Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Ovarian Research
Published in: Journal of Ovarian Research 1/2016

Open Access 01-12-2016 | Research

UHRF1 gene silencing inhibits cell proliferation and promotes cell apoptosis in human cervical squamous cell carcinoma CaSki cells

Authors: Ting-Ting Ge, Meng Yang, Zhuo Chen, Ge Lou, Tao Gu

Published in: Journal of Ovarian Research | Issue 1/2016

Login to get access

Abstract

Background

Up-regulation of UHRF1 has been observed in a variety of cancers and appears to serve as an independent prognostic factor.

Objective

To explore the effect of UHRF1 gene silencing on apoptosis and proliferation of cervical squamous cell carcinoma (CSCC) CaSki cells.

Methods

This study consisted of 47 CSCC tissues and 40 normal cervical tissues. The CaSki cells were assigned into Blank group (CaSki cells not transfected), NC group (CaSki cells transfected with control siRNA), and UHRF1 Silence group (CaSki cells transfected with UHRF1 siRNA). qRT-PCR and Western blot were used for UHRF1 mRNA and protein expressions, CKK-8 assay for cell proliferation, flow cytometry for cell cycle and apoptosis, Western blot for expressions of apoptosis-related proteins. Nude mice tumor transplant experiment was performed.

Results

UHRF1 exhibited higher mRNA and protein expressions in the CSCC tissues than normal cervical tissues (both P < 0.05). The cell proliferation ability in the UHRF1 Silence group was reduced when compared with the Blank group and the NC group, the cells at S-G2M stage in the UHRF1 Silence group were dropped when compared with the Blank group and the NC group (P < 0.05), while the cells at G0/G1 stage were elevated (P < 0.05), and the proportion of Annexin V positive cells in the UHRF1 Silence group was increased in comparison with the Blank group and the NC group (P < 0.05). Nude mice tumor transplant experiment indicated that the growth rate and weight of tumor in the Blank group and NC group was higher and heavier than the UHRF1 Silence group (P < 0.05).

