Characterization of the impact of the MYBBP1A gene and rs3809849 on asparaginase sensitivity and cellular functions.
Rachid AbajiVincent RouxIsmahène Reguieg YssaadPaloma KalegariVincent GagnéRomain GioiaGerardo FerbeyreChristian BeauséjourMaja KrajinovicPublished in: Pharmacogenomics (2022)
Aims: To investigate the role of MYBBP1A gene and rs3809849 in pancreatic cancer (PANC1) and lymphoblastic leukemia (NALM6) cell lines and their response to asparaginase treatment. Materials & methods: The authors applied CRISPR-Cas9 to produce MYBBP1A knock-out (KO) and rs3809849 knock-in (KI) cell lines. The authors also interrogated rs3809849's impact on PANC1 cells through allele-specific overexpression. Results: PANC1 MYBBP1A KO cells exhibited lower proliferation capacity (p ≤ 0.05), higher asparaginase sensitivity (p = 0.01), reduced colony-forming potential (p = 0.001), cell cycle blockage in S phase, induction of apoptosis and remarkable morphology changes suggestive of an epithelial-mesenchymal transition. Overexpression of the wild-type (but not the mutant) allele of MYBBP1A -rs3809849 in PANC1 cells increased asparaginase sensitivity. NALM6 MYBBP1A KO displayed resistance to asparaginase (p < 0.0001), whereas no effect for rs3809849 KI was noted. Conclusions: MYBBP1A is important for regulating various cellular functions, and it plays, along with its rs3809849 polymorphism, a tissue-specific role in asparaginase treatment response.
Keyphrases
- cell cycle arrest
- induced apoptosis
- cell cycle
- epithelial mesenchymal transition
- endoplasmic reticulum stress
- cell proliferation
- crispr cas
- signaling pathway
- cell death
- wild type
- oxidative stress
- pi k akt
- copy number
- genome wide
- squamous cell carcinoma
- neoadjuvant chemotherapy
- acute myeloid leukemia
- radiation therapy
- bone marrow
- gene expression
- lymph node
- dna methylation
- climate change
- smoking cessation