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
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 5/2013

01-05-2013 | Translational Research and Biomarkers

Up-Regulation of miR-182 Expression after Epigenetic Modulation of Human Melanoma Cells

Authors: Suhu Liu, MD, PhD, Paul M. Howell, BS, Adam I. Riker, MD, FACS

Published in: Annals of Surgical Oncology | Issue 5/2013

Login to get access

Abstract

Purpose

We sought to investigate the epigenetic regulation of microRNAs (miRNAs) in melanoma.

Methods

We treated two highly metastatic human melanoma cell lines, C8161.9 and WM266-4, with the demethylating agents DAC (5-aza-2′-deoxycytidine) and trichostatin A. Locked nucleic acid–based miRNA expression profiling was utilized to examine the differential expression of miRNAs before and after treatment.

Results

We found that miR-182, a miRNA with oncogenic properties, was significantly up-regulated in human melanoma cells after epigenetic modulation. Genome sequence analysis revealed the presence of a prominent CpG island 8–10 kb upstream of mature miR-182. Methylation analysis showed that this genomic region was exclusively methylated in melanoma cells but not in human melanocytes, skin, or peripheral blood mononuclear cells.

Discussion

These results indicate that an epigenetic mechanism is likely involved in modulating the expression level of miR-182 in melanoma, and increased expression of oncogenic-like miR-182 could be a concern for melanoma patients after epigenetic therapy.
Appendix
Available only for authorised users
Literature
1.
2.
Balch CM, Buzaid AC, Atkins MB, et al. A new American Joint Committee on Cancer staging system for cutaneous melanoma. Cancer. 2000;88:1484–91.PubMedCrossRef
3.
Kagan J, Srivastava S, Barker PE, Belinsky SA, Cairns P. Towards clinical application of methylated DNA sequences as cancer biomarkers: a joint NCI’s EDRN and NIST workshop on standards, methods, assays, reagents and tools. Cancer Res. 2007;67:4545–9.PubMedCrossRef
4.
Mulero-Navarro S, Esteller M. Epigenetic biomarkers for human cancer: the time is now. Crit Rev Oncol Hematol. 2008;68:1–11.PubMedCrossRef
5.
Liu S, Ren S, Howell P, Fodstad O, Riker AI. Identification of novel epigenetically modified genes in human melanoma via promoter methylation gene profiling. Pigment Cell Melanoma Res. 2008;21:545–58.PubMedCrossRef
6.
Lodygin D, Tarasov V, Epanchintsev A, et al. Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell Cycle. 2008;7:2591–600.PubMedCrossRef
7.
Lujambio A, Calin GA, Villanueva A, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci USA. 2008;105:13556–61.PubMedCrossRef
8.
Fodstad O, Aamdal S, McMenamin M, Pihl A. A new experimental metastasis model in athymic nude mice, the human malignant melanoma lox. Int J Cancer. 1988;41:442–9.PubMedCrossRef
9.
Welch DR, Bisi JE, Miller BE, et al. Characterization of a highly invasive and spontaneously metastatic human malignant melanoma cell line. Int J Cancer. 1991;47:227–37.PubMedCrossRef
10.
Welch DR, Chen P, Miele ME, et al. Microcell-mediated transfer of chromosome 6 into metastatic human C8161 melanoma cells suppresses metastasis but does not inhibit tumorigenicity. Oncogene. 1994;9:255–62.PubMed
11.
Riker AI. Isolation and culture of melanoma cell lines. Methods Mol Med. 2004;88:93–9.PubMed
12.
Riker AI, Panelli MC, Kammula US, et al. Development and characterization of melanoma cell lines established by fine-needle aspiration biopsy: advances in the monitoring of patients with metastatic melanoma. Cancer Detect Prev. 1999;23:387–96.PubMedCrossRef
13.
Clark SJ, Harrison J, Paul CL, Frommer M. High sensitivity mapping of methylated cytosines. Nucleic Acids Res. 1994;22:2990–7.PubMedCrossRef
14.
Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA. 1996;93:9821–6.PubMedCrossRef
15.
Yegnasubramanian S, Kowalski J, Gonzalgo ML, et al. Hypermethylation of CpG islands in primary and metastatic human prostate cancer. Cancer Res. 2004;64:1975–86.PubMedCrossRef
16.
Takai D, Jones PA. The CpG island searcher: a new WWW resource. In Silico Biol. 2003;3:235–40.PubMed
17.
Segura MF, Hanniford D, Menendez S, et al. Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor. Proc Natl Acad Sci USA. 2009;106:1814–9.PubMedCrossRef
18.
Vaksman O, Stavnes HT, Kaern J, Trope CG, Davidson B, Reich R. miRNA profiling along tumor progression in ovarian carcinoma. J Cell Mol Med. 2010.
19.
Hannafon BN, Sebastiani P, de Las Morenas A, Lu J, Rosenberg CL. Expression of microRNA and their gene targets are dysregulated in preinvasive breast cancer. Breast Cancer Res. 2011;13:R24.PubMedCrossRef
20.
Moskwa P, Buffa FM, Pan Y, et al. miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors. Mol Cell. 2011;41:210–20.PubMedCrossRef
21.
Myatt SS, Wang J, Monteiro LJ, et al. Definition of microRNAs that repress expression of the tumor suppressor gene FOXO1 in endometrial cancer. Cancer Res. 2010;70:367–77.PubMedCrossRef
22.
Sarver AL, French AJ, Borralho PM, et al. Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states. BMC Cancer. 2009;9:401.PubMedCrossRef
23.
Schaefer A, Jung M, Mollenkopf HJ, et al. Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma. Int J Cancer. 2010;126:1166–76.PubMed
24.
Roa W, Brunet B, Guo L, et al. Identification of a new microRNA expression profile as a potential cancer screening tool. Clin Invest Med. 2010;33:E124.PubMed
25.
Jiang L, Mao P, Song L, et al. miR-182 as a prognostic marker for glioma progression and patient survival. Am J Pathol. 2010;177:29–38.PubMedCrossRef
26.
Bastian BC, LeBoit PE, Hamm H, Brocker EB, Pinkel D. Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization. Cancer Res. 1998;58:2170–5.PubMed
27.
Lin WM, Baker AC, Beroukhim R, et al. Modeling genomic diversity and tumor dependency in malignant melanoma. Cancer Res. 2008;68:664–73.PubMedCrossRef
28.
Sacheli R, Nguyen L, Borgs L, et al. Expression patterns of miR-96, miR-182 and miR-183 in the development inner ear. Gene Expr Patterns. 2009;9:364–70.PubMedCrossRef
29.
Stittrich AB, Haftmann C, Sgouroudis E, et al. The microRNA miR-182 is induced by IL-2 and promotes clonal expansion of activated helper T lymphocytes. Nat Immunol. 2010;11:1057–62.PubMedCrossRef
30.
Ormerod EJ, Everett CA, Hart IR. Enhanced experimental metastatic capacity of a human tumor line following treatment with 5-azacytidine. Cancer Res. 1986;46:884–90.PubMed
31.
Trainer DL, Kline T, Mallon F, Greig R, Poste G. Effect of 5-azacytidine on DNA methylation and the malignant properties of B16 melanoma cells. Cancer Res. 1985;45(12 Pt. 1):6124–30.
32.
Koh E, Bandle R, Clair T, Roberts DD, Stracke ML. Trichostatin A and 5-aza-2′-deoxycytidine switch S1P from an inhibitor to a stimulator of motility through pigenetic regulation of S1P receptors. Cancer Lett. 2007;250:53–62.PubMedCrossRef
Metadata
Title
Up-Regulation of miR-182 Expression after Epigenetic Modulation of Human Melanoma Cells
Authors
Suhu Liu, MD, PhD
Paul M. Howell, BS
Adam I. Riker, MD, FACS
Publication date
01-05-2013
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 5/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2467-3

Other articles of this Issue 5/2013

Annals of Surgical Oncology 5/2013 Go to the issue

Thoracic Oncology

Advantages of Diffusion-Weighted Imaging Over Positron Emission Tomography-Computed Tomography in Assessment of Hilar and Mediastinal Lymph Node in Lung Cancer

Endocrine Tumors

Comparative Outcomes of Laparoscopic and Open Adrenalectomy for Adrenocortical Carcinoma: Single, High-Volume Center Experience

Breast Oncology

Effect of MRI on the Management of Ductal Carcinoma In Situ of the Breast

Gastrointestinal Oncology

Perigastric Tumor Deposits in Primary Gastric Cancer: Implications for Patient Prognosis and Staging

Healthcare Policy and Outcomes

Validation of the Mexican Spanish Version of the EORTC QLQ-H&N35 Instrument to Measure Health-related Quality of Life in Patients with Head and Neck Cancers

Endocrine Tumors

Hereditary Medullary Thyroid Cancer: Age-Appropriate Thyroidectomy Improves Disease-Free Survival