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
Cancer Cell International
Published in: Cancer Cell International 1/2016

Open Access 01-12-2016 | Primary Research

MiR-519d facilitates the progression and metastasis of cervical cancer through direct targeting Smad7

Authors: Jue-Yu Zhou, Si-Rong Zheng, Jie Liu, Rong Shi, Hai-Lang Yu, Min Wei

Published in: Cancer Cell International | Issue 1/2016

Login to get access

Abstract

Background

MicroRNAs (miRNAs) play pivotal roles in the development of various cancer types, including cervical cancer.

Methods and results

In this study, we showed that miR-519d, a miRNA within the chromosome 19 miRNA cluster, was significantly upregulated in cervical cancer tissues, compared with non-tumorous cervical samples. Suppression of miR-519d markedly attenuated the migration and invasion of HeLa and SiHa cervical cancer cells. Additionally, miR-519d inhibited the apoptosis of cervical cancer cells, and the proliferation of cervical cancer cells was also affected following transfection of miR-519d inhibitor. Moreover, we identified Smad7 to be a novel target of miR-519d in cervical cancer cells. MiR-519d matched the 3′-UTR of Smad7 mRNA. Transfection with miR-519d mimics led to apparent downregulation of Smad7 both at the mRNA and protein levels. Luciferase reporter analysis revealed that miR-519d reduced the luciferase activity of Smad7 mRNA 3′-UTR through matching site-dependent manner. And more notably, suppression of Smad7 remarkably restored the migration and invasion of miR-519d-depleted cervical cancer cells.

Conclusion

Taken together, these findings implicated that miR-519d promoted the progression and metastasis of cervical cancer through targeting Smad7.
Literature
1.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRefPubMed
2.
Wright JD, Huang Y, Ananth CV, et al. Influence of treatment center and hospital volume on survival for locally advanced cervical cancer. Gynecol Oncol. 2015;139:506–12.CrossRefPubMed
3.
Diaz-Padilla I, Monk BJ, Mackay HJ, Oaknin A. Treatment of metastatic cervical cancer: future directions involving targeted agents. Crit Rev Oncol Hematol. 2013;85:303–14.CrossRefPubMed
4.
Noordhuis MG, Fehrmann RS, Wisman GB, et al. Involvement of the TGF-beta and beta-catenin pathways in pelvic lymph node metastasis in early-stage cervical cancer. Clin Cancer Res. 2011;17:1317–30.CrossRefPubMed
5.
Hazelbag S, Kenter GG, Gorter A, Fleuren GJ. Prognostic relevance of TGF-beta1 and PAI-1 in cervical cancer. Int J Cancer. 2004;112:1020–8.CrossRefPubMed
6.
Javelaud D, Mohammad KS, McKenna CR, et al. Stable overexpression of Smad7 in human melanoma cells impairs bone metastasis. Cancer Res. 2007;67:2317–24.CrossRefPubMed
7.
Azuma H, Ehata S, Miyazaki H, et al. Effect of Smad7 expression on metastasis of mouse mammary carcinoma JygMC(A) cells. J Natl Cancer Inst. 2005;97:1734–46.CrossRefPubMed
8.
Hariharan R, Babu JM. P R, Pillai MR. Mutational analysis of Smad7 in human cervical cancer. Oncol Rep. 2009;21:1001–4.PubMed
9.
Inui M, Martello G, Piccolo S. MicroRNA control of signal transduction. Nat Rev Mol Cell Biol. 2010;11:252–63.CrossRefPubMed
10.
Baltimore D, Boldin MP, O’Connell RM, Rao DS, Taganov KD. MicroRNAs: new regulators of immune cell development and function. Nat Immunol. 2008;9:839–45.CrossRefPubMed
11.
12.
Asangani IA, Rasheed SA, Nikolova DA, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 2008;27:2128–36.CrossRefPubMed
13.
14.
Zhang JG, Wang JJ, Zhao F, Liu Q, Jiang K, Yang GH. MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC). Clin Chim Acta. 2010;411:846–52.CrossRefPubMed
15.
Fornari F, Milazzo M, Chieco P, et al. In hepatocellular carcinoma miR-519d is up-regulated by p53 and DNA hypomethylation and targets CDKN1A/p21, PTEN, AKT3 and TIMP2. J Pathol. 2012;227:275–85.CrossRefPubMed
16.
17.
Wan C, Hou S, Ni R, et al. MIF4G domain containing protein regulates cell cycle and hepatic carcinogenesis by antagonizing CDK2-dependent p27 stability. Oncogene. 2015;34:237–45.CrossRefPubMed
18.
Tsai HC, Su HL, Huang CY, Fong YC, Hsu CJ, Tang CH. CTGF increases matrix metalloproteinases expression and subsequently promotes tumor metastasis in human osteosarcoma through down-regulating miR-519d. Oncotarget. 2014;5:3800–12.CrossRefPubMedPubMedCentral
19.
Wang X, Tang S, Le SY, et al. Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One. 2008;3:e2557.CrossRefPubMedPubMedCentral
20.
Luo L, Li N, Lv N, Huang D. SMAD7: a timer of tumor progression targeting TGF-β signaling. Tumour Biol. 2014;35(9):8379–85.CrossRefPubMed
21.
Altomare D, Velidandla R, Pirisi L, Creek KE. Partial loss of Smad signaling during in vitro progression of HPV16-immortalized human keratinocytes. BMC Cancer. 2013;13:424.CrossRefPubMedPubMedCentral
22.
Hou YY, Cao WW, Li L, et al. MicroRNA-519d targets MKi67 and suppresses cell growth in the hepatocellular carcinoma cell line QGY-7703. Cancer Lett. 2011;307:182–90.CrossRefPubMed
23.
24.
Valera VA, Walter BA, Linehan WM, Merino MJ. Regulatory effects of microRNA-92 (miR-92) on VHL gene expression and the hypoxic activation of miR-210 in clear cell renal cell carcinoma. J Cancer. 2011;2:515–26.CrossRefPubMedPubMedCentral
25.
Corcoran C, Friel AM, Duffy MJ, Crown J, O’Driscoll L. Intracellular and extracellular microRNAs in breast cancer. Clin Chem. 2011;57:18–32.CrossRefPubMed
26.
Shrestha S, Hsu SD, Huang WY, et al. A systematic review of microRNA expression profiling studies in human gastric cancer. Cancer Med. 2014;3:878–88.CrossRefPubMedPubMedCentral
27.
Pang Y, Mao H, Shen L, Zhao Z, Liu R, Liu P. MiR-519d represses ovarian cancer cell proliferation and enhances cisplatin-mediated cytotoxicity in vitro by targeting XIAP. Onco Targets Ther. 2014;7:587–97.CrossRefPubMedPubMedCentral
28.
Tsai CS, Lai CH, Wang CC, et al. The prognostic factors for patients with early cervical cancer treated by radical hysterectomy and postoperative radiotherapy. Gynecol Oncol. 1999;75:328–33.CrossRefPubMed
29.
30.
Nagura M, Matsumura N, Baba T, et al. Invasion of uterine cervical squamous cell carcinoma cells is facilitated by locoregional interaction with cancer-associated fibroblasts via activating transforming growth factor-beta. Gynecol Oncol. 2015;136:104–11.CrossRefPubMed
31.
Nakao A, Afrakhte M, Moren A, et al. Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature. 1997;389:631–5.CrossRefPubMed
32.
Wang P, Fan J, Chen Z, et al. Low-level expression of Smad7 correlates with lymph node metastasis and poor prognosis in patients with pancreatic cancer. Ann Surg Oncol. 2009;16:826–35.CrossRefPubMed
33.
Zhu Z, Xu Y, Zhao J, et al. miR-367 promotes epithelial-to-mesenchymal transition and invasion of pancreatic ductal adenocarcinoma cells by targeting the Smad7-TGF-beta signalling pathway. Br J Cancer. 2015;112:1367–75.CrossRefPubMed
34.
Kan H, Guo W, Huang Y, Liu D. MicroRNA-520g induces epithelial-mesenchymal transition and promotes metastasis of hepatocellular carcinoma by targeting SMAD7. FEBS Lett. 2015;589:102–9.CrossRefPubMed
35.
Li Y, Wang H, Li J, Yue W. MiR-181c modulates the proliferation, migration, and invasion of neuroblastoma cells by targeting Smad7. Acta Biochim Biophys Sin (Shanghai). 2014;46:48–55.CrossRef
36.
Metadata
Title
MiR-519d facilitates the progression and metastasis of cervical cancer through direct targeting Smad7
Authors
Jue-Yu Zhou
Si-Rong Zheng
Jie Liu
Rong Shi
Hai-Lang Yu
Min Wei
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2016
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-016-0298-1

Other articles of this Issue 1/2016

Cancer Cell International 1/2016 Go to the issue

Hypothesis

Endogenous electromagnetic forces emissions during cell respiration as additional factor in cancer origin

Primary research

Relationship between TRAF6 and deterioration of HCC: an immunohistochemical and in vitro study

Primary research

A microalga, Euglena tuba induces apoptosis and suppresses metastasis in human lung and breast carcinoma cells through ROS-mediated regulation of MAPKs

Primary research

Influence of TP53 and CDH1 genes in hepatocellular cancer spheroid formation and culture: a model system to understand cancer cell growth mechanics

Primary research

Alpha-synuclein contributes to malignant progression of human meningioma via the Akt/mTOR pathway

Primary research

Success of tumorsphere isolation from WHO grade IV gliomas does not correlate with the weight of fresh tumor specimens: an immunohistochemical characterization of tumorsphere differentiation
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