Knockdown of BCL6 Inhibited Malignant Phenotype and Enhanced Sensitivity of Glioblastoma Cells to TMZ through AKT Pathway

Abstract

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.

Amplification-driven BCL6-suppressed cytostasis is mediated by transrepression of FOXO3 and post-translational modifications of FOXO3 in urinary bladder urothelial carcinoma

“…It is well known that AKT1 phosphorylate T32, S253 and S315 whilst MAPK1/3 phosphorylates S284, S294, S325, S425 and T487 residues on the FOXO3 protein (reviewed in 37). In glioblastoma cells, knockdown of the BCL6 gene inhibited malignant phenotype and enhanced sensitivity to temozolomide through inhibition of the AKT pathway 38. We applied EGFR, MAP2K1/2 and PI3K/AKT inhibitors in BCL6 -overexpressed, transfection of pFOXO3(TM)-HaloTag in stable BCL6 -knockdown cells, constitutively active AKT1 expression in BCL6 -knockdown UBUC-derived cells in conjunction with cell proliferation and immunblot assays to provide solid evidence that BCL6 promotes cell proliferation may also through modulations of the EGFR-MAP2K1/2-FOXO3 and/or PI3K-AKT-FOXO3 signaling pathways at the post-translational level in two cell lines with genetic heterogeneity.…”

In vitro evaluation of anticancer effects of different probiotic strains on HCT‐116 cell line

“…It has been suggested that knockdown of BCL6 expression in glioblastoma cells reduced the proliferation, migration, and invasion (Song et al . 2018). Moreover, these cells are sensitive to temozolomide, a chemotherapeutic drug.…”

B-cell Lymphoma 6 (BCL6): From Master Regulator of Humoral Immunity to Oncogenic Driver in Pediatric Cancers

“…More recent studies showed that molecular inhibition of BCL6 expression in glioblastoma cell lines decreased expression of BCL2, and Cyclin D1 (CCND1), and proteins influencing the diffuse migratory and invasive growth features of these tumors influenced by matrix metalloproteinases-MMP2 and MMP9. Commensurate, BCL6 knockdown increased the expression of proapoptotic protein BAX and CDKN1A to potentiate p53 activity in response to radiation and decreased Extracellular signal-regulated kinase (ERK) signaling (9,75). The Tyrosine-protein kinase receptor (AXL) is a transcriptional target of BCL6 and responsible for the decreased ERK activity following BCL6 or AXL inhibition in glioblastoma.…”