Downregulation of <i><scp>TBXAS</scp>1</i> in an iron‐induced malignant mesothelioma model

Minami, Daisuke; Takigawa, Nagio; Kato, Yuka; Kudo, Kenichiro; Isozaki, Hideko; Hashida, Shinsuke; Harada, Daijiro; Ochi, Nobuaki; Fujii, Masanori; Kubo, Toshio; Ohashi, Kadoaki; Satô, Akiko; Tanaka, Takehiro; Hotta, Katsuyuki; Tabata, Masahiro; Toyooka, Shinichi; Tanimoto, Mitsune; Kiura, Katsuyuki

doi:10.1111/cas.12752

Cited by 16 publications

(6 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using this established model, we detected a homozygous deletion of Cdkn2a/2b in four of five cases in sarcomatoid mesothelioma (SM) and no genomic loss of Cdkn2a/2b in epithelioid mesothelioma (EM) (0/6) 8 . The deletion of the Cdkn2a/2b genomic locus in iron saccharate‐induced MM was reproduced in one out of five cases of EM in a different group 9 . The prevalence of homozygous deletion of CDKN2A/2B , which is the most frequent genomic alteration in humans, 10,11 is reported to be 69% in EM and 100% in SM 12 .…”

Section: Introductionmentioning

confidence: 94%

Overexpression of miR‐199/214 is a distinctive feature of iron‐induced and asbestos‐induced sarcomatoid mesothelioma in rats

et al. 2020

View full text Add to dashboard Cite

Malignant mesothelioma (MM) is one of the most lethal tumors in humans. The onset of MM is linked to exposure to asbestos, which generates reactive oxygen species (ROS). ROS are believed to be derived from the frustrated phagocytosis and the iron in asbestos. To explore the pathogenesis of MM, peritoneal MM was induced in rats by the repeated intraperitoneal injection of iron saccharate and nitrilotriacetate. In the present study, we used microarray techniques to screen the microRNA (miR) expression profiles of these MM. We observed that the histological subtype impacted the hierarchical clustering of miR expression profiles and determined that miR‐199/214 is a distinctive feature of iron saccharate‐induced sarcomatoid mesothelioma (SM). Twist1, a transcriptional regulator of the epithelial‐mesenchymal transition, has been shown to activate miR‐199/214 transcription; thus, the expression level of Twist1 was examined in iron‐induced and asbestos‐induced mesotheliomas in rats. Twist1 was exclusively expressed in iron saccharate‐induced SM but not in the epithelioid subtype. The Twist1‐miR‐199/214 axis is activated in iron saccharate‐induced and asbestos‐induced SM. The expression levels of miR‐214 and Twist1 were correlated in an asbestos‐induced MM cell line, suggesting that the Twist1‐miR‐199/214 axis is preserved. MeT5A, an immortalized human mesothelial cell line, was used for the functional analysis of miR. The overexpression of miR‐199/214 promoted cellular proliferation, mobility and phosphorylation of Akt and ERK in MeT5A cells. These results indicate that miR‐199/214 may affect the aggressive biological behavior of SM.

show abstract

Section: Introductionmentioning

confidence: 94%

Overexpression of miR‐199/214 is a distinctive feature of iron‐induced and asbestos‐induced sarcomatoid mesothelioma in rats

et al. 2020

View full text Add to dashboard Cite

show abstract

“…During EA, however, with the sharp decline of VEGFA, ANGPT2 alone may induce endothelial cell apoptosis with consequent vascular regression. Moreover, endoplasmic reticulum membrane protein TBXAS1 catalyzes the conversion of prostaglandin H2 (PGH2) to thromboxane A2 (TXA2), which is a potent vasoconstrictor and inducer of platelet aggregation (Minami et al 2015). Based on their functions, we speculate firstly that greater HIF1A and VEGFA levels in healthy follicles play a role in growth of follicular vascular networks, and thus provide necessary nutrition supply to maintain healthy follicle development.…”

Section: Hif-1 Signaling and Vascular Regressionmentioning

confidence: 99%

Initiation of follicular atresia: gene networks during early atresia in pig ovaries

