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

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Tumor Biology
Published in: Tumor Biology 12/2014

01-12-2014 | Research Article

MiR-212 exerts suppressive effect on SKOV3 ovarian cancer cells through targeting HBEGF

Authors: Li-qiang Wei, Hui-tao Liang, Dong-chun Qin, Hui-fang Jin, Yong Zhao, Ming-cong She

Published in: Tumor Biology | Issue 12/2014

Login to get access

Abstract

MicroRNAs (miRNAs) play critical roles in the development and progression of ovarian cancer. We found that miR-212 was significantly downregulated in serum and tissues from epithelial ovarian cancer (EOC) patients. Overexpression of miR-212 in ovarian cancer cells inhibited cell proliferation, migration, and invasion. Luciferase reporter assay confirmed HBEGF as a direct target of miR-212. Overexpression of miR-212 decreased HBEGF expression at both the protein and messenger RNA (mRNA) levels. Knockdown of HBEGF expression in SKOV3 cell line significantly inhibited cell growth, migration, and invasion. HBEGF mRNA level was upregulated in EOC tissues and inversely correlated with miR-212 expression in tissues. Upregulation of HBEGF could attenuate the effect induced by miR-212. These findings indicate that miR-212 displays a tumor-suppressive effect in human ovarian cancer. And miR-212 suppresses cell proliferation, migration, and invasion by targeting the HBEGF transcript, highlighting the therapeutic potential of miR-212 and HBEGF in epithelial ovarian cancer treatment.
Literature
1.
Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.
2.
Marcus CS, Maxwell GL, Darcy KM, et al. Current approaches and challenges in managing and monitoring treatment response in ovarian cancer. J Cancer. 2014;5(1):25–30.CrossRef
3.
Shukla GC, Singh J, Barik S. MicroRNAs: processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol. 2011;3:83–92.PubMedPubMedCentral
4.
5.
Liang X, Zeng J, Wang L, Fang M, Wang Q, Zhao M, et al. Histone demethylase retinoblastoma binding protein 2 is overexpressed in hepatocellular carcinoma and negatively regulated by hsa-miR-212. PLoS ONE. 2013;8:e69784.CrossRef
6.
Jiping Z, Ming F, Lixiang W, Xiuming L, Yuqun S, Han Y, et al. MicroRNA-212 inhibits proliferation of gastric cancer by directly repressing retinoblastoma binding protein 2. J Cell Biochem. 2013;114:2666–72.CrossRef
7.
Meng X, Wu J, Pan C, Wang H, Ying X, Zhou Y, et al. Genetic and epigenetic down-regulation of microRNA-212 promotes colorectal tumor metastasis via dysregulation of MnSOD. Gastroenterology. 2013;145(2):426–36.CrossRef
8.
Sankaranarayanan R, Ferlay J. Worldwide burden of gynaecological cancer: the size of the problem. Best Pract Res Clin Obstet Gynaecol. 2006;20:207–25.CrossRef
9.
Li Y, Zhang D, Chen C, et al. MicroRNA-212 displays tumor-promoting properties in non-small cell lung cancer cells and targets the hedgehog pathway receptor PTCH1. Mol Biol Cell. 2012;23:1423–34.CrossRef
10.
Ma C, Nong K, Wu B, et al. miR-212 promotes pancreatic cancer cell growth and invasion by targeting the hedgehog signaling pathway receptor patched-1. J Exp Clin Cancer Res. 2014;33:54.CrossRef
11.
Higashiyama S, Abraham JA, Miller J, Fiddes JC, Klagsbrun M. A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF. Science. 1991;251:936–9.CrossRef
12.
Raab G, Higashiyama S, Hetelekidis S, et al. Biosynthesis and processing by phorbol ester of the cells surface-associated precursor form of heparin-binding EGF-like growth factor. Biochem Biophys Res Commun. 1994;204:592–7.CrossRef
13.
Higashiyama S, Lau K, Besner GE, et al. Structure of heparin-binding EGF-like growth factor. Multiple forms, primary structure, and glycosylation of the mature protein. J Biol Chem. 1992;267:6205–12.CrossRef
14.
