|Table of Contents|

Effect of ENO1 on the proliferation and apoptosis of acute myeloid leukemia cells

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

Issue:
2023 24
Page:
4524-4531
Research Field:
Publishing date:

Info

Title:
Effect of ENO1 on the proliferation and apoptosis of acute myeloid leukemia cells
Author(s):
SONG Peng1; 2; SHI Hewen1; ZOU Ying1; LI Minjing1; 2; YANG Chunyan2
1.Institute of Integrated Medicine,Binzhou Medical University,Shandong Yantai 264003,China；2.Medicine & Pharmacy Research Center,Binzhou Medical University,Shandong Yantai 264003,China.
Keywords:
ENO1; acute myeloid leukemia; apoptosis; shRNA
PACS:
R733.71
DOI:
10.3969/j.issn.1672-4992.2023.24.007
Abstract:
Objective:To investigate the role and molecular mechanism of Enolase 1 (ENO1) in regulating cell metabolism in acute myeloid leukemia (AML).Methods:The expression of ENO1 in AML patients was analyzed from GEO,TCGA and other databases.The relationship between gene expression levels and patient overall survival was analyzed by applying Kaplan-Meier analysis.ENO1 shRNA lentiviral plasmid system was constructed,then infected MV4-11 and NB4 cell lines respectively.Western blot method was used to detect the knockdown efficiency of ENO1.CCK-8 method were used to detect its effect on AML cell growth.Annexin V-PE/7-AAD staining was used to explore the apoptosis on AML cell.GO and KEGG protein enrichment methods were used to analyze the function of ENO1 in cells and its related signaling pathways.Results:Analysis through GEO and TCGA databases showed that ENO1 was significantly highly expressed in most AML patients (P＜0.05，P＜0.01),but not in patients with other types of leukemia.ENO1 was significantly highly expressed in AML cells,in leukemic stem cells,and in hematopoietic stem cells in AML mouse models (P＜0.001).Kaplan-Meier analysis showed that patients with high ENO1 expression had significantly lower overall survival than those with low ENO1 expression (P＜0.05，HR>1).Knockdown of ENO1 significantly inhibited AML cell growth and induced AML cell apoptosis (P＜0.01).Enrichment analysis revealed that in AML cells,ENO1 was mainly involved in histone methylation,RNA interference complex formation and glucose metabolism.Its negatively coexpression genes were principally enriched in autophagy and FOXO signaling pathway.Conclusion:ENO1 is highly expressed in AML patients,especially in AML stem cells and is negatively correlated with overall survival.Moreover,high expression of ENO1 can promote the growth of AML cells and inhibit the apoptosis of AML cells.ENO1 is expected to provide some reference for the treatment and prognosis of AML patients.

References:

