RERG suppresses cell proliferation, migration and angiogenesis through ERK/NF-κB signaling pathway in nasopharyngeal carcinoma

Zhao, Weilin; Ma, Ning; Wang, Shumin; Mo, Yuchang; Zhang, Zhe; Huang, Guangwu; Midorikawa, Katsumi; Hiraku, Yusuke; Oikawa, Shinji; Murata, Mariko; Takeuchi, Kazuhiko

doi:10.1186/s13046-017-0554-9

Cited by 41 publications

(31 citation statements)

References 51 publications

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“…Additionally, the dual luciferase reporter assay validated that RERG was a target gene of miR-532-5p. In several cancer types, including breast cancer, RERG inhibits cell proliferation, migration, invasion and clonogenicity via the MAPK/ERK pathway (19,31). In the present study, cell proliferation and migration assays showed that RERG silencing could reverse miR-532-5p downregulation-induced cell proliferation and migration inhibition.…”

Section: Discussionsupporting

confidence: 56%

“…RERG was first identified as a ras-like, growth inhibitory protein induced by estrogen in breast cancer cells (18). Subsequent studies revealed that RERG was a negative regulator of multiple oncogenic pathways including the MAPK/ERK signaling in cancer cells (19,31). Furthermore, RERG was also regulated by histone deacetylases and miRNAs (19,32,33).…”

Section: Discussionmentioning

confidence: 99%

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miR‑532‑5p promotes breast cancer proliferation and migration by targeting RERG

et al. 2019

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Aberrant expression of microRNAs (miRNAs/miRs) mediates the initiation and progression of breast cancer. Therefore, it is important to investigate the molecular mechanisms of miRNAs and their effects on breast cancer progression. In the present study, miR-532-5p was highly expressed in breast cancer tissues compared with normal tissues. In addition, expression of ras-related and estrogen-regulated growth inhibitor (RERG), a tumor suppressor in breast cancer, was negatively correlated with miR-532-5p expression. Inhibition of miR-532-5p significantly elevated RERG at both mRNA and protein levels and inactivated the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. Overexpression of miR-532-5p decreased RERG expression and activated the MAPK/ERK signaling in breast cancer cell line MDA-MB-231. Bioinformatic analysis indicated that RERG 3'-untraslated region contained a putative binding site for miR-532-5p. Dual luciferase assay further validated RERG as a target gene of miR-532-5p. Notably, downregulation of miR-532-5p inhibited MDA-MB-231 cell proliferation and migration, which was partially attenuated upon RERG knockdown. In conclusion, the current study revealed an oncogenic role of miR-532-5p in breast cancer cells via direct targeting of RERG expression.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

miR‑532‑5p promotes breast cancer proliferation and migration by targeting RERG

et al. 2019

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“…46 Research has shown that the ectopic expression of RERG (Ras-like oestrogen-regulated growth inhibitor) in NPC cell lines resulted in a significant suppression of cell proliferation, invasion, and migration. 47 As a member of the RAS oncogene family, RAP2C has few reports on the development of cancer, which needs further study. Furthermore, MEF2C has recently been shown to play a role in the transcriptional control of cell cycle-related genes, and its degradation in mitosis contributes to G2/M checkpoint inactivation in growing myoblasts.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA expression in cervical cancer: Novel diagnostic and prognostic biomarkers

Gao

Zhou

Zhuang

et al. 2018

J of Cellular Biochemistry

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Growing evidence has shown that a large number of miRNAs are abnormally expressed in cervical cancer (CC) tissues and play irreplaceable roles in tumorigenesis, progression, and metastasis. This study aimed to identify new biomarkers and pivotal genes associated with CC prognosis through comprehensive bioinformatics analysis. At first, the data of gene expression microarray (GSE30656) was downloaded from GEO database and differential miRNAs were obtained. Additionally, 4 miRNAs associated with the survival time of patients with CC were screened through TCGA differential data analysis, Kaplan-Meier, and Landmark analysis. Among them, the low expression of miR-188 and high expression of miR-223 correlated with the short survival of CC patients, while the down-regulation of miR-99a and miR-125b was closely related to the 5-year survival rate of patients. Then, based on the correspondence between the differentially expressed genes (DEGs) in CC from the TCGA data and the 4 miRNAs target genes, 58 target genes were screened to perform the analysis of function enrichment and the visualization of protein-protein interaction (PPI) networks. The seven pivotal genes of the PPI network as the target genes of four miRNAs related to prognosis, they were directly or indirectly involved in the development of CC. In this study, based on high-throughput data mining, differentially expressed miRNAs and related target genes were analyzed to provide an effective bioinformatics basis for further understanding of the pathogenesis and prognosis of CC. And the results may be a promising biomarker for the early screening of high-risk populations and early diagnosis of cervical cancer.

