Article Data

  • Views 241
  • Dowloads 138

Original Research

Open Access

CENPF facilitates endometrial cancer cell progression through PI3K/AKT/mTOR pathway

  • Huan Xiao1
  • Zhi’an Zhang1
  • Chunqing Wei1
  • Dan Peng2
  • Yuge Guo3,*,

1Department of Obstetrics and Gynecology, Huanggang Central Hospital, 438000 Huanggang, Hubei, China

2Department of Clinical Laboratory, Huanggang Central Hospital, 438000 Huanggang, Hubei, China

3Department of Obstetrics and Gynecology, Yangling Demonstration Zone Hospital, 712100 Xianyang, Shaanxi, China

DOI: 10.22514/ejgo.2023.013 Vol.44,Issue 1,February 2023 pp.106-114

Submitted: 13 May 2022 Accepted: 06 July 2022

Published: 15 February 2023

*Corresponding Author(s): Yuge Guo E-mail:


Centromere protein F (CENPF) has been found to exert vital roles in various cancers, while the detailed effect of CENPF on endometrial cancer (EC) remains unclear. This study indicated that CENPF was up-regulated in EC tissue samples using The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) and Gene Expression Profiling Interactive Analysis (GEPIA) database. Quantitative real time polymerase chain reaction and western blotting assays confirmed the increased CENPF in EC cells. In addition, overexpression of CENPF promoted cell proliferation, whereas CENPF knockdown notably suppressed the proliferation of EC cells, demonstrated by Methyl Thiazolyl Tetrazolium (MTT) as well as colony formation assays. Moreover, CENPF overexpression accelerated cell cycle, migration ad invasion, whereas CENPF knockdown contributed to cell cycle arrest at G2 stage and suppressed migration and invasion in EC cells. Furthermore, western blotting analysis demonstrated that CENPF overexpression up-regulated the content of phosphorylated protein kinase B (p-AKT), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), and phosphorylated mechanistic target of rapamycin kinase (p-mTOR), while CENPF silencing notably decreased their levels, indicating that CENPF positively regulated PI3K/AKT/mTOR signaling in EC cells. In summary, this study verified that CENPF promoted EC cells progression by mediating PI3K/AKT/mTOR cascade signal in EC cell lines.


Endometrial cancer; CENPF; Proliferation; Cell cycle; PI3K/AKT/mTOR signaling pathway

Cite and Share

Huan Xiao,Zhi’an Zhang,Chunqing Wei,Dan Peng,Yuge Guo. CENPF facilitates endometrial cancer cell progression through PI3K/AKT/mTOR pathway. European Journal of Gynaecological Oncology. 2023. 44(1);106-114.


[1] Zhang L, Wan YC, Zhang ZH, Jiang Y, Gu ZY, Ma XL, et al. IGF2BP1 overexpression stabilizes PEG10 mRNA in an m6A-dependent manner and promotes endometrial cancer progression. Theranostics. 2021; 11: 1100–1114.

[2] Rak B, Marczewska JM, Wlodarski P. The role of microRNAs in endometrial cancer and influence on future therapy: focusing on miRNA-21. European Journal of Gynaecological Oncology. 2016; 37: 599–603.

[3] Felix AS, Weissfeld J, Edwards R, Linkov F. Future directions in the field of endometrial cancer research: the need to investigate the tumor microenvironment. European Journal of Gynaecological Oncology. 2010; 31: 139–144.

[4] Tran AQ, Gehrig P. Recent advances in endometrial cancer. F1000Research. 2017; 6: 81.

[5] Wang Y, Yin LL, Sun XF. CircRNA hsa_circ_0002577 accelerates endometrial cancer progression through activating IGF1R/PI3K/Akt pathway. Journal of Experimental & Clinical Cancer Research. 2020; 39: 169.

[6] Sonoda Y. Surgical treatment for apparent early stage endometrial cancer. Obstetrics & Gynecology Science. 2014; 57: 1–10

[7] Sun RM, Sun XJ, Liu H, Li PR. Knockdown of lncRNA TDRG1 inhibits tumorigenesis in endometrial carcinoma through the PI3K/AKT/mTOR pathway. OncoTargets and Therapy. 2019; 12: 10863–10872.

