BCLAF1 induces cisplatin resistance in lung cancer cells

Abstract

Treatment for non-small cell lung cancer (NSCLC) remains challenging due to frequent recurrence and the development of resistance to platinum-based chemotherapy. The mechanism underlying NSCLC chemoresistance remains unclear. The present study aimed to investigate the mechanism of cisplatin resistance in NSCLC cells and it found that the expression of Bcl-2-associated transcription factor 1 (BCLAF1) was higher in the A549 cell line with cisplatin resistance (A549/DDP) by western blotting and reverse-transcription quantitative PCR, suggesting that elevated BCLAF1 expression is associated with acquired cisplatin resistance in A549 cells. BCLAF1 was found to promote DNA damage repair in A549/DDP cells by regulating γH2A histone family member X foci formation by immunofluorescence and western blotting. BCLAF1 was also demonstrated to regulate ubiquitin-specific peptidase 22 mRNA expression in A549/DDP cells, in addition to regulating G 1 phase arrest by targeting p21 expression. Taken together, these findings suggest that BCLAF1 mediates cisplatin resistance by regulating the repair of DNA damage and p21-mediated G 1 phase arrest.

Bcl-2-associated transcription factor 1 Ser290 phosphorylation mediates DNA damage response and regulates radiosensitivity in gastric cancer

“…Notably, Bcl-2-associated transcription factor 1 (BCLAF1), a death-promoting transcriptional repressor highly expressed in a variety types of cancer [ 14 – 17 ], is shown to be phosphorylated at multiple positions. BCLAF1 is involved in a wide range of biological processes including apoptosis, transcriptional regulation and DNA damage repair [ 18 – 21 ]. The BCLAF1 protein contains homologies to the basic zipper and Myb DNA-binding domain and can bind to DNA [ 22 ].…”

“…BCLAF1 promotes the transcription of TP53 gene by interaction with PKCδ in response to DNA damage and interacts with γ-H2AX upon ionizing radiation (IR) [ 24 ]. BCLAF1 also induces cisplatin resistance in lung cancer cells by regulating DNA damage repair [ 18 ]. However, it remained to be determined how BCLAF1 phosphorylation regulates DNA damage response.…”

N-Glycoproteomics Study of Putative N-Glycoprotein Biomarkers of Drug Resistance in MCF-7/ADR Cells

“…Bcl-2-associated transcription factor 1 (BCLAF1) showed higher expression level in cisplatin resistance non-small cell lung cancer A549 (A549/DDP) cell line than in A549 cell line as characterized by western blotting and RT-qPCR (Jiang et al 2020). Furthermore, BCLAF1 facilitated DNA damage repair by mediating the forming process of γH2A histone family member X foci formation via immunofluorescence and western blot (Jiang et al 2020). Glycerol-3-phosphate acyltransferase (GPAT) is responsible for the catalysis of de novo synthesis of glycerolipids in cells (Pellon-Maison et al 2014).…”

“…Bcl-2 functioned as an antiapoptotic protein, which was associated with drug resistance (Allen et al 2015). Bcl-2-associated transcription factor 1 (BCLAF1) showed higher expression level in cisplatin resistance non-small cell lung cancer A549 (A549/DDP) cell line than in A549 cell line as characterized by western blotting and RT-qPCR (Jiang et al 2020). Furthermore, BCLAF1 facilitated DNA damage repair by mediating the forming process of γH2A histone family member X foci formation via immunofluorescence and western blot (Jiang et al 2020).…”

A novel class of inhibitors that target SRSF10 and promote p53-mediated cytotoxicity on human colorectal cancer cells

“…Another example concerns the splicing regulator SRSF10 that is overexpressed in high grade colorectal tumors where it controls the production of BCLAF1-L, the pro-oncogenic splice variant of BCLAF1 ( 11 ). BCLAF1 modulates transcription and RNA processing, and it has been implicated in several biological processes including apoptosis and DNA repair ( 12 , 13 ). BCLAF1-L increases tumorigenesis in mice and is overproduced in high grade colorectal tumors ( 11 ).…”