Higashiyama S, Abraham JA, Klagsbrun M. Heparin-binding EGF-like growth factor stimulation of smooth muscle cell migration: dependence on interactions with cell surface heparan sulfate. J Cell Biol. 1993;122:933–40.CrossRef
15.
Marikovsky M, Breuing K, Liu PY, et al. Appearance of heparin-binding EGF-like growth factor in wound fluid as a response to injury. Proc Natl Acad Sci U S A. 1993;90:3889–93.CrossRef
16.
Hashimoto K, Higashiyama S, Asada H, et al. Heparin-binding epidermal growth factor-like growth factor is an autocrine growth factor for human keratinocytes. J Biol Chem. 1994;269:20060–6.CrossRef
17.
Peoples GE, Blotnick S, Takahashi K, et al. T lymphocytes that infiltrate tumors and atherosclerotic plaques produce heparin-binding epidermal growth factor-like growth factor and basic fibroblast growth factor: a potential pathologic role. Proc Natl Acad Sci U S A. 1995;92:6547–51.CrossRef
18.
Higashiyama S, Iwamoto R, Goishi K, et al. The membrane protein CD9/DRAP 27 potentiates the juxtacrine growth factor activity of the membrane-anchored heparin-binding EGF-like growth factor. J Cell Biol. 1995;128:929–38.CrossRef
19.
Iwamoto R, Higashiyama S, Mitamura T, et al. Heparin-binding EGF-like growth factor, which acts as the diphtheria toxin receptor, forms a complex with membrane protein DRAP27/CD9, which up-regulates functional receptors and diphtheria toxin sensitivity. EMBO J. 1994;13:2322–30.CrossRef
20.
Yotsumoto F, Yagi H, Suzuki SO, et al. Validation of HB-EGF and amphiregulin as targets for human cancer therapy. Biochem Biophys Res Commun. 2008;365(3):555–61.CrossRef
21.
Miyamoto S, Hirata M, Yamazaki A, et al. Heparin-binding EGF-like growth factor is a promising target for ovarian cancer therapy. Cancer Res. 2004;64:5720–7.CrossRef
22.
Ohnishi Y, Inoue H, Furukawa M, et al. Heparin-binding epidermal growth factor-like growth factor is a potent regulator of invasion activity in oral squamous cell carcinoma. Oncol Rep. 2012;27:954–8.CrossRef
23.
Haugen DR, Akslen LA, Varhaug JE, et al. Expression of c-erbB-3 and c-erbB-4 proteins in papillary thyroid carcinomas. Cancer Res. 1996;56:1184–8.PubMed
24.
Chandler LA, Sosnowski BA, McDonald JR, et al. Targeting tumor cells via EGF receptors: selective toxicity of an HBEGF-toxin fusion protein. Int J Cancer. 1998;78:106–11.CrossRef
25.
Ota I, Higashiyama S, Masui T, et al. Heparin-binding EGF-like growth factor enhances the activity of invasion and metastasis in thyroid cancer cells. Oncol Rep. 2013;30:1593–600.CrossRef
26.
Zhou Z N, Sharma V P, Beaty B T, et al. Autocrine HBEGF expression promotes breast cancer intravasation, metastasis and macrophage-independent invasion in vivo. Oncogene, 2013.
Metadata
Title
MiR-212 exerts suppressive effect on SKOV3 ovarian cancer cells through targeting HBEGF
Authors
Li-qiang Wei
Hui-tao Liang
Dong-chun Qin
Hui-fang Jin
Yong Zhao
Ming-cong She
Publication date
01-12-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 12/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2560-2

Other articles of this Issue 12/2014

Tumor Biology 12/2014 Go to the issue

Editorial

Letter regarding Meade et al. entitled “Models of acute mucosal tolerance to radiotherapy alone applied to synchronous chemo-radiation schedules in head and neck cancer”

Research Article

The ALDH7A1 genetic polymorphisms contribute to development of esophageal squamous cell carcinoma

Review

Genetic determinants of uveal melanoma

Research Article

Elucidation of caveolin 1 both as a tumor suppressor and metastasis promoter in light of epigenetic modulators

Research Article

A triterpenoid saponin from Adenophora triphylla var. japonica suppresses the growth of human gastric cancer cells via regulation of apoptosis and autophagy

Editorial

Letter regarding Shen et al. entitled “The APE1 Asp148Glu polymorphism and colorectal cancer susceptibility: a meta-analysis”
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