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Aberrant promoter hypermethylation inhibits RGMA expression and contributes to tumor progression in breast cancer
by
Liu, Hai-Ting
, Ma, Ran-ran
, Song, Lin
, Li, Yan
, Wang, Ya-Wen
, Gao, Peng
, Tian, Ya-Ru
, Chen, Xu
, Zou, Yong-Xin
in
1-Phosphatidylinositol 3-kinase
/ 101/1
/ 13/1
/ 13/106
/ 13/109
/ 13/89
/ 13/95
/ 38/90
/ 45/22
/ 631/67/1347
/ 631/80/83
/ 64/60
/ AKT protein
/ Apoptosis
/ Breast cancer
/ Breast Neoplasms - genetics
/ Breast Neoplasms - pathology
/ Cell Biology
/ Cell growth
/ Cell Line, Tumor
/ Cell proliferation
/ Disease Progression
/ DNA methylation
/ DNA Methylation - genetics
/ DNMT1 protein
/ Female
/ GPI-Linked Proteins - metabolism
/ Human Genetics
/ Humans
/ Internal Medicine
/ Kinases
/ Medicine
/ Medicine & Public Health
/ Metastases
/ Nerve Tissue Proteins - metabolism
/ Oncology
/ Prognosis
/ Signal transduction
/ Therapeutic targets
/ Tumor suppressor genes
/ Tumorigenesis
2022
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Aberrant promoter hypermethylation inhibits RGMA expression and contributes to tumor progression in breast cancer
by
Liu, Hai-Ting
, Ma, Ran-ran
, Song, Lin
, Li, Yan
, Wang, Ya-Wen
, Gao, Peng
, Tian, Ya-Ru
, Chen, Xu
, Zou, Yong-Xin
in
1-Phosphatidylinositol 3-kinase
/ 101/1
/ 13/1
/ 13/106
/ 13/109
/ 13/89
/ 13/95
/ 38/90
/ 45/22
/ 631/67/1347
/ 631/80/83
/ 64/60
/ AKT protein
/ Apoptosis
/ Breast cancer
/ Breast Neoplasms - genetics
/ Breast Neoplasms - pathology
/ Cell Biology
/ Cell growth
/ Cell Line, Tumor
/ Cell proliferation
/ Disease Progression
/ DNA methylation
/ DNA Methylation - genetics
/ DNMT1 protein
/ Female
/ GPI-Linked Proteins - metabolism
/ Human Genetics
/ Humans
/ Internal Medicine
/ Kinases
/ Medicine
/ Medicine & Public Health
/ Metastases
/ Nerve Tissue Proteins - metabolism
/ Oncology
/ Prognosis
/ Signal transduction
/ Therapeutic targets
/ Tumor suppressor genes
/ Tumorigenesis
2022
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Aberrant promoter hypermethylation inhibits RGMA expression and contributes to tumor progression in breast cancer
by
Liu, Hai-Ting
, Ma, Ran-ran
, Song, Lin
, Li, Yan
, Wang, Ya-Wen
, Gao, Peng
, Tian, Ya-Ru
, Chen, Xu
, Zou, Yong-Xin
in
1-Phosphatidylinositol 3-kinase
/ 101/1
/ 13/1
/ 13/106
/ 13/109
/ 13/89
/ 13/95
/ 38/90
/ 45/22
/ 631/67/1347
/ 631/80/83
/ 64/60
/ AKT protein
/ Apoptosis
/ Breast cancer
/ Breast Neoplasms - genetics
/ Breast Neoplasms - pathology
/ Cell Biology
/ Cell growth
/ Cell Line, Tumor
/ Cell proliferation
/ Disease Progression
/ DNA methylation
/ DNA Methylation - genetics
/ DNMT1 protein
/ Female
/ GPI-Linked Proteins - metabolism
/ Human Genetics
/ Humans
/ Internal Medicine
/ Kinases
/ Medicine
/ Medicine & Public Health
/ Metastases
/ Nerve Tissue Proteins - metabolism
/ Oncology
/ Prognosis
/ Signal transduction
/ Therapeutic targets
/ Tumor suppressor genes
/ Tumorigenesis
2022
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Aberrant promoter hypermethylation inhibits RGMA expression and contributes to tumor progression in breast cancer
Journal Article
Aberrant promoter hypermethylation inhibits RGMA expression and contributes to tumor progression in breast cancer
2022
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Overview
Breast cancer (BC) is the most common cancer in women worldwide, and the exploration of aberrantly expressed genes might clarify tumorigenesis and help uncover new therapeutic strategies for BC. Although RGMA was recently recognized as a tumor suppressor gene, its detailed biological function and regulation in BC remain unclear. Herein, we found that RGMA was downregulated in BC tissues compared with non-tumorous breast tissues, particularly in metastatic BC samples, and that patients with low RGMA expression manifested a poorer prognosis. Furthermore, DNMT1 and DNMT3A were found to be recruited to the RGMA promoter and induced aberrant hypermethylation, resulting in downregulation of RGMA expression in BC. In contrast, RGMA overexpression suppressed BC cell proliferation and colony-formation capabilities and increased BC cell apoptosis. Furthermore, RGMA knockdown accelerated BC cell proliferation and suppressed cellular apoptosis in vitro and in vivo. Reversal of RGMA promoter methylation with 5-Aza-CdR restored RGMA expression and blocked tumor growth. Overall, DNMT1- and DNMT3A-mediated RGMA promoter hypermethylation led to downregulation of RGMA expression, and low RGMA expression contributed to BC growth via activation of the FAK/Src/PI3K/AKT-signaling pathway. Our data thus suggested that RGMA might be a promising therapeutic target in BC.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
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