|Table of Contents|

SLC7A11 expression in patients with acute myeloid leukemia and the mechanism of inhibiting HL-60 cells proliferation

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 02
Page:
316-319
Research Field:
Publishing date:

Info

Title:
SLC7A11 expression in patients with acute myeloid leukemia and the mechanism of inhibiting HL-60 cells proliferation
Author(s):
WANG Yayun; ZHANG Hongyan; MA Shupei; HAO Lumei; LIU Shuangshuang; YU Shuyuan; ZHONG Yuping
Qingdao Municipal Hospital,Shandong Qingdao 266071,China.
Keywords:
acute myeloid leukemia; ferroptosis; SLC7A11; Erastin
PACS:
R733.71
DOI:
10.3969/j.issn.1672-4992.2023.02.022
Abstract:
Objective:To investigate the effect of SLC7A11 siRNA and Erastin on the cell viability of acute myeloid leukemia (AML) cells HL-60.Methods:The data of AML patients in The Cancer Genome Atlas (TCGA) were analyzed by bioinformatics method to compare the prognosis of patients with different expression levels of SLC7A11.The expression levels of SLC7A11 mRNA and protein in patients with AML and iron deficiency anemia (IDA) were detected by quantitative Real-time PCR （qRT-PCR） and Western-blot.HL-60 cells were cultured and transfected with virus mediated siRNA for SLC7A11 silencing (siSLC7A11).HL-60 cells were also treated with Erastin or DMSO.The mRNA and protein expression levels of SLC7A11 in HL-60 cells and siSLC7A11 cells were detected by qRT-PCR and Western-blot.Cell viability was detected by CCK-8 kit.Results:The mRNA and protein expression levels of SLC7A11 in AML patients were significantly higher than those in IDA patients (P＜0.05).The mRNA and protein expression levels of SLC7A11 in siSLC7A11 cells were significantly lower than those in the control group (P＜0.05).The proliferation rate of siSLC7A11 cells was significantly lower than theose in control group (P＜0.05).Conclusion:The expression of SLC7A11 is increased in AML patients.Inhibition of SLC7A11 by siRNA or Erastin can significantly inhibit the proliferation of AML HL-60 cells.SLC7A11 gene may become a new target for the treatment of AML.

References:

[1] WEINBERG OK,SOHANI AR,BHARGAVA P,et al.Diagnostic work-up of acute myeloid leukemia［J］.Am J Hematol,2017,92(3):317-321.
[2] DOHNER H,ESTEY E,GRIMWADE D,et al.Diagnosis and management of AML in adults:2017 ELN recommendations from an international expert panel［J］.Blood,2017,129(4):424-447.
[3] STONE RM,MANDREKAR SJ,SANFORD BL,et al.Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation［J］.N Engl J Med,2017,377(5):454-464.
[4] DINARDO CD,PRATZ K,PULLARKAT V,et al.Venetoclax combined with decitabine or azacitidine in treatment-naive,elderly patients with acute myeloid leukemia［J］.Blood,2019,133(1):7-17.
[5] KOPPULA P,ZHANG Y,ZHUANG L,et al.Amino acid transporter SLC7A11/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer［J］.Cancer Commun (Lond),2018,38(1):12.
[6] KOPPULA P,ZHUANG L,GAN B.Cystine transporter SLC7A11/xCT in cancer:ferroptosis,nutrient dependency,and cancer therapy［J］.Protein Cell,2021,12(8):599-620.
[7] KOPPULA P,ZHANG Y,SHI J,et al.The glutamate/cystine antiporter SLC7A11/xCT enhances cancer cell dependency on glucose by exporting glutamate［J］.J Biol Chem,2017,292(34):14240-14249.
[8] ZHAO X,LI Y,WU H.A novel scoring system for acute myeloid leukemia risk assessment based on the expression levels of six genes［J］.Int J Mol Med,2018,42(3):1495-1507.
[9] ZHAO Y,LI Y,ZHANG R,et al.The role of Erastin in ferroptosis and its prospects in cancer therapy［J］.Onco Targets Ther,2020,13:5429-5441.
[10] STOCKWELL BR,FRIEDMANN ANGELI JP,BAYIR H,et al.Ferroptosis:A regulated cell death nexus linking metabolism,redox biology,and disease［J］.Cell,2017,171(2):273-285.
[11] STOCKWELL BR,JIANG X.The chemistry and biology of ferroptosis［J］.Cell Chem Biol,2020,27(4):365-375.
[12] BEBBER CM,MLLER F,CLEMENTE LP,et al.Ferroptosis in cancer cell biology［J］.Cancers,2020,12(1):164.
[13] YANG WS,SRIRAMARATNAM R,WELSCH ME,et al.Regulation of ferroptotic cancer cell death by GPX4［J］.Cell,2014,156(1-2):317-331.
[14] URSINI F,MAIORINO M.Lipid peroxidation and ferroptosis:The role of GSH and GPx4［J］.Free Radic Biol Med,2020,152:175-185.
[15] SATO H,TAMBA M,ISHII T,et al.Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins［J］.J Biol Chem,1999,274(17):11455-11458.
[16] CHEN X,LI J,KANG R,et al.Ferroptosis:machinery and regulation［J］.Autophagy,2020,26:1-28.
[17] CHIO IIC,TUVESON DA.ROS in cancer:the burning question［J］.Trends Mol Med,2017,23(5):411-429.
[18] DIXON SJ,PATEL DN,WELSCH M,et al.Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis［J］.Elife,2014,3:e02523.
[19] ZHANG Y,SHI J,LIU X,et al.BAP1 links metabolic regulation of ferroptosis to tumour suppression［J］.Nat Cell Biol,2018,20(10):1181-1192.
[20] JIANG L,KON N,LI TY,et al.Ferroptosis as a p53-mediated activity during tumour suppression［J］.Nature,2015,520(7545):57.

Memo

Memo:
-
Last Update: 1900-01-01