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
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2020

01-12-2020 | Ovarian Cancer | Primary research

Cyclin H predicts the poor prognosis and promotes the proliferation of ovarian cancer

Authors: Chen Peng, Yansong Yang, Li Ji, Panpan Yang, Xiaoqing Yang, Yuquan Zhang

Published in: Cancer Cell International | Issue 1/2020

Login to get access

Abstract

Background

Cell cycle dysregulation plays a key role in the pathogenesis of malignant tumors. As a part of the CDK-activating kinase (CAK) trimeric complex, cyclin H is necessary to regulate the cell cycle and proliferation. This investigation aims to characterize the clinical significance and the biological functions of cyclin H in ovarian cancer.

Methods

Immunohistochemical staining was performed on 60 ovarian cancer cases, and a correlation between cyclin H expression and the clinical characteristics of ovarian cancer was analyzed. The function of cyclin H in ovarian cancer was further explored using HO8910 cells and a subcutaneous xenograft model of nude mice.

Result

Cyclin H was slightly expressed in grade 1 ovarian cancer but highly expressed in grade 2 and grade 3 cancerous tissues. The Spearman’s rank correlation analysis showed that the expression of cyclin H is positively correlated with the tumor grade, the FIGO stage, histological grade, and the peritoneal metastasis of ovarian cancer and is also positively correlated with the Ki67 and p-CDK2 in ovarian cancer. Additionally, we found that the five-year survival rate was higher in patients expressing low cyclin H than those expressing high cyclin H. Further, knockdown of cyclin H was achieved using an shRNA in HO8910 ovarian cancer cell line. Silencing cyclin H resulted in a G1/S cell cycle arrest in ovarian cancer cells suppressing its growth. The Ki67 expression was also decreased in cyclin H silenced ovarian cancer.