Conclusion

UHRF1 showed a high expression in CSCC and UHRF1 silencing can reduce proliferation and enhance apoptosis of the CaSki cells.
Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
2.
Li Z, Yang Y, Gao Y, Wu X, Yang X, Zhu Y, Yang H, Wu L, Yang C, Song L. Elevated expression of flotillin-1 is associated with lymph node metastasis and poor prognosis in early-stage cervical cancer. Am J Cancer Res. 2016;6:38–50.
3.
Colombo N, Carinelli S, Colombo A, Marini C, Rollo D, Sessa C, E. G. W. Group. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23 Suppl 7:vii27–32.PubMed
4.
Jiang P, Ren YL, Li JL, Luo J. Girdin expression in cervical carcinoma and its role in the malignant properties of HeLa cells. Oncol Lett. 2016;11:2440–4.PubMedPubMedCentral
5.
Li XL, Xu JH, Nie JH, Fan SJ. Exogenous expression of UHRF1 promotes proliferation and metastasis of breast cancer cells. Oncol Rep. 2012;28:375–83.PubMed
6.
Yan F, Wang X, Shao L, Ge M, Hu X. Analysis of UHRF1 expression in human ovarian cancer tissues and its regulation in cancer cell growth. Tumour Biol. 2015;36:8887–93.CrossRefPubMed
7.
8.
Alhosin M, Sharif T, Mousli M, Etienne-Selloum N, Fuhrmann G, Schini-Kerth VB, et al. Down-regulation of UHRF1, associated with re-expression of tumor suppressor genes, is a common feature of natural compounds exhibiting anti-cancer properties. J Exp Clin Cancer Res. 2011;30:41.CrossRefPubMedPubMedCentral
9.
Unoki M, Kelly JD, Neal DE, Ponder BA, Nakamura Y, Hamamoto R. UHRF1 is a novel molecular marker for diagnosis and the prognosis of bladder cancer. Br J Cancer. 2009;101:98–105.CrossRefPubMedPubMedCentral
10.
Pi JT, Lin Y, Quan Q, Chen LL, Jiang LZ, Chi W, et al. Overexpression of UHRF1 is significantly associated with poor prognosis in laryngeal squamous cell carcinoma. Med Oncol. 2013;30:613.CrossRefPubMed
11.
Mahajan A, Engineer R, Chopra S, Mahanshetty U, Juvekar SL, Shrivastava SK, et al. Role of 3 T multiparametric-MRI with BOLD hypoxia imaging for diagnosis and post therapy response evaluation of postoperative recurrent cervical cancers. Eur J Radiol Open. 2016;3:22–30.CrossRefPubMed
12.
Matsushita, R, Yoshino H, Enokida H, Goto Y, Miyamoto K, Yonemori M., Inoguchi S, Nakagawa M Sek Ni. Regulation of UHRF1 by dual-strand tumor-suppressor microRNA-145 (miR-145-5p and miR-145-3p): Inhibition of bladder cancer cell aggressiveness. Oncotarget. 2016; doi:10.​18632/​oncotarget.​8668.
13.
Wan X, Yang S, Huang W, Wu D, Chen H, Wu M, et al. UHRF1 overexpression is involved in cell proliferation and biochemical recurrence in prostate cancer after radical prostatectomy. J Exp Clin Cancer Res. 2016;35:34.CrossRefPubMedPubMedCentral
14.
Bostick M, Kim JK, Esteve PO, Clark A, Pradhan S, Jacobsen SE. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science. 2007;317:1760–4.CrossRefPubMed
15.
Arita K, Ariyoshi M, Tochio H, Nakamura Y, Shirakawa M. Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism. Nature. 2008;455:818–21.CrossRefPubMed
16.
Avvakumov GV, Walker JR, Xue S, Li Y, Duan S, Bronner C, Arrowsmith CH, Dhe-Paganon S. Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1. Nature. 2008;455:822–5.
17.
Sharif J, Muto M, Takebayashi S, Suetake I, Iwamatsu A, Endo TA, Shinga J, Mizutani-Koseki Y, Toyoda T, Okamura K, Tajima S, Mitsuya K, Okano M, Koseki H. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature. 2007;450:908–12.
18.
Krifa M, Alhosin M, Muller CD, Gies JP, Chekir-Ghedira L, Ghedira K, Mely Y, Bronner C, Mousli M. Limoniastrum guyonianum aqueous gall extract induces apoptosis in human cervical cancer cells involving p16 INK4A re-expression related to UHRF1 and DNMT1 down-regulation. J Exp Clin Cancer Res. 2013;32:30.
19.
Jenkins Y, Markovtsov V, Lang W, Sharma P, Pearsall D, Warner J, Franci C, Huang B, Huang J, Yam GC, Vistan JP, Pali E, Vialard J, Janicot M, Lorens JB, Payan DG, Hitoshi Y. Critical role of the ubiquitin ligase activity of UHRF1, a nuclear RING finger protein, in tumor cell growth. Mol Biol Cell. 2005;16:5621–9.
20.
Arima Y, Hirota T, Bronner C, Mousli M, Fujiwara T, Niwa S, Ishikawa H, Saya H. Down-regulation of nuclear protein ICBP90 by p53/p21Cip1/WAF1-dependent DNA-damage checkpoint signals contributes to cell cycle arrest at G1/S transition. Genes Cells. 2004;9:131–42.
21.
Daskalos A, Oleksiewicz U, Filia A, Nikolaidis G, Xinarianos G, Gosney JR, Malliri A, Field JK, Liloglou T. UHRF1-mediated tumor suppressor gene inactivation in nonsmall cell lung cancer. Cancer. 2011;117:1027–37.
22.
Sadler KC, Krahn KN, Gaur NA, Ukomadu C. Liver growth in the embryo and during liver regeneration in zebrafish requires the cell cycle regulator, uhrf1. Proc Natl Acad Sci U S A. 2007;104:1570–5.CrossRefPubMedPubMedCentral
23.
Mousli M, Hopfner R, Abbady AQ, Monte D, Jeanblanc M, Oudet P, Louis B, Bronner C. ICBP90 belongs to a new family of proteins with an expression that is deregulated in cancer cells. Br J Cancer. 2003;89:120–7.
24.
Bonapace IM, Latella L, Papait R, Nicassio F, Sacco A, Muto M, Crescenzi M, Di Fiore PP. Np95 is regulated by E1A during mitotic reactivation of terminally differentiated cells and is essential for S phase entry. J Cell Biol. 2002;157:909–14.
25.
Tien AL, Senbanerjee S, Kulkarni A, Mudbhary R, Goudreau B, Ganesan S, Sadler KC, Ukomadu C. UHRF1 depletion causes a G2/M arrest, activation of DNA damage response and apoptosis. Biochem J. 2011;435:175–85.
Metadata
Title
UHRF1 gene silencing inhibits cell proliferation and promotes cell apoptosis in human cervical squamous cell carcinoma CaSki cells
Authors
Ting-Ting Ge
Meng Yang
Zhuo Chen
Ge Lou
Tao Gu
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2016
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-016-0253-8

Other articles of this Issue 1/2016

Journal of Ovarian Research 1/2016 Go to the issue

Research

High levels of pretreatment CA125 are associated to improved survival in high grade serous ovarian carcinoma

Research

Genome-wide transcriptional regulation of estrogen receptor targets in fallopian tube cells and the role of selective estrogen receptor modulators

Reviewer acknowledgement

Journal of Ovarian Research reviewer acknowledgement 2015

Research

Expression pattern of circadian genes and steroidogenesis-related genes after testosterone stimulation in the human ovary

Research

A centrosome clustering protein, KIFC1, predicts aggressive disease course in serous ovarian adenocarcinomas

Research

GnRH agonist triggering affects the kinetics of embryo development: a comparative study