[8] Kong C, Zhu Z, Li Y, Xue P, Chen L. Downregulation of HOXA11 enhances endometrial cancer malignancy and cisplatin resistance via activating PTEN/AKT signaling pathway. Clinical and Translational Oncology. 2021; 23: 1334–1341.

[9] Li Q, Wang CY, Dong W, Su Y, Ma Z. WTAP facilitates progression of endometrial cancer via CAV-1/NF-κB axis. Cell Biology International. 2021; 45: 1269–1277.

[10] Liu T, Wang X, Zhai JF, Wang Q, Zhang B. Long noncoding RNA UCA1 facilitates endometrial cancer development by regulating KLF5 and RXFP1 gene expressions. Cancer Biotherapy & Radiopharmaceuticals. 2021; 36: 521–533.

[11] Liao H, Winkfein RJ, Mack G, Rattner JB, Yen TJ. CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis. Journal of Cell Biology. 1995; 130: 507–518.

[12] Zhu X, Mancini MA, Chang KH, Liu CY, Chen CF, Shan B, et al. Characterization of a novel 350-kilodalton nuclear phosphoprotein that is specifically involved in mitotic-phase progression. Molecular and Cellular Biology. 1995; 15: 5017–5029.

[13] Sun J, Huang J, Lan J, Zhou K, Gao Y, Song Z, et al. Overexpression of CENPF correlates with poor prognosis and tumor bone metastasis in breast cancer. Cancer Cell International. 2019; 19: 264.

[14] Huang YG, Li D, Wang L, Su XM, Tang XB. CENPF/CDK1 signaling pathway enhances the progression of adrenocortical carcinoma by regulating the G2/M-phase cell cycle. Journal of Translational Medicine. 2022; 20: 78.

[15] O’Brien SL, Fagan A, Fox EJP, Millikan RC, Culhane AC, Brennan DJ, et al. CENP-F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer. International Journal of Cancer. 2007; 120: 1434–1443.

[16] Yang X, Miao BS, Wei CY, Dong RZ, Gao PT, Zhang XY, et al. Lymphoid‐specific helicase promotes the growth and invasion of hepatocellular carcinoma by transcriptional regulation of centromere protein F expression. Cancer Science. 2019; 110: 2133–2144.

[17] Chen E, Qin X, Peng K, Li Q, Tang C, Wei Y, et al. HnRNPR-CCNB1/CENPF axis contributes to gastric cancer proliferation and metastasis. Aging. 2019; 11: 7473–7491.

[18] Liu Y, Chen P, Li M, Fei H, Huang J, Zhao T, et al. Comprehensive analysis of the control of cancer stem cell characteristics in endometrial cancer by network analysis. Computational and Mathematical Methods in Medicine. 2021; 2021: 6653295.

[19] Shorning BY, Dass MS, Smalley MJ, Pearson HB. The PI3K-AKT-mTOR pathway and prostate cancer: at the crossroads of AR, MAPK, and WNT signaling. International Journal of Molecular Sciences. 2020; 21: 4507.

[20] Ediriweera MK, Tennekoon KH, Samarakoon SR. Role of the PI3K/AKT/mTOR signaling pathway in ovarian cancer: Biological and therapeutic significance. Seminars in Cancer Biology. 2019; 59: 147–160.

[21] Guerrero-Zotano A, Mayer IA, Arteaga CL. PI3K/AKT/mTOR: role in breast cancer progression, drug resistance, and treatment. Cancer and Metastasis Reviews. 2016; 35: 515–524.

[22] Slomovitz BM, Coleman RL. The PI3K/AKT/mTOR Pathway as a therapeutic target in endometrial cancer. Clinical Cancer Research. 2012; 18: 5856–5864.

[23] Zhang YY, Zhang F, Zhang YS, Thakur K, Zhang JG, Liu Y, et al. Mechanism of Juglone-induced cell cycle arrest and apoptosis in ishikawa human endometrial cancer cells. Journal of Agricultural and Food Chemistry. 2019; 67: 7378–7389.

