Knockdown of BCL6 Inhibited Malignant Phenotype and Enhanced Sensitivity of Glioblastoma Cells to TMZ through AKT Pathway.
Knockdown of BCL6 Inhibited Malignant Phenotype and Enhanced Sensitivity of Glioblastoma Cells to TMZ through AKT Pathway.
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BCL6 的敲低通过 AKT 途径抑制恶性表型并增强胶质母细胞瘤细胞对 TMZ 的敏感性
DOI：
10.1155/2018/6953506
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发表时间：
2018
影响因子：
--
通讯作者：
Zhang B
中科院分区：
文献类型：
--
作者：
Song W;Wang Z;Kan P;Ma Z;Wang Y;Wu Q;Yao X;Zhang B
研究背景BCL 6是人类B细胞淋巴瘤的一个重要原癌基因，在多种恶性肿瘤的发生、发展过程中起重要作用。本研究旨在探讨BCL 6在胶质瘤中的表达及其生物学效应。方法采用RT-PCR和Western blot方法检测胶质母细胞瘤组织和胶质母细胞瘤细胞系中BCL 6 mRNA和蛋白的表达。用BCL 6 shRNA在两个胶质母细胞瘤细胞系（U87和U251）中敲低BCL 6的表达。采用CCK-8法、集落形成法、流式细胞术、Transwell法和伤口愈合法检测胶质母细胞瘤细胞的恶性表型变化。结果BCL 6在胶质瘤组织和胶质母细胞瘤细胞系中的表达均高于正常组织。BCL 6表达的敲低降低了胶质母细胞瘤细胞的增殖、迁移和侵袭。此外，BCL 6的敲低改变了与胶质母细胞瘤细胞恶性行为相关的蛋白质的表达。抑制BCL 6可增加U87和U251对替莫唑胺的化疗敏感性。BCL 6水平的下调抑制了BCL 2、细胞周期蛋白D1、MMP 2和MMP 9蛋白以及两种经典信号通路蛋白p-AKT和p-ERK的表达。同时，BAX和p21蛋白水平随着BCL 6的敲低而沿着上调。结论BCL 6可能是一种肿瘤癌基因，通过影响AKT和MAPK信号通路参与胶质瘤的发生发展。
Background BCL6 was a critical prooncogene of human B-cell lymphomas which promoted tumor progress and contributed to malignant behavior in several kinds of cancers. This study was to detect the expression of BCL6 and its biological effect on glioma. Methods RT-PCR and Western blot were used to detect the expression of BCL6 mRNA and protein in tissues and glioblastoma cell lines. The expression of BCL6 was knockdown in two glioblastoma cell lines (U87 and U251) using BCL6 shRNA. The CCK8, colony-formation, flow cytometry, Transwell, and wound-healing assays were used to evaluate the malignant phenotypic change of glioblastoma cells. Results The expression of BCL6 was higher in glioma tissues and glioblastoma cell lines than normal tissues. Knockdown of BCL6 expression reduced the proliferation, migration, and invasion of glioblastoma cells. Moreover, knockdown of BCL6 changed expression of proteins related to malignant behaviors of glioblastoma cells. The suppression of BCL6 could increase chemosensitivity of U87 and U251 to temozolomide. Downregulation of BCL6 levels suppressed the expression of BCL2, cyclin D1, MMP2, and MMP9 proteins as well as two classic signaling pathway proteins p-AKT and p-ERK. Simultaneously, BAX and p21 protein levels were upregulated along with knockdown of BCL6. Conclusions Our results indicated that BCL6 may be a tumor oncogene involved in the progression of glioma via affecting AKT and MAPK signaling pathways.
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B细胞淋巴瘤6蛋白刺激人乳腺癌细胞的致癌性
影响因子：
3.8
作者：
Wu Q;Liu X;Yan H;He YH;Ye S;Cheng XW;Zhu GL;Wu WY;Wang XN;Kong XJ;Xu XC;Lobie PE;Zhu T;Wu ZS
通讯作者：
Wu ZS
影响因子：
11.2
作者：
Tran TH;Utama FE;Lin J;Yang N;Sjolund AB;Ryder A;Johnson KJ;Neilson LM;Liu C;Brill KL;Rosenberg AL;Witkiewicz AK;Rui H
通讯作者：
Rui H
影响因子：
3.9
作者：
Minniti, G.;De Sanctis, V.;Enrici, R. Maurizi
通讯作者：
Enrici, R. Maurizi
影响因子：
20.3
作者：
Basso, Katia;Saito, Masumichi;Dalla-Favera, Riccardo
通讯作者：
Dalla-Favera, Riccardo
影响因子：
10.5
作者：
Shvarts, A;Brummelkamp, TR;Bernards, R
通讯作者：
Bernards, R