［1］ VAKITI A,MEWAWALLA P.Acute myeloid leukemia［M］.StatPearls:StatPearls Publishing LLC,2022:5-20.
［2］ YILMAZ M,WANG F,LOGHAVI S,et al.Late relapse in acute myeloid leukemia (AML):clonal evolution or therapy-related leukemia［J］.Blood Cancer J,2019,9(2):7.
［3］ KIYOI H,KAWASHIMA N,ISHIKAWA Y.FLT3 mutations in acute myeloid leukemia:Therapeutic paradigm beyond inhibitor development［J］.Cancer Sci,2020,111(2):312-322.
［4］ LAINEZ-GONZLEZ D,SERRANO-LPEZ J,ALONSO-DOMNGUEZ JM.Understanding the hedgehog signaling pathway in acute myeloid leukemia stem cells:A necessary step toward a cure［J］.Biology,2021,10(4):255.
［5］ PILI PG,TANG C,MILLS GB,et al.State-of-the-art strategies for targeting the DNA damage response in cancer［J］.Nat Rev Clin Oncol,2019,16(2):81-104.
［6］ VALENT P,SADOVNIK I,EISENWORT G,et al.Immunotherapy-based targeting and elimination of leukemic stem cells in AML and CML［J］.Int J Mol Sci,2019,20(17):4233.
［7］ ALMAJALI B,JOHAN MF,AL-WAJEEH AS,et al.Gene expression profiling and protein analysis reveal suppression of the C-Myc oncogene and inhibition JAK/STAT and PI3K/AKT/mTOR signaling by thymoquinone in acute myeloid leukemia cells［J］.Pharmaceuticals (Basel,Switzerland),2022,15(3):307.
［8］ AL-RAWASHDE FA,AL-WAJEEH AS,VISHKAEI MN,et al.Thymoquinone inhibits JAK/STAT and PI3K/Akt/ mTOR signaling pathways in MV4-11 and K562 myeloid leukemia cells［J］.Pharmaceuticals (Basel,Switzerland),2022,15(9):1123.
［9］ PEPE F,BILL M,PAPAIOANNOU D,et al.Targeting Wnt signaling in acute myeloid leukemia stem cells［J］.Haematologica,2022,107(1):307-311.
［10］ PENG C,HOU ST,DENG CX,et al.Function of DHX33 in promoting Warburg effect via regulation of glycolytic genes［J］.J Cell Physiol,2021,236(2):981-996.
［11］ AGUAYO-ORTIZ R,MEZA-CERVANTEZ P,CASTILLO R,et al.Insights into the Giardia intestinalis enolase and human plasminogen interaction［J］.Mol Biosyst,2017,13(10):2015-2023.
［12］ HOU JY,CAO J,GAO LJ,et al.Upregulation of α enolase (ENO1) crotonylation in colorectal cancer and its promoting effect on cancer cell metastasis［J］.Biochem Biophys Res Commun,2021,578:77-83.
［13］ LI M,HAO S,LI C,et al.Elevated SH3BP5 correlates with poor outcome and contributes to the growth of acute myeloid leukemia cells［J］.Biomolecules,2019,9(9):505.
［14］ HAO S,YANG C,SONG P,et al.CLDN4 promotes growth of acute myeloid leukemia cells via regulating AKT and ERK1/2 signaling［J］.Biochem Biophys Res Commun,2022,619:137-143.
［15］ DENG T,SHEN P,LI A,et al.CCDC65 as a new potential tumor suppressor induced by metformin inhibits activation of AKT1 via ubiquitination of ENO1 in gastric cancer［J］.Theranostics,2021,11(16):8112-8128.
［16］ ZHANG G,ZHAO X,LIU W,et al.NEDD4L inhibits glycolysis and proliferation of cancer cells in oral squamous cell carcinoma by inducing ENO1 ubiquitination and degradation［J］.Cancer Biol Ther,2022,23(1):243-253.
［17］ YU S,LI N,HUANG Z,et al.A novel lncRNA,TCONS_00006195,represses hepatocellular carcinoma progression by inhibiting enzymatic activity of ENO1［J］.Cell Death Dis,2018,9(12):1184.
［18］ LI J,HU ZQ,YU SY,et al.CircRPN2 inhibits aerobic glycolysis and metastasis in hepatocellular carcinoma［J］.Cancer Res,2022,82(6):1055-1069.
［19］ LUO JT,WANG YF,WANG Y,et al.A Circular RNA,hsa_circ_0018180 (circPARD3),triggers glycolysis and promotes malignancy of head and neck squamous cell carcinoma through the miR-5194/ENO1 Axis［J］.Biochem Genet,2022,61(1):316-335.
［20］ MA J,ZHAO W,ZHANG H,et al.Long non-coding RNA ANRIL promotes chemoresistance in triple-negative breast cancer via enhancing aerobic glycolysis［J］.Life Sci,2022,306:120810.
［21］ LI Y,LI Y,LUO J,et al.FAM126A interacted with ENO1 mediates proliferation and metastasis in pancreatic cancer via PI3K/AKT signaling pathway［J］.Cell Death Discov,2022,8(1):248.
［22］ ZHAN P,ZHAO S,YAN H,et al.α-enolase promotes tumorigenesis and metastasis via regulating AMPK/mTOR pathway in colorectal cancer［J］.Mol Carcinog,2017,56(5):1427-1437.
［23］ GOU Y,LI F,HUO X,et al.ENO1 monoclonal antibody inhibits invasion,proliferation and clone formation of cervical cancer cells［J］.Am J Cancer Res,2021,11(5):1946-1961.
［24］ HUANG Q,ZHANG H,BAI LP,et al.Novel ginsenoside derivative 20(S)-Rh2E2 suppresses tumor growth and metastasis in vivo and in vitro via intervention of cancer cell energy metabolism［J］.Cell Death Dis,2020,11(8):1-19.
［25］ HUANG Z,YAN Y,WANG T,et al.Identification of ENO1 as a prognostic biomarker and molecular target among ENOs in bladder cancer［J］.J Transl Med,2022,20(1):315.
［26］ LIU W,WANG Q,CHANG J,et al.Serum proteomics unveil characteristic protein diagnostic biomarkers and signaling pathways in patients with esophageal squamous cell carcinoma［J］.Clin Proteomics,2022,19(1):18.
［27］ CAPPELLO P,PRINCIPE M,BULFAMANTE S,et al.Alpha-enolase (ENO1),a potential target in novel immunotherapies［J］.Front Biosci (Landmark Ed),2017,22(5):944-959.
［28］ XU B,ZHOU Z,WEN Y,et al.The immunometabolic landscape of the bone marrow microenvironment in acute myeloid leukemia［J］.Exp Hematol Oncol,2022,11(1):81.
［29］ ZHANG C,ZHANG K.ENO1 promotes antitumor immunity by destabilizing PD-L1 in NSCLC［J］.Cell Mol Immunol,2021,18(8):2045-2047.

Memo

Memo:
山东省自然科学基金(编号：ZR2019PH080,ZR2020MH120)
Last Update: 1900-01-01