Knockout KHDRBS3 inhibits cell proliferation and glucocorticoid resistance in acute lymphoblastic leukemia

Background Drug resistance is one of the major causes of the acute lymphoblastic leukemia (ALL) relapse. Although KH RNA-binding domain containing, signal transduction associated 3 (KHDRBS3) has been revealed to be associated with drug resistance, its role and mechanism in the resistant of ALL is still unclear. Objective This study aimed to analyze the role of KHDRBS3 in the proliferation, apoptosis and dexamethasone (Dex) resistance of ALL through the loss-of-function and gain-of-function assays. The cell proliferation was evaluated by cell counting kit-8 (CCK-8) and colony-formation assays. The apoptosis and G(0)/G(1) phase arrest were determined by flow cytometry and western blot assays. In addition, the relative RNA and protein expression of KHDRBS3 was examination by quantitative reverse transcriptase-PCR (qRT-PCR) and western blot assays. Moreover, the role of Wnt/beta-catenin/c-MYC signaling axis was evaluated by western blot assays. Results DEX ranged from 0.5 to 10 mu M had no effect on the viability of both Reh and CEM/C1 cell lines, while significantly reduced the viability of CCRF-CEM and BALL-1 cell lines at 24 and 48 h. Meanwhile, both relative KHDRBS3 transcriptional and translational expressions were enhanced in Reh and CEM/C1 cell lines, whereas downregulated in CCRF-CEM and BALL-1 cell lines. Moreover, KHDRBS3 interference observably diminished DEX-induced cell viability and the colony-formation area with the enhanced apoptosis and G(0)/G(1) phase arrest of Reh and CEM/C1 cells, while overexpression of KHDRBS3 resulted in the opposite outcomes in CCRF-CEM and BALL-1 cells. More importantly, downregulation of KHDRBS3 notably diminished the relative protein expressions of Wnt3a, beta-catenin and c-MYC, vice versa. Conclusion KHDRBS3 knockdown inhibited cell proliferation and glucocorticoid resistance in ALL, which involved in Wnt/beta-catenin/c-MYC signaling pathway.