MTUS1 , a gene encoding angiotensin-II type 2 (AT2) receptor-interacting proteins, in health and disease, with special emphasis on its role in carcinogenesis

Bozgeyik, İbrahim; Yumrutaş, Önder; Bozgeyik, Esra

doi:10.1016/j.gene.2017.05.019

Cited by 25 publications

(19 citation statements)

References 59 publications

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“…Nevertheless, GBC remains aggressive, needing new biomarkers. MTUS1 is a tumor-suppressor gene as was shown in several studies (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Thus, the expression of MTUS1 protein and mRNA in tumor tissues was significantly lower than that in normal tissues of several human tumor types, including breast cancer, gastric carcinoma, head and neck squamous cell carcinoma, salivary adenoid cystic carcinoma, and urinary bladder cancer (8,11,13,16,17).…”

Section: Kaplan-meier Analysis For Cancer-specific (A) and Disease-mentioning

confidence: 87%

Loss of MTUS1 Expression Is Associated With Poor Prognosis in Patients With Gallbladder Carcinoma

Sim¹,

Kim²,

Kim³

et al. 2019

In Vivo

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Background/Aim: Microtubule-associated scaffold protein 1 (MTUS1) acts as tumor suppressor in several cancer types. This study assessed the relationship between clinicopathological characteristics and expression of microRNA candidates based on MTUS1 expression in gallbladder cancer (GBC). Materials and Methods: MTUS1 expression was evaluated by immunohistochemical staining of tissue microarrays from 109 cases of GBC. The association of MTUS1 expression with clinicopathological factors was explored. Two microRNA candidates (miR-19a-3p, and miR-19b-3p), which were identified by a literature review and computational analysis, were assessed in GBC tissue samples by quantitative real-time polymerase chain reaction. Results: Low MTUS1 expression in GBC was associated with high histological grade, perineural invasion, lymphovascular invasion, high T-stage, advanced TNM stage, poorer disease-free survival, and poorer cancer-specific survival. No statistical association between MTUS1 expression and expression of microRNA candidates was observed. Conclusion: MTUS1 may act as tumor suppressor and might be a potential biomarker for predicting prognosis in GBC. Although gallbladder cancer (GBC) is rare, it is the most common malignant tumor of the biliary tract (1-4). No specific symptoms or reliable diagnostic markers are established for GBC. In addition, GBC is diagnosed late; moreover, systemic chemotherapy and radiation therapy do not produce significant improvement in survival or quality of life for patients with GBC (1-3). Thus, patients with GBC do not have a favorable clinical outcome (1-3). Therefore, it is essential to evaluate new biomarkers for predicting the prognosis of patients with GBC. Microtubule-associated scaffold protein 1 (MTUS1), also known as angiotensin II receptor-interacting protein (ATIP), is located on chromosome 8p22 and contains 17 exons (5, 6). MTUS1 acts as a tumor-suppressor gene, exhibiting low expression in a variety of malignancies, including breast, colorectal, head and neck, ovary, stomach, salivary gland, and urinary bladder cancer (7-18). MicroRNAs (miRNAs) are short, noncoding RNAs that regulate gene expression by binding target mRNA at the post-transcriptional level. As miRNA pairing targets mRNAs in an imperfect manner, a single miRNA can target multiple genes; and one gene may be affected by multiple miRNAs (1, 19, 20). Recently, Ge et al. demonstrated that miR-19a and miR-19b co-regulate MTUS1 in lung cancer (14). Kara et al. reported decreased MTUS1 expression and elevated miR-183-5p expression in advanced stages of breast cancer (10). Additionally, several miRNAs including miR-135b-5p, miR-373-3p, miR-183-5p, miR-142-5p, miR-200c-3p, and miR-19a-3p, may play important roles in colorectal carcinoma through MTUS1 (21). The role of MTUS1 as a tumor suppressor has been reported, however, the expression of MTUS1 and its clinicopathological significance in GBC has not yet been evaluated. Thus, this study aimed to assess the clinicopathological parameters in association with MTUS1 expr...

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Section: Kaplan-meier Analysis For Cancer-specific (A) and Disease-mentioning

confidence: 87%

Loss of MTUS1 Expression Is Associated With Poor Prognosis in Patients With Gallbladder Carcinoma

Sim¹,

Kim²,

Kim³

et al. 2019

In Vivo

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“…MTUS1 is a tumor suppressor gene that is reported to be frequently down-regulated in a variety of human cancers including pancreas, colon, bladder, ovarian, breast cancers, gastric, lung cancers [ 12 ]. It is also implicated in several types of pathologies such as cardiac hypertrophy, atherosclerosis, and SLE-like lymphoproliferative diseases [ 12 ]. However, there is no literature that investigates the function of MTUS1 in the uterus.…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondrial tumor suppressor 1 ( MTUS1 ) gene is known as a candidate tumor suppressor gene encoding a family of angiotensin II receptor-interacting proteins (ATIP) [ 12 ]. It is located at chromosome 8p21.3–22 in humans [ 13 ], and its allelic losses have been documented to be associated with many cancer types such as colon, pancreas, breast, lung, bladder, and prostate cancers.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial tumor suppressor 1 is a target of AT-rich interactive domain 1A and progesterone receptor in the murine uterus

