Glioma is the most frequent and aggressive adult brain tumor with maximum mortality. However, the gene alteration and mechanism underlying malignant transformation of glioma remain largely unknown. We aimed to find key factors regulating tumor progression and malignant transformation of glioma. Here we compared the gene expression profiles of 693 glioma patients by HGG vs. LGG model, and identified a key factor CCNB2 for malignant transformation in glioma. CCNB2 induced a senescence-associated secretory phenotype (SASP) of glioma cells, and the malignant progression, such as invasion and excessive proliferation was mediated by secreting SASP cytokines, Cathepsin B and PGE2. These findings demonstrated a previously undiscovered link between senescence, CCNB2/SASP/Cathepsin B & PGE2 axis and malignant transformation in glioma. This might provide novel insights on developing new therapeutic regimens for abrogating aggressiveness of glioma.

中文翻译：

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CCNB2/SASP/组织蛋白酶 B 和 PGE2 轴诱导细胞衰老介导的恶性转化

胶质瘤是最常见和侵袭性最高的成人脑肿瘤，死亡率最高。然而，神经胶质瘤恶性转化的基因改变和机制仍然很大程度上未知。我们旨在寻找调节胶质瘤肿瘤进展和恶性转化的关键因素。在这里，我们通过 HGG 与 LGG 模型比较了 693 名胶质瘤患者的基因表达谱，并确定了胶质瘤恶性转化的关键因素 CCNB2。CCNB2诱导胶质瘤细胞衰老相关分泌表型（SASP），通过分泌SASP细胞因子、组织蛋白酶B和PGE2介导恶性进展，如侵袭和过度增殖。这些发现证明了衰老、CCNB2/SASP/组织蛋白酶 B 和 PGE2 轴与胶质瘤恶性转化之间以前未被发现的联系。