[24] Hsin IL, Shen HP, Chang HY, Ko JL, Wang PH. Suppression of PI3K/Akt/mTOR/c-Myc/mtp53 positive feedback loop induces cell cycle arrest by dual PI3K/mTOR inhibitor PQR309 in endometrial cancer cell lines. Cells. 2021; 10: 2916.

[25] Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi BVSK, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 2017; 19: 649–658.

[26] Ling S, Zhang L, Qian Y, Liu Z, Mao Z, Zhang Q. Curcumol inhibits PDGF-BB-induced proliferation and migration of airway smooth muscle cells by suppressing ERK/CREB pathway. Allergologia et Immunopathologia. 2022; 50: 17–24.

[27] Yang X, Gong J, Cai X, Yuan Y. Overexpression of HIC1 plays a protective effect on renal cell injury caused by lipopolysaccharide by inhibiting IL-6/STAT3 pathway. Signa Vitae. 2022; 18: 147–153.

[28] Wang X, Chen T, Deng Z, Gao W, Liang T, Qiu X, et al. Melatonin promotes bone marrow mesenchymal stem cell osteogenic differentiation and prevents osteoporosis development through modulating circ_0003865 that sponges miR-3653-3p. Stem Cell Research & Therapy. 2021; 12: 150.

[29] Sang M, Wu M, Meng L, Zheng Y, Gu L, Liu F, et al. Identification of epithelial-mesenchymal transition-related circRNA-miRNA-mRNA ceRNA regulatory network in breast cancer. Pathology-Research and Practice. 2020; 216: 153088.

[30] Chen Q, Xu H, Zhu J, Feng K, Hu C. LncRNA MCM3AP-as1 promotes breast cancer progression via modulating miR-28-5p/CENPF axis. Biomedicine & Pharmacotherapy. 2020; 128: 110289.

[31] Han Y, Xu S, Cheng K, Diao C, Liu S, Zou W, et al. CENPF promotes papillary thyroid cancer progression by mediating cell proliferation and apoptosis. Experimental and Therapeutic Medicine. 2021; 21: 401.

[32] Edgar R, Domrachev M, Lash AE. Gene expression omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Research. 2002; 30: 207–210.

[33] Shahid M, Kim M, Lee MY, Yeon A, You S, Kim HL, et al. Downregulation of CENPF remodels prostate cancer cells and alters cellular metabolism. Proteomics. 2019; 19: e1900038.

[34] Yuan J, Gu L, Chen L, Yin Y, Fan B. Annexin a8 regulated by lncRNA-TUG1/miR-140-3p axis promotes bladder cancer progression and metastasis. Molecular Therapy Oncolytics. 2021; 22: 36–51.

[35] Li P, You S, Nguyen C, Wang Y, Kim J, Sirohi D, et al. Genes involved in prostate cancer progression determine MRI visibility. Theranostics. 2018; 8: 1752–1765.

[36] Zhou J, Jiang Y, Chen H, Wu Y, Zhang L. Tanshinone I attenuates the malignant biological properties of ovarian cancer by inducing apoptosis and autophagy via the inactivation of PI3K/AKT/mTOR pathway. Cell Proliferation. 2020; 53: e12739.

[37] Shahcheraghi SH, Tchokonte-Nana V, Lotfi M, Lotfi M, Ghorbani A, Sadeghnia HR. Wnt/beta-catenin and PI3K/Akt/mTOR signaling pathways in glioblastoma: two main targets for drug design: a review. Current Pharmaceutical Design. 2020; 26: 1729–1741.

[38] Roncolato F, Lindemann K, Willson ML, Martyn J, Mileshkin L. PI3K/AKT/mTOR inhibitors for advanced or recurrent endometrial cancer. Cochrane database of systematic reviews. 2019; 10: CD012160.

[39] Liu H, Zhang L, Zhang X, Cui Z. PI3K/AKT/mTOR pathway promotes progestin resistance in endometrial cancer cells by inhibition of autophagy. OncoTargets and Therapy. 2017; 10: 2865–2871.

[40] Cao X, He GZ. Knockdown of CLDN6 inhibits cell proliferation and migration via PI3K/AKT/mTOR signaling pathway in endometrial carcinoma cell line HEC-1-B. OncoTargets and Therapy. 2018; 11: 6351–6360.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time