Chang

Teasley

Yoo

et al. 2018

Asian-Australas J Anim Sci

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ObjectiveProgesterone receptor (PGR) and AT-rich interactive domain 1A (ARID1A) have important roles in the establishment and maintenance of pregnancy in the uterus. In present studies, we examined the expression of mitochondrial tumor suppressor 1 (MTUS1) in the murine uterus during early pregnancy as well as in response to ovarian steroid hormone treatment.MethodsWe performed quantitative reverse transcription polymerase chain reaction and immunohistochemistry analysis to investigate the regulation of MTUS1 by ARID1A and determined expression patterns of MTUS1 in the uterus during early pregnancy.ResultsThe expression of MTUS1 was detected on day 0.5 of gestation (GD 0.5) and then gradually increased until GD 3.5 in the luminal and glandular epithelium. However, the expression of MTUS1 was significantly reduced in the uterine epithelial cells of Pgrcre/+Arid1af/f and Pgr knockout (PRKO) mice at GD 3.5. Furthermore, MTUS1 expression was remarkably induced after P4 treatment in the luminal and glandular epithelium of the wild-type mice. However, the induction of MTUS1 expression was not detected in uteri of Pgrcre/+Arid1af/f or PRKO mice treated with P4.ConclusionThese results suggest that MTUS1 is a novel target gene by ARID1A and PGR in the uterine epithelial cells.

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“…Intracellular protein trafficking is a highly regulated process controlled by interactions with specific accessory proteins (also named molecular chaperones) (Ciruela et al 2010 ; Filipeanu 2015 ; Rodemer and Haucke 2008 ). Indeed, AT 1 R-associated protein (ATRAP) was shown to interact with AT 1 R (Lopez-Ilasaca et al 2003 ) and microtubule-associated tumor suppressor gene (MTUS1)/ AT 2 R interacting protein (ATIP) with AT 2 R (Bozgeyik et al 2017 ). Interestingly, at least one MTUS1/ATIP isoform, ATIP3a was reported to be co-localized with microtubules, which form the cell cytoskeleton (Bozgeyik et al 2017 ).…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, AT 1 R-associated protein (ATRAP) was shown to interact with AT 1 R (Lopez-Ilasaca et al 2003 ) and microtubule-associated tumor suppressor gene (MTUS1)/ AT 2 R interacting protein (ATIP) with AT 2 R (Bozgeyik et al 2017 ). Interestingly, at least one MTUS1/ATIP isoform, ATIP3a was reported to be co-localized with microtubules, which form the cell cytoskeleton (Bozgeyik et al 2017 ). No such proteins are yet known for ACE and ACE2, but because both enzymes are internalized from plasma membrane to endosomes (Deshotels et al 2014 ; Lucero et al 2010 ), the availability of such accessory proteins can be predicted.…”

Section: Introductionmentioning

confidence: 99%

The Actin Bundling Protein Fascin-1 as an ACE2-Accessory Protein

et al. 2020

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We have previously shown that angiotensin-converting enzyme 2 (ACE2), an enzyme counterbalancing the deleterious effects of angiotensin type 1 receptor activation by production of vasodilatory peptides Angiotensin (Ang)-(1-9) and Ang-(1-7), is internalized and degraded in lysosomes following chronic Ang-II treatment. However, the molecular mechanisms involved in this effect remain unknown. In an attempt to identify the accessory proteins involved in this effect, we conducted a proteomic analysis in ACE2-transfected HEK293T cells. A single protein, fascin-1, was found to differentially interact with ACE2 after Ang-II treatment for 4 h. The interactions between fascin-1 and ACE2 were confirmed by confocal microscopy and co-immunoprecipitation. Overexpression of fascin-1 attenuates the effects of Ang-II on ACE2 activity. In contrast, downregulation of fascin-1 severely decreased ACE2 enzymatic activity. Interestingly, in brain homogenates from hypertensive mice, we observed a significant reduction of fascin-1, suggesting that the levels of this protein may change in cardiovascular diseases. In conclusion, we identified fascin-1 as an ACE2-accessory protein, interacting with the enzyme in an Ang-II dependent manner and contributing to the regulation of enzyme activity.

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MTUS1 , a gene encoding angiotensin-II type 2 (AT2) receptor-interacting proteins, in health and disease, with special emphasis on its role in carcinogenesis

Cited by 25 publications

References 59 publications

Loss of MTUS1 Expression Is Associated With Poor Prognosis in Patients With Gallbladder Carcinoma

Loss of MTUS1 Expression Is Associated With Poor Prognosis in Patients With Gallbladder Carcinoma

Mitochondrial tumor suppressor 1 is a target of AT-rich interactive domain 1A and progesterone receptor in the murine uterus

The Actin Bundling Protein Fascin-1 as an ACE2-Accessory Protein

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