Zhang¹,

Liu²,

Wang³

et al. 2018

Reproduction

View full text Add to dashboard Cite

In mammals, more than 99% of ovarian follicles undergo a degenerative process known as atresia. The molecular events involved in atresia initiation remain incompletely understood. The objective of this study was to analyze differential gene expression profiles of medium antral ovarian follicles during early atresia in pig. The transcriptome evaluation was performed on cDNA microarrays using healthy and early atretic follicle samples and was validated by quantitative PCR. Annotation analysis applying current database ( 11.1) revealed 450 significantly differential expressed genes between healthy and early atretic follicles. Among them, 142 were significantly upregulated in early atretic with respect to healthy group and 308 were downregulated. Similar expression trends were observed between microarray data and quantitative RT-PCR confirmation, which indicated the reliability of the microarray analysis. Further analysis of the differential expressed genes revealed the most significantly affected biological functions during early atresia including blood vessel development, regulation of DNA-templated transcription in response to stress and negative regulation of cell adhesion. The pathway and interaction analysis suggested that atresia initiation associates with (1) a crosstalk of cell apoptosis, autophagy and ferroptosis rather than change of typical apoptosis markers, (2) dramatic shift of steroidogenic enzymes, (3) deficient glutathione metabolism and (4) vascular degeneration. The novel gene candidates and pathways identified in the current study will lead to a comprehensive view of the molecular regulation of ovarian follicular atresia and a new understanding of atresia initiation.

show abstract

“…The early genetic event at the Cdkn2a locus by exposure to either long asbestos or long carbon nanotubes was the hypermethylation of Cdkn2a , whereas deletion of Cdkn2a occurs at a late stage of the malignant transformation 40 . The homozygous deletion of Cdkn2a/2b was not observed in the epithelioid subtype (EM) (0/6), but it was observed in the sarcomatoid subtype (SM) (4/5) in our study 36 and EM (1/5) in another study 41 when iron saccharate was used for rat MM carcinogenesis. The higher rate of homozygous deletion of Cdkn2a/2b in SM is concordant with human MM 42 .…”

Section: Discussionmentioning

confidence: 82%

Frequent homozygous deletion of Cdkn2a/2b in tremolite‐induced malignant mesothelioma in rats

et al. 2020

View full text Add to dashboard Cite

The onset of malignant mesothelioma (MM) is linked to exposure to asbestos fibers.Asbestos fibers are classified as serpentine (chrysotile) or amphibole, which includes the crocidolite, amosite, anthophyllite, tremolite, and actinolite types. Although few studies have been undertaken, anthophyllite has been shown to be associated with mesothelioma, and tremolite, a contaminant in talc and chrysotile, is a risk factor for carcinogenicity. Here, after characterizing the length and width of these fibers by scanning electron microscopy, we explored the cytotoxicity induced by tremolite and anthophyllite in cells from an immortalized human mesothelial cell line (MeT5A), murine macrophages (RAW264.7), and in a rat model. Tremolite and short anthophyllite fibers were phagocytosed and localized to vacuoles, whereas the long anthophyllite fibers were caught on the pseudopod of the MeT5A and Raw 264.7 cells, according to transmission electron microscopy. The results from a 2-day time-lapse study revealed that tremolite was engulfed and damaged the MeT5A and RAW264.7 cells, but anthophyllite was not cytotoxic to these cells. Intraperitoneal injection of tremolite in rats induced diffuse serosal thickening, whereas anthophyllite formed focal fibrosis and granulomas on peritoneal serosal surfaces. Furthermore, the loss of Cdkn2a/2b, which are the most frequently lost foci in human MM, were observed in 8 cases of rat MM (homozygous deletion [5/8] and loss of heterozygosity [3/8]) by array-based comparative genomic hybridization techniques. These results indicate that tremolite initiates mesothelial injury and persistently frustrates phagocytes, causing subsequent peritoneal fibrosis and MM. The possible mechanisms of carcinogenicity based on fiber diameter/length are discussed. K E Y W O R D S animal model, anthophyllite, Cdkn2a/2b, malignant mesothelioma, tremolite 1 | INTRODUC TI ON Asbestos, which are naturally occurring fibrous minerals, are classified as carcinogens on the basis of sufficient evidence in humans; thus, many countries have banned the use of all asbestos. 1 The WHO estimates that more than 107 000 people die each year from asbestos-related lung cancer, malignant mesothelioma (MM), and asbestosis from occupational exposure. 2 Malignant | 1181 OKAZAKI et Al.

show abstract

Downregulation of TBXAS1 in an iron‐induced malignant mesothelioma model

Cited by 16 publications

References 34 publications

Overexpression of miR