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Horm Metab Res 2023; 55(08): 563-572
DOI: 10.1055/a-2084-3112
Original Article: Endocrine Research

Knockdown of CENPN Inhibits Glucose Metabolism and Induces G1 Arrest in Esophageal Cancer Cells by Regulating PI3K/AKT Signaling Pathway

Shasha Xu
1   Department of Gastroenterology, Hangzhou Ninth People's Hospital, Hangzhou, China
,
Xing Wei
2   Department of Biochemistry and Cell Biology, Youjiang Medical University for Nationalities, Baise, China
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Abstract

Esophageal carcinoma (ESCA) is a deadly malignancy with an increasing incidence year by year. The purpose of this study was to explore the function of CENPN in ESCA. Based on TCGA public data platform, the transcription level of CENPN in ESCA was analyzed. Subsequently, ESCA cells with CENPN overexpression or knockdown were constructed. The proliferation and migration levels of ESCA cells were evaluated by CCK-8, colony formation assay, and transwell analysis. Western blotting was used to detect protein levels associated with CyclinD1, CDK2, GLUT1, and PI3K/AKT signaling pathways. Cell cycle distribution was measured by flow cytometry. Glucose consumption and lactate production in ESCA cells were measured. CENPN was overexpressed in ESCA. In vitro experiments showed that CENPN promoted the proliferation and migration of ESCA cells, and upregulated the levels of CyclinD1, CDK2, and GLUT1, promoting the cell cycle process, increasing glucose consumption and lactic acid production. In addition, CENPN overexpression increased the phosphorylation levels of PI3K and AKT. The results suggest that the abnormal expression of CENPN in ESCA may enhance the malignant phenotype of ESCA cells by activating the PI3K/AKT signaling pathway. CENPN is expected to be a new target for ESCA treatment.

Key words

ESCA - CENPN - PI3K/AKT - cell cycle - glucose metabolism


Publication History

Received: 23 December 2022
Received: 01 May 2023

Accepted after revision: 01 May 2023

Accepted Manuscript online:
01 May 2023

Article published online:
13 June 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Bray F, Ferlay J, Soerjomataram I. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424
    CrossrefPubMedGoogle Scholar
  • 2 Torre LA, Bray F, Siegel RL. et al. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65: 87-108
    CrossrefPubMedGoogle Scholar
  • 3 Chen Z, Zhao M, Liang J. et al. Dissecting the single-cell transcriptome network underlying esophagus non-malignant tissues and esophageal squamous cell carcinoma. EBioMedicine 2021; 69: 103459
    CrossrefPubMedGoogle Scholar
  • 4 Su KC, Tsang MJ, Emans N. et al. CRISPR/Cas9-based gene targeting using synthetic guide RNAs enables robust cell biological analyses. Mol Biol Cell 2018; 29: 2370-2377
    CrossrefPubMedGoogle Scholar
  • 5 Zhou K, Gebala M, Woods D. et al. CENP-N promotes the compaction of centromeric chromatin. Nat Struct Mol Biol 2022; 29: 403-413
    CrossrefPubMedGoogle Scholar
  • 6 Chittori S, Hong J, Saunders H. et al. Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N. Science 2018; 359: 339-343
    CrossrefPubMedGoogle Scholar
  • 7 Weir JR, Faesen AC, Klare K. et al. Insights from biochemical reconstitution into the architecture of human kinetochores. Nature 2016; 537: 249-253
    CrossrefPubMedGoogle Scholar
  • 8 Wang Y, Li Y, Liu B. et al. Identifying breast cancer subtypes associated modules and biomarkers by integrated bioinformatics analysis. Biosci Rep 2021; 41: BSR20203200
    CrossrefPubMedGoogle Scholar
  • 9 Zhou H, Bian T, Qian L. et al. Prognostic model of lung adenocarcinoma constructed by the CENPA complex genes is closely related to immune infiltration. Pathol Res Pract 2021; 228: 153680
    CrossrefPubMedGoogle Scholar
  • 10 Qi CL, Huang ML, Zou Y. et al. The IRF2/CENP-N/AKT signaling axis promotes proliferation, cell cycling and apoptosis resistance in nasopharyngeal carcinoma cells by increasing aerobic glycolysis. J Exp Clin Cancer Res 2021; 40: 390
    CrossrefPubMedGoogle Scholar
  • 11 Oka N, Kasamatsu A, Endo-Sakamoto Y. et al. Centromere protein N participates in cellular proliferation of human oral cancer by cell-cycle enhancement. J Cancer 2019; 10: 3728-3734
    CrossrefPubMedGoogle Scholar
  • 12 Liu H, Zhang Q, Song Y. et al. Long non-coding RNA SLC2A1-AS1 induced by GLI3 promotes aerobic glycolysis and progression in esophageal squamous cell carcinoma by sponging miR-378a-3p to enhance Glut1 expression. J Exp Clin Cancer Res 2021; 40: 287
    CrossrefPubMedGoogle Scholar
  • 13 Shi Y, Fang N, Li Y. et al. Circular RNA LPAR3 sponges microRNA-198 to facilitate esophageal cancer migration, invasion, and metastasis. Cancer Sci 2020; 111: 2824-2836
    CrossrefPubMedGoogle Scholar
  • 14 Ashok A, Niyogi D, Ranganathan P. et al. The enhanced recovery after surgery (ERAS) protocol to promote recovery following esophageal cancer resection. Surg Today 2020; 50: 323-334
    CrossrefPubMedGoogle Scholar
  • 15 Hongsuphan N, Faikongngeon S, Wongtanasarasin WJSV.. Cardiac tamponade as an unusual initial presentation of squamous cell carcinoma of the esophagus 2021; 1: 4
    PubMed
  • 16 Low DE, Kuppusamy MK, Alderson D. et al. Benchmarking complications associated with esophagectomy. Ann Surg 2019; 269: 291-298
    CrossrefPubMedGoogle Scholar
  • 17 Walters DM, McMurry TL, Isbell JM. et al. Understanding mortality as a quality indicator after esophagectomy. Ann Thorac Surg 2014; 98: 506-511 discussion 511–502
    CrossrefPubMedGoogle Scholar
  • 18 Kops GJ, Weaver BA, Cleveland DW.. On the road to cancer: aneuploidy and the mitotic checkpoint. Nat Rev Cancer 2005; 5: 773-785
    CrossrefPubMedGoogle Scholar
  • 19 Wu H, Zhou Y, Wu H. et al. CENPN Acts as a novel biomarker that correlates with the malignant phenotypes of glioma cells. Front Genet 2021; 12: 732376
    CrossrefPubMedGoogle Scholar
  • 20 Kwak AW, Lee MJ, Lee MH. et al. The 3-deoxysappanchalcone induces ROS-mediated apoptosis and cell cycle arrest via JNK/p38 MAPKs signaling pathway in human esophageal cancer cells. Phytomedicine 2021; 86: 153564
    CrossrefPubMedGoogle Scholar
  • 21 Bendris N, Lemmers B, Blanchard JM.. Cell cycle, cytoskeleton dynamics and beyond: the many functions of cyclins and CDK inhibitors. Cell Cycle (Georgetown. Tex) 2015; 14: 1786-1798
    PubMedGoogle Scholar
  • 22 Lee H, Kim W, Kang HG. et al. Geranium thunbergii extract-induced G1 phase cell cycle arrest and apoptosis in gastric cancer cells. Anim Cell Syst 2020; 24: 26-33
    CrossrefPubMedGoogle Scholar
  • 23 Warburg O, Wind F, Negelein E.. The metabolism of tumors in the body. J Gen Physiol 1927; 8: 519-530
    CrossrefPubMedGoogle Scholar
  • 24 Wang Q, Yu X, Zheng Z. et al. Centromere protein N may be a novel malignant prognostic biomarker for hepatocellular carcinoma. Peer J 2021; 9: e11342
    CrossrefPubMedGoogle Scholar
  • 25 Ma L, Yao N, Chen P. et al. TRIM27 promotes the development of esophagus cancer via regulating PTEN/AKT signaling pathway. Cancer Cell Int 2019; 19: 283
    CrossrefPubMedGoogle Scholar
  • 26 Du W, Gao A, Herman JG. et al. Methylation of NRN1 is a novel synthetic lethal marker of PI3K-Akt-mTOR and ATR inhibitors in esophageal cancer. Cancer Sci 2021; 112: 2870-2883
    CrossrefPubMedGoogle Scholar
  • 27 Tseng C-HJTWJoMsH. The effect of metformin on male reproductive function and prostate: an updated review 2022; 40: 11
    PubMed