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

GAO Li; LI Xiaoming; YANG Bo; QIN Ying; CHENG Dong; ZHENG Lifei; LI Li

doi:10.7619/jcmp.20214581

Journal of Clinical Medicine in Practice > 2022 > 26(8): 66-70, 75. > DOI: 10.7619/jcmp.20214581

GAO Li, LI Xiaoming, YANG Bo, QIN Ying, CHENG Dong, ZHENG Lifei, LI Li. Long non-coding RNA CBR3-AS1 mediates the mechanism of cytarabine resistance in leukemia cells through the PI3K/AKT/mTOR/S6K pathway[J]. Journal of Clinical Medicine in Practice, 2022, 26(8): 66-70, 75. DOI: 10.7619/jcmp.20214581

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

1.
Department of Hematology, Ya′an People′s Hospital in Sichuan Province, Ya′an, Sichuan, 625000
2.
Department of Hematology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000
3.
Nanchong Central Hospital in Sichuan Province, Nanchong, Sichuan, 737003

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Received Date: November 21, 2021
Available Online: April 27, 2022

Graphical Abstract

Abstract

Abstract

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.
- long non-coding RNA CBR3-AS1,
- acute myelocytic leukemia,
- cytarabine,
- drug resistance,
- PI3K/AKT/mTOR/S6K pathway

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References (17)

References

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

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