Conclusion

These results suggest that high expression of cyclin H predicts the poor prognosis and promotes the growth of ovarian cancer by regulating the cell cycle.
Appendix
Available only for authorised users
Literature
1.
Herzog TJ, Pothuri B. Ovarian cancer: a focus on management of recurrent disease. Nat Clin Pract Oncol. 2006;3(11):604–11.PubMedCrossRef
2.
Webb PM, Jordan SJ. Epidemiology of epithelial ovarian cancer. Best Pract Res Clin Obstet Gynaecol. 2017;41:3–14.PubMedCrossRef
3.
4.
Kossai M, Leary A, Scoazec JY, Genestie C. Ovarian cancer: a heterogeneous disease. Pathobiology. 2018;85(1–2):41–9.PubMedCrossRef
5.
Doubeni CA, Doubeni AR, Myers AE. Diagnosis and management of ovarian cancer. Am Fam Physician. 2016;93(11):937–44.PubMed
6.
Stewart C, Ralyea C, Lockwood S. Ovarian cancer: an integrated review. Semin Oncol Nurs. 2019;35(2):151–6.PubMedCrossRef
7.
8.
9.
10.
11.
Patel H, Abduljabbar R, Lai CF, Periyasamy M, Harrod A, Gemma C, Steel JH, Patel N, Busonero C, Jerjees D, et al. Expression of CDK7, Cyclin H, and MAT1 is elevated in breast cancer and is prognostic in estrogen receptor-positive breast cancer. Clin Cancer Res. 2016;22(23):5929–38.PubMedPubMedCentralCrossRef
12.
Zhang J, Yang X, Wang Y, Shi H, Guan C, Yao L, Huang X, Ding Z, Huang Y, Wang H, et al. Low expression of cyclinH and cyclin-dependent kinase 7 can decrease the proliferation of human esophageal squamous cell carcinoma. Dig Dis Sci. 2013;58(7):2028–37.PubMedCrossRef
13.
Kayaselcuk F, Erkanli S, Bolat F, Seydaoglu G, Kuscu E, Demirhan B. Expression of cyclin H in normal and cancerous endometrium, its correlation with other cyclins, and association with clinicopathologic parameters. Int J Gynecol Cancer. 2006;16(1):402–8.PubMedCrossRef
14.
Dorn J, Spatz H, Schmieder M, Barth TF, Blatz A, Henne-Bruns D, Knippschild U, Kramer K. Cyclin H expression is increased in GIST with very-high risk of malignancy. BMC Cancer. 2010;10:350.PubMedPubMedCentralCrossRef
15.
Schneider E, Kartarius S, Schuster N, Montenarh M. The cyclin H/cdk7/Mat1 kinase activity is regulated by CK2 phosphorylation of cyclin H. Oncogene. 2002;21(33):5031–7.PubMedCrossRef
16.
Jiang X, Tang H, Chen T. Epidemiology of gynecologic cancers in China. J Gynecol Oncol. 2018;29(1):e7.PubMedCrossRef
17.
Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.PubMedCrossRef
18.
Pozzar RA, Berry DL. Patient-centered research priorities in ovarian cancer: a systematic review of potential determinants of guideline care. Gynecol Oncol. 2017;147(3):714–22.PubMedCrossRef
19.
Karakashev S, Aird KM. Ovarian cancer: how can resistance to chemotherapy be tackled? Future Oncol. 2017;13(30):2737–9.PubMedCrossRef
20.
21.
Larochelle S, Chen J, Knights R, Pandur J, Morcillo P, Erdjument-Bromage H, Tempst P, Suter B, Fisher RP. T-loop phosphorylation stabilizes the CDK7-cyclin H-MAT1 complex in vivo and regulates its CTD kinase activity. EMBO J. 2001;20(14):3749–59.PubMedPubMedCentralCrossRef
22.
Fuss JO, Tainer JA. XPB and XPD helicases in TFIIH orchestrate DNA duplex opening and damage verification to coordinate repair with transcription and cell cycle via CAK kinase. DNA Repair (Amst). 2011;10(7):697–713.PubMedPubMedCentralCrossRef
23.
Shiekhattar R, Mermelstein F, Fisher RP, Drapkin R, Dynlacht B, Wessling HC, Morgan DO, Reinberg D. Cdk-activating kinase complex is a component of human transcription factor TFIIH. Nature. 1995;374(6519):283–7.PubMedCrossRef
24.
25.
Palugulla S, Devaraju P, Kayal S, Narayan SK, Mathaiyan J. Genetic polymorphisms in cyclin H gene are associated with oxaliplatin-induced acute peripheral neuropathy in South Indian digestive tract cancer patients. Cancer Chemother Pharmacol. 2018;82(3):421–8.PubMedCrossRef
26.
Murali A, Nalinakumari KR, Thomas S, Kannan S. Association of single nucleotide polymorphisms in cell cycle regulatory genes with oral cancer susceptibility. Br J Oral Maxillofac Surg. 2014;52(7):652–8.PubMedCrossRef
27.
Bavi P, Abubaker J, Hussain A, Sultana M, Al-Dayel F, Uddin S, Al-Kuraya KS. Reduced or absent cyclin H expression is an independent prognostic marker for poor outcome in diffuse large B-cell lymphoma. Hum Pathol. 2008;39(6):885–94.PubMedCrossRef
28.
Liu M, Liu H, Chen J. Mechanisms of the CDK4/6 inhibitor palbociclib (PD 0332991) and its future application in cancer treatment (Review). Oncol Rep. 2018;39(3):901–11.PubMed
29.
Dai QS, Liu W, Wang XB, Lu N, Gong DD, Kong LY, Guo QL. NCPMF-60 induces G2/M cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. Anticancer Drugs. 2011;22(1):46–57.PubMedCrossRef
30.
Sanchez-Martinez C, Lallena MJ, Sanfeliciano SG, de Dios A. Cyclin dependent kinase (CDK) inhibitors as anticancer drugs: recent advances (2015–2019). Bioorg Med Chem Lett. 2019;29(20):126637.PubMedCrossRef
31.
Diaz-Moralli S, Tarrado-Castellarnau M, Miranda A, Cascante M. Targeting cell cycle regulation in cancer therapy. Pharmacol Ther. 2013;138(2):255–71.PubMedCrossRef
Metadata
Title
Cyclin H predicts the poor prognosis and promotes the proliferation of ovarian cancer
Authors
Chen Peng
Yansong Yang
Li Ji
Panpan Yang
Xiaoqing Yang
Yuquan Zhang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01406-5

Other articles of this Issue 1/2020

Cancer Cell International 1/2020 Go to the issue

Primary research

ALKBH5-mediated m6A demethylation of lncRNA PVT1 plays an oncogenic role in osteosarcoma

Primary research

CAFs affect the proliferation and treatment response of head and neck cancer spheroids during co-culturing in a unique in vitro model

Review

Autophagy regulation using luteolin: new insight into its anti-tumor activity

Primary research

CircRNA CDR1as/miR-641/HOXA9 pathway regulated stemness contributes to cisplatin resistance in non-small cell lung cancer (NSCLC)

Primary research

MicroRNA-93-5p promotes epithelial-mesenchymal transition in gastric cancer by repressing tumor suppressor AHNAK expression

Primary research

β-catenin promotes MTX resistance of leukemia cells by down-regulating FPGS expression via NF-κB
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits