NCAPG Promotes the Malignant Progression of Endometrioid Cancer Through LEF1/SEMA7A/PI3K-AKT

Overview

Journal J Cancer

Specialty Oncology

Date 2025 Jan 2

PMID 39744480

Authors

Zhen Ren

Xiaohan Li

Chun Fu

Affiliations

Soon will be listed here.

Abstract

NCAPG promotes the progression of endometrial cancer (EC) through PI3K-AKT pathway and has potential as a novel tumor marker. However, the precise regulatory mechanism of NCAPG remains inadequately understood. In this study, we applied Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-Seq) analysis combined with chromatin immunoprecipitation-qPCR (CHIP) and Co-Immunoprecipitation (CoIP) analysis to analysis for the first time that NCAPG promotes EC cell proliferation, migration and invasion by affecting the binding of LEF1 to chromatin, thereby affecting the transcription of downstream SEMA7A. Mechanistically, SEMA7A regulated the PI3K-AKT signaling pathway by binding to the PI3K regulatory subunit p85, exerting its biological function. The NCAPG/LEF1/SEMA7A axis promoted EC tumorigenesis and progression by activating the PI3K-AKT signaling pathway. Additionally, LEF1 and SEMA7A were associated with the FIGO stage, pathological grade, and myometrial invasion in EC patients. The expressions of NCAPG, LEF1, and SEMA7A were highly consistent. Targeting this cascade may provide effective antitumor strategies to delay the progression of EC.

References

Eberlein A, Takasuga A, Setoguchi K, Pfuhl R, Flisikowski K, Fries R . Dissection of genetic factors modulating fetal growth in cattle indicates a substantial role of the non-SMC condensin I complex, subunit G (NCAPG) gene. Genetics. 2009; 183(3):951-64. PMC: 2778990. DOI: 10.1534/genetics.109.106476. View

Shi Y, Ge C, Fang D, Wei W, Li L, Wei Q . NCAPG facilitates colorectal cancer cell proliferation, migration, invasion and epithelial-mesenchymal transition by activating the Wnt/β-catenin signaling pathway. Cancer Cell Int. 2022; 22(1):119. PMC: 8922890. DOI: 10.1186/s12935-022-02538-6. View

Wilhelm T, Said M, Naim V . DNA Replication Stress and Chromosomal Instability: Dangerous Liaisons. Genes (Basel). 2020; 11(6). PMC: 7348713. DOI: 10.3390/genes11060642. View

Song Y, Wang L, Zhang L, Huang D . The involvement of semaphorin 7A in tumorigenic and immunoinflammatory regulation. J Cell Physiol. 2021; 236(9):6235-6248. DOI: 10.1002/jcp.30340. View

Liu W, Liang B, Liu H, Huang Y, Yin X, Zhou F . Overexpression of non‑SMC condensin I complex subunit G serves as a promising prognostic marker and therapeutic target for hepatocellular carcinoma. Int J Mol Med. 2017; 40(3):731-738. PMC: 5547945. DOI: 10.3892/ijmm.2017.3079. View

Bolhaqueiro A, Ponsioen B, Bakker B, Klaasen S, Kucukkose E, van Jaarsveld R . Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids. Nat Genet. 2019; 51(5):824-834. DOI: 10.1038/s41588-019-0399-6. View

Hirano T . Condensins: universal organizers of chromosomes with diverse functions. Genes Dev. 2012; 26(15):1659-78. PMC: 3418584. DOI: 10.1101/gad.194746.112. View

Buenrostro J, Giresi P, Zaba L, Chang H, Greenleaf W . Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat Methods. 2013; 10(12):1213-8. PMC: 3959825. DOI: 10.1038/nmeth.2688. View

Shelton D, Fornalik H, Neff T, Park S, Bender D, DeGeest K . The role of LEF1 in endometrial gland formation and carcinogenesis. PLoS One. 2012; 7(7):e40312. PMC: 3391280. DOI: 10.1371/journal.pone.0040312. View

10.

Hsieh T, Tsai C, Hsu C, Kuo P, Hsi E, Suen J . n-Butyl benzyl phthalate promotes breast cancer progression by inducing expression of lymphoid enhancer factor 1. PLoS One. 2012; 7(8):e42750. PMC: 3414447. DOI: 10.1371/journal.pone.0042750. View

11.

Thompson S, Compton D . Examining the link between chromosomal instability and aneuploidy in human cells. J Cell Biol. 2008; 180(4):665-72. PMC: 2265570. DOI: 10.1083/jcb.200712029. View

12.

Zhang Q, Wang Y, Xue F . ASPM, CDC20, DLGAP5, BUB1B, CDCA8, and NCAPG May Serve as Diagnostic and Prognostic Biomarkers in Endometrial Carcinoma. Genet Res (Camb). 2022; 2022:3217248. PMC: 9509287. DOI: 10.1155/2022/3217248. View

13.

Hirano T . Condensin-Based Chromosome Organization from Bacteria to Vertebrates. Cell. 2016; 164(5):847-57. DOI: 10.1016/j.cell.2016.01.033. View

14.

Garcia-Areas R, Libreros S, Amat S, Keating P, Carrio R, Robinson P . Semaphorin7A promotes tumor growth and exerts a pro-angiogenic effect in macrophages of mammary tumor-bearing mice. Front Physiol. 2014; 5:17. PMC: 3914020. DOI: 10.3389/fphys.2014.00017. View

15.

Daugherty A, Yeo R, Buenrostro J, Greenleaf W, Kundaje A, Brunet A . Chromatin accessibility dynamics reveal novel functional enhancers in . Genome Res. 2017; 27(12):2096-2107. PMC: 5741055. DOI: 10.1101/gr.226233.117. View

16.

Arai T, Okato A, Yamada Y, Sugawara S, Kurozumi A, Kojima S . Regulation of NCAPG by miR-99a-3p (passenger strand) inhibits cancer cell aggressiveness and is involved in CRPC. Cancer Med. 2018; 7(5):1988-2002. PMC: 5943442. DOI: 10.1002/cam4.1455. View

17.

Tarullo S, Hill R, Hansen K, Behbod F, Borges V, Nelson A . Postpartum breast cancer progression is driven by semaphorin 7a-mediated invasion and survival. Oncogene. 2020; 39(13):2772-2785. PMC: 7103487. DOI: 10.1038/s41388-020-1192-9. View

18.

Jongbloets B, Ramakers G, Pasterkamp R . Semaphorin7A and its receptors: pleiotropic regulators of immune cell function, bone homeostasis, and neural development. Semin Cell Dev Biol. 2013; 24(3):129-38. DOI: 10.1016/j.semcdb.2013.01.002. View

19.

Grandi F, Modi H, Kampman L, Corces M . Chromatin accessibility profiling by ATAC-seq. Nat Protoc. 2022; 17(6):1518-1552. PMC: 9189070. DOI: 10.1038/s41596-022-00692-9. View

20.

Liu C, Yan Y, Di F, Li W, Yin X, Dong L . Inhibition of NCAPG expression inactivates the Wnt/β-catenin signal to suppresses endometrial cancer cell growth in vitro. Environ Toxicol. 2021; 36(12):2512-2520. DOI: 10.1002/tox.23364. View