MRGD, a MAS-related G-protein Coupled Receptor, Promotes Tumorigenisis and Is Highly Expressed in Lung Cancer

Nishimura, Syoyo; Uno, Masashi; Kaneta, Yasuyuki; Fukuchi, Kenji; Nishigohri, Haruyuki; Hasegawa, Jun; Komori, Hironobu; Takeda, Shigeki; Enomoto, Katsuhiko; Nara, Futoshi; Agatsuma, Toshinori

doi:10.1371/journal.pone.0038618

Cited by 18 publications

(26 citation statements)

References 23 publications

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“…Furthermore, recent data suggested a proliferative role for MrgD, which in contrast to what has been proposed in the past, 29 is not expressed exclusively in nociceptive sensory neurons 21,29,30 (Online Figure V). However, we could not find any evidence for proliferative or antiproliferative activity of alamandine and of β-alanine in 2 different human tumoral cell lines, which also express MrgD (Online Figure IIA-IIB).…”

Section: Ace2mentioning

confidence: 61%

Discovery and Characterization of Alamandine

Lautner¹,

Villela²,

Fraga‐Silva³

et al. 2013

Circulation Research

336

266

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n the past few years, novel components of the renin-angiotensin system (RAS) have been described, including the prorenin/ renin receptor, 1 angiotensin-converting enzyme-2 (ACE2), 2,3 and Mas.4 ACE2 and Mas are now considered to be part of a novel axis of the RAS, the ACE2/angiotensin 1 to 7 [Ang-(1-7)]/Mas axis, 4-11 which counteracts most of the action of the classical Rationale: The renin-angiotensin system (RAS) is a key regulator of the cardiovascular system, electrolyte, and water balance. Here, we report identification and characterization of alamandine, a new heptapeptide generated by catalytic action of angiotensin-converting enzyme-2 angiotensin A or directly from angiotensin-(1-7).Objective: To characterize a novel component of the RAS, alamandine. Methods and Results:Using mass spectrometry we observed that alamandine circulates in human blood and can be formed from angiotensin-(1-7) in the heart. Alamandine produces several physiological actions that resemble those produced by angiotensin-(1-7), including vasodilation, antifibrosis, antihypertensive, and central effects. Key Words: angiotensin II ■ antihypertensive treatment ■ cardiovascular system ■ hypertension ■ renin-angiotensin system ■ vasoactive peptides ■ vascular reactivity Original received February 7, 2013; revision received February 22, 2013; accepted February 27, 2013. In January 2013, the average time from submission to first decision for all original research papers submitted to Circulation Research was 12.2 days.Brief UltraRapid Communications are designed to be a format for manuscripts that are of outstanding interest to the readership, report definitive observations, but have a relatively narrow scope. Less comprehensive than Regular Articles but still scientifically rigorous, BURCs present seminal findings that have the potential to open up new avenues of research. A decision on BURCs is rendered within 7 days of submission.From the

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Section: Ace2mentioning

confidence: 61%

Discovery and Characterization of Alamandine

Lautner¹,

Villela²,

Fraga‐Silva³

et al. 2013

Circulation Research

336

266

View full text Add to dashboard Cite

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“…Other Mrgprs are overexpressed in tumors, such as hMRGPRD, and the expression of hMRGPRD, hMRGPRX1, and hMRGPRX4 as well as of rhesus monkey MRGPRX genes elicit hyperproliferation in transfected cells, most likely by their strong constitutive activity (Andrawis et al, 1992;Burstein et al, 2006;Nishimura et al, 2012). Similar effects are described from Mrgpr-overexpressing transgenic animals ( Table 2).…”

Section: Mas-related G Protein-coupled Receptors In Tumorsmentioning

confidence: 59%

Mas and Its Related G Protein–Coupled Receptors, Mrgprs

et al. 2014

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“…Significant functional groups found using lung tissue genes include the G-protein coupled receptor signaling pathway (GO:0007187) and the regulation of MAPK cascade (GO:0043408). The G protein-coupled receptor is known to promote tumorigenesis and is highly expressed in lung cancer [ 95 ]. Overexpression of G protein-coupled receptors is known to correlate with poorer tumor differentiation and higher tumor proliferation in non-small-cell lung cancer [ 96 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of potential tissue-specific cancer biomarkers and development of cancer versus normal genomic classifiers

et al. 2017

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Machine learning techniques for cancer prediction and biomarker discovery can hasten cancer detection and significantly improve prognosis. Recent “OMICS” studies which include a variety of cancer and normal tissue samples along with machine learning approaches have the potential to further accelerate such discovery. To demonstrate this potential, 2,175 gene expression samples from nine tissue types were obtained to identify gene sets whose expression is characteristic of each cancer class. Using random forests classification and ten-fold cross-validation, we developed nine single-tissue classifiers, two multi-tissue cancer-versus-normal classifiers, and one multi-tissue normal classifier. Given a sample of a specified tissue type, the single-tissue models classified samples as cancer or normal with a testing accuracy between 85.29% and 100%. Given a sample of non-specific tissue type, the multi-tissue bi-class model classified the sample as cancer versus normal with a testing accuracy of 97.89%. Given a sample of non-specific tissue type, the multi-tissue multi-class model classified the sample as cancer versus normal and as a specific tissue type with a testing accuracy of 97.43%. Given a normal sample of any of the nine tissue types, the multi-tissue normal model classified the sample as a particular tissue type with a testing accuracy of 97.35%. The machine learning classifiers developed in this study identify potential cancer biomarkers with sensitivity and specificity that exceed those of existing biomarkers and pointed to pathways that are critical to tissue-specific tumor development. This study demonstrates the feasibility of predicting the tissue origin of carcinoma in the context of multiple cancer classes.

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MRGD, a MAS-related G-protein Coupled Receptor, Promotes Tumorigenisis and Is Highly Expressed in Lung Cancer

Cited by 18 publications

References 23 publications

Discovery and Characterization of Alamandine

Discovery and Characterization of Alamandine

Mas and Its Related G Protein–Coupled Receptors, Mrgprs

Identification of potential tissue-specific cancer biomarkers and development of cancer versus normal genomic classifiers

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