Long non-coding RNA CBR3-AS1 mediates the mechanism of cytarabine resistance in leukemia cells through the PI3K/AKT/mTOR/S6K pathway

Objective To investigate the possible mechanism of long non-coding RNA (lncRNA) CBR3-AS1 mediating cytarabine resistance in acute myeloid leukemia (AML) cells through PI3K/AKT/mTOR/S6K pathway.

Methods Drug resistance models were established in two AML cell strains K562 and HL-60, named as K562-R and HL-60-R, respectively. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of lncRNA CBR3-AS1 in K562-R and HL-60-R. LncRNA CBR3-AS1 was overexpressed by plasmids in the K562 and HL-60 cell strains; lncRNA CBR3-AS1 expression was knocked down by siRNA in K562-R and HL-60-R cell strains, and the 50% inhibitory concentration (IC₅₀) of cytarabine was calculated. K562-R and HL-60-R cell lines, siRNA was used to knock down the expression of lncRNA CBR3-AS1. Western blot was used to detect the activation of PI3K/AKT/mTOR/S6K pathway.

Results Compared with K562 and HL-60 cell strains, the expressions of lncRNA CBR3-AS1 in K562-R and HL-60-R cell strains were significantly increased (P < 0.05). Overexpression of lncRNA CBR3-AS1 increased the IC₅₀ of cytarabine to over 1 000 μmol/L (P < 0.05). After knock down lncRNA CBR3-AS1, the IC₅₀ of cytarabine in drug-resistant cell strains K562-R and HL-60-R were significantly reduced to 21.27 μmol/L and 12.10 μmol/L (P < 0.05), respectively. Overexpression of lncRNA CBR3-AS1 significantly increased the phosphorylation levels of PI3K, AKT, mammalian target of rapamycin (mTOR) and S6K proteins (P < 0.05). Knockdown lncRNA CBR3-AS1 significantly reduced the phosphorylation levels of PI3K, AKT, mTOR and S6K proteins (P < 0.05).

Conclusion LncRNA CBR3-AS1 may mediate the resistance of AML cells to cytarabine by activating the PI3K/AKT/mTOR/S6K pathway.