Nuclear factor-kappa B1 inhibits early apoptosis of glioma cells by promoting the expression of Bcl-2

Abstract

Glioma is one of the most common types of adult primary brain tumors, and the underlying molecular mechanisms still remain unclear. Nuclear factor-kappa B1 (NF-κB1) is involved in a variety of malignancies and is widely expressed in malignant tumors. However, the expression of NF-κB1 in different grades of glioma, the correlation between NF-κB1 and Bcl-2 expressions in gliomas, and the research between NF-κB1 and early apoptosis of glioma cells have not been reported so far. In this study, the expression level of NF-κB1 in 31 human glioma tissues and six nonneoplastic brain tissues was determined using quantitative real-time polymerase chain reaction. Results showed that the expression of NF-κB1 in human glioma tissues and glioma cell lines, SHG44 and U87, was significantly higher compared to noncancerous brain tissues and that the expression increased with increasing degrees of tumor malignancy. Similar results were demonstrated with the expression of Bcl-2 in the same human glioma specimens. Flow cytometry results showed that inhibition of NF-κB1 expression significantly promoted apoptosis of SHG44 and U87 in human glioma cells. Western blot analysis further confirmed decreased expression of Bcl-2 protein after inhibition of NF-κB1 protein expression. Taken together, NF-κB1 overexpression inhibits early apoptosis of glioma cells and high expression of NF-κB1 promotes the expression of antiapoptotic gene Bcl-2. Therefore, our study results provide a theoretical basis for antiapoptotic mechanism of tumor cells in association with NF-κB1.

MicroRNA-153-3p enhances cell radiosensitivity by targeting BCL2 in human glioma

“…BCL2 has a unique role as master negative regulator of apoptosis in mammalian cells [ 16 ]. The abnormal amplification of BCL2 protein has been reported in a wide range of malignancies, including leukemia, colorectal cancer, and lymphomas, and nervous system cancers [ 17 – 19 ]. Many independent studies, for example by ectopic expression or knockdown have demonstrated that upregulation of BCL2 abrogates apoptotic responses to radiotherapy, while downregulation of BCL2 leads to elevated sensitivity to IR [ 20 ].…”

Sulphur doped carbon dots enhance photodynamic therapy via PI3K/Akt signalling pathway

“…Upon activation by PI3K, Akt is phosphorylated and then inhibits the function of the pro‐apoptotic Bcl‐2 family members, resulting in cell death inhibition 13,40 . NF‐κB is a transcription factor and also a downstream effector of the Akt pathway, 41 and it could inhibit early apoptosis of glioma cells by promoting the expression of Bcl‐2 34,42 . The variation of these signalling pathways resulted in imbalance of the Bcl‐2 family proteins, including decreased anti‐apoptotic proteins (such as Bcl‐2) and increased pro‐apoptotic proteins (such as Bax) 43,44 .…”

Analysis of microarray data for identification of key microRNA signatures in glioblastoma multiforme

“…BMI1, NOTCH1, HRAS, CCND1, MCL1, BCL2, VEGFA, MET and NFKB1 were enriched in ‘MicroRNAs in cancer pathway’. Other significantly enriched pathways included, renal cell carcinoma, prostate cancer and hepatitis B. Amongst the target genes enriched in different pathways, NFKB1 is found to be associated with many types of human cancers including GBM (55,56) and is known to be elevated in glioma cells (57). Overexpression of NFKB1 inhibited the apoptosis of glioma cells by inducing the BCL2 expression.…”