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“…We also detected downregulation of RERG (RAS-like estrogen-regulated growth inhibitor) by DNA methylation in the cancer tissues. RERG-overexpressing cells showed significantly slower growth and less angiogenesis in tumor xenografts in nude mice [ 40 ]. DNA methylation occurs in Helicobacter pylori infection-related gastric cancer [ 41 , 42 ] and ulcerative colitis-associated colorectal cancer [ 43 ], indicating that DNA methylation is a key event of inflammation-related carcinogenesis.…”

Section: Epigenetic Alterations In Inflammation-related Carcinogenesimentioning

confidence: 99%

Inflammation and cancer

Murata

2018

Environ Health Prev Med

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450

283

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Infection and inflammation account for approximately 25% of cancer-causing factors. Inflammation-related cancers are characterized by mutagenic DNA lesions, such as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-nitroguanine. Our previous studies demonstrated the formation of 8-oxodG and 8-nitroguanine in the tissues of cancer and precancerous lesions due to infection (e.g., Opisthorchis viverrini-related cholangiocarcinoma, Schistosoma haematobium-associated bladder cancer, Helicobacter pylori-infected gastric cancer, human papillomavirus-related cervical cancer, Epstein-Barr virus-infected nasopharyngeal carcinoma) and pro-inflammatory factors (e.g., asbestos, nanomaterials, and inflammatory diseases such as Barrett’s esophagus and oral leukoplakia). Interestingly, several of our studies suggested that inflammation-associated DNA damage in cancer stem-like cells leads to cancer development with aggressive clinical features. Reactive oxygen/nitrogen species from inflammation damage not only DNA but also other biomacromolecules, such as proteins and lipids, resulting in their dysfunction. We identified oxidatively damaged proteins in cancer tissues by 2D Oxyblot followed by MALDI-TOF/TOF. As an example, oxidatively damaged transferrin released iron ion, which may mediate Fenton reactions and generate additional reactive oxygen species. Dysfunction of anti-oxidative proteins due to this damage might increase oxidative stress. Such damage in biomacromolecules may form a vicious cycle of oxidative stress, leading to cancer development. Epigenetic alterations such as DNA methylation and microRNA dysregulation play vital roles in carcinogenesis, especially in inflammation-related cancers. We examined epigenetic alterations, DNA methylation and microRNA dysregulation, in Epstein-Barr virus-related nasopharyngeal carcinoma in the endemic area of Southern China and found several differentially methylated tumor suppressor gene candidates by using a next-generation sequencer. Among these candidates, we revealed higher methylation rates of RAS-like estrogen-regulated growth inhibitor (RERG) in biopsy specimens of nasopharyngeal carcinoma more conveniently by using restriction enzyme-based real-time PCR. This result may help to improve cancer screening strategies. We profiled microRNAs of nasopharyngeal carcinoma tissues using microarrays. Quantitative RT-PCR analysis confirmed the concordant downregulation of miR-497 in cancer tissues and plasma, suggesting that plasma miR-497 could be used as a diagnostic biomarker for nasopharyngeal carcinoma. Chronic inflammation promotes genetic and epigenetic aberrations, with various pathogeneses. These changes may be useful biomarkers in liquid biopsy for early detection and prevention of cancer.

show abstract

RERG suppresses cell proliferation, migration and angiogenesis through ERK/NF-κB signaling pathway in nasopharyngeal carcinoma

Cited by 41 publications

References 51 publications

miR‑532‑5p promotes breast cancer proliferation and migration by targeting RERG

miR‑532‑5p promotes breast cancer proliferation and migration by targeting RERG

MicroRNA expression in cervical cancer: Novel diagnostic and prognostic biomarkers

Inflammation and cancer

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