higher rate of tumor recurrence and shorter overall survival (OS). In conclusion, the overexpression of ANXA2 promotes proliferation of glioma cells by forming a GPC1/c-Myc positive feedback loop, and ANXA2 together with its downstream target GPC1 could be a potential "combination biomarker" for predicting prognosis of glioma patients.

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