Regulation of RUNX3 tumor suppressor gene expressionin cutaneous melanoma

Minoru Kitago, Steve R. Martinez, Takeshi Nakamura, Myung Shin Sim, Dave S B Hoon

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Purpose: RUNX3 is a known tumor suppressor gene in several carcinomas. Aberration in RUNX3 expression has not been described for cutaneous melanoma. Therefore, we assessed the expression of RUNX3 in cutaneous melanoma and its regulatory mechanisms relative to tumor progression. Experimental Design: The expression of RUNX3 mRNA and miR-532-5p (microRNA) was assessed in melanoma lines and in primary and metastatic melanoma tumors. Results: RUNX3 mRNA expression was down-regulated in 11 of 11 (100%) metastatic melanoma lines relative to normal melanocytes (P < 0.001). Among 123 primary and metastatic melanoma tumors and 12 normal skin samples, RUNX3 expression was significantly down-regulated in primary melanomas (n = 82; P = 0.02) and in melanoma metastasis (n = 41; P < 0.0001) versus normal skin (n = 12). This suggested that RUNX3 down-regulation may play a role in the development and progression of melanoma. RUNX3 promoter region hypermethylation was assessed as a possible regulator of RUNX3 expression using methylation-specific PCR. Assessment of RUNX3 promoter region methylation showed that only 5 of 17 (29%) melanoma lines, 2 of 52 (4%) primary melanomas, and 5 of 30 (17%) metastatic melanomas had hypermethylation of the promoter region. A microRNA (miR-532-5p) was identified as a target of RUNX3 mRNA sequences. miR-532-5p expression was shown to be significantly up-regulated in melanoma lines and metastatic melanoma tumors relative to normal melanocytes and primary melanomas, respectively. To investigate the relation between RUNX3 and miR-532-5p, anti -miR-532-5p was transfected into melanoma lines. Inhibition of miR-532-5p up-regulated both RUNX3 mRNA and protein expression. Conclusions: RUNX3 is down-regulated during melanoma progression and miR-532-5p is a regulatory factor of RUNX3 expression.

Original languageEnglish (US)
Pages (from-to)2988-2994
Number of pages7
JournalClinical Cancer Research
Volume15
Issue number9
DOIs
StatePublished - May 1 2009
Externally publishedYes

Fingerprint

Tumor Suppressor Genes
Melanoma
Skin
Genetic Promoter Regions
Messenger RNA
Melanocytes
MicroRNAs
Methylation
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kitago, M., Martinez, S. R., Nakamura, T., Sim, M. S., & Hoon, D. S. B. (2009). Regulation of RUNX3 tumor suppressor gene expressionin cutaneous melanoma. Clinical Cancer Research, 15(9), 2988-2994. https://doi.org/10.1158/1078-0432.CCR-08-3172

Regulation of RUNX3 tumor suppressor gene expressionin cutaneous melanoma. / Kitago, Minoru; Martinez, Steve R.; Nakamura, Takeshi; Sim, Myung Shin; Hoon, Dave S B.

In: Clinical Cancer Research, Vol. 15, No. 9, 01.05.2009, p. 2988-2994.

Research output: Contribution to journalArticle

Kitago, M, Martinez, SR, Nakamura, T, Sim, MS & Hoon, DSB 2009, 'Regulation of RUNX3 tumor suppressor gene expressionin cutaneous melanoma', Clinical Cancer Research, vol. 15, no. 9, pp. 2988-2994. https://doi.org/10.1158/1078-0432.CCR-08-3172
Kitago, Minoru ; Martinez, Steve R. ; Nakamura, Takeshi ; Sim, Myung Shin ; Hoon, Dave S B. / Regulation of RUNX3 tumor suppressor gene expressionin cutaneous melanoma. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 9. pp. 2988-2994.
@article{44283fb46777495cb567f4b6901ef6cc,
title = "Regulation of RUNX3 tumor suppressor gene expressionin cutaneous melanoma",
abstract = "Purpose: RUNX3 is a known tumor suppressor gene in several carcinomas. Aberration in RUNX3 expression has not been described for cutaneous melanoma. Therefore, we assessed the expression of RUNX3 in cutaneous melanoma and its regulatory mechanisms relative to tumor progression. Experimental Design: The expression of RUNX3 mRNA and miR-532-5p (microRNA) was assessed in melanoma lines and in primary and metastatic melanoma tumors. Results: RUNX3 mRNA expression was down-regulated in 11 of 11 (100{\%}) metastatic melanoma lines relative to normal melanocytes (P < 0.001). Among 123 primary and metastatic melanoma tumors and 12 normal skin samples, RUNX3 expression was significantly down-regulated in primary melanomas (n = 82; P = 0.02) and in melanoma metastasis (n = 41; P < 0.0001) versus normal skin (n = 12). This suggested that RUNX3 down-regulation may play a role in the development and progression of melanoma. RUNX3 promoter region hypermethylation was assessed as a possible regulator of RUNX3 expression using methylation-specific PCR. Assessment of RUNX3 promoter region methylation showed that only 5 of 17 (29{\%}) melanoma lines, 2 of 52 (4{\%}) primary melanomas, and 5 of 30 (17{\%}) metastatic melanomas had hypermethylation of the promoter region. A microRNA (miR-532-5p) was identified as a target of RUNX3 mRNA sequences. miR-532-5p expression was shown to be significantly up-regulated in melanoma lines and metastatic melanoma tumors relative to normal melanocytes and primary melanomas, respectively. To investigate the relation between RUNX3 and miR-532-5p, anti -miR-532-5p was transfected into melanoma lines. Inhibition of miR-532-5p up-regulated both RUNX3 mRNA and protein expression. Conclusions: RUNX3 is down-regulated during melanoma progression and miR-532-5p is a regulatory factor of RUNX3 expression.",
author = "Minoru Kitago and Martinez, {Steve R.} and Takeshi Nakamura and Sim, {Myung Shin} and Hoon, {Dave S B}",
year = "2009",
month = "5",
day = "1",
doi = "10.1158/1078-0432.CCR-08-3172",
language = "English (US)",
volume = "15",
pages = "2988--2994",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "9",

}

TY - JOUR

T1 - Regulation of RUNX3 tumor suppressor gene expressionin cutaneous melanoma

AU - Kitago, Minoru

AU - Martinez, Steve R.

AU - Nakamura, Takeshi

AU - Sim, Myung Shin

AU - Hoon, Dave S B

PY - 2009/5/1

Y1 - 2009/5/1

N2 - Purpose: RUNX3 is a known tumor suppressor gene in several carcinomas. Aberration in RUNX3 expression has not been described for cutaneous melanoma. Therefore, we assessed the expression of RUNX3 in cutaneous melanoma and its regulatory mechanisms relative to tumor progression. Experimental Design: The expression of RUNX3 mRNA and miR-532-5p (microRNA) was assessed in melanoma lines and in primary and metastatic melanoma tumors. Results: RUNX3 mRNA expression was down-regulated in 11 of 11 (100%) metastatic melanoma lines relative to normal melanocytes (P < 0.001). Among 123 primary and metastatic melanoma tumors and 12 normal skin samples, RUNX3 expression was significantly down-regulated in primary melanomas (n = 82; P = 0.02) and in melanoma metastasis (n = 41; P < 0.0001) versus normal skin (n = 12). This suggested that RUNX3 down-regulation may play a role in the development and progression of melanoma. RUNX3 promoter region hypermethylation was assessed as a possible regulator of RUNX3 expression using methylation-specific PCR. Assessment of RUNX3 promoter region methylation showed that only 5 of 17 (29%) melanoma lines, 2 of 52 (4%) primary melanomas, and 5 of 30 (17%) metastatic melanomas had hypermethylation of the promoter region. A microRNA (miR-532-5p) was identified as a target of RUNX3 mRNA sequences. miR-532-5p expression was shown to be significantly up-regulated in melanoma lines and metastatic melanoma tumors relative to normal melanocytes and primary melanomas, respectively. To investigate the relation between RUNX3 and miR-532-5p, anti -miR-532-5p was transfected into melanoma lines. Inhibition of miR-532-5p up-regulated both RUNX3 mRNA and protein expression. Conclusions: RUNX3 is down-regulated during melanoma progression and miR-532-5p is a regulatory factor of RUNX3 expression.

AB - Purpose: RUNX3 is a known tumor suppressor gene in several carcinomas. Aberration in RUNX3 expression has not been described for cutaneous melanoma. Therefore, we assessed the expression of RUNX3 in cutaneous melanoma and its regulatory mechanisms relative to tumor progression. Experimental Design: The expression of RUNX3 mRNA and miR-532-5p (microRNA) was assessed in melanoma lines and in primary and metastatic melanoma tumors. Results: RUNX3 mRNA expression was down-regulated in 11 of 11 (100%) metastatic melanoma lines relative to normal melanocytes (P < 0.001). Among 123 primary and metastatic melanoma tumors and 12 normal skin samples, RUNX3 expression was significantly down-regulated in primary melanomas (n = 82; P = 0.02) and in melanoma metastasis (n = 41; P < 0.0001) versus normal skin (n = 12). This suggested that RUNX3 down-regulation may play a role in the development and progression of melanoma. RUNX3 promoter region hypermethylation was assessed as a possible regulator of RUNX3 expression using methylation-specific PCR. Assessment of RUNX3 promoter region methylation showed that only 5 of 17 (29%) melanoma lines, 2 of 52 (4%) primary melanomas, and 5 of 30 (17%) metastatic melanomas had hypermethylation of the promoter region. A microRNA (miR-532-5p) was identified as a target of RUNX3 mRNA sequences. miR-532-5p expression was shown to be significantly up-regulated in melanoma lines and metastatic melanoma tumors relative to normal melanocytes and primary melanomas, respectively. To investigate the relation between RUNX3 and miR-532-5p, anti -miR-532-5p was transfected into melanoma lines. Inhibition of miR-532-5p up-regulated both RUNX3 mRNA and protein expression. Conclusions: RUNX3 is down-regulated during melanoma progression and miR-532-5p is a regulatory factor of RUNX3 expression.

UR - http://www.scopus.com/inward/record.url?scp=65649092616&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65649092616&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-08-3172

DO - 10.1158/1078-0432.CCR-08-3172

M3 - Article

VL - 15

SP - 2988

EP - 2994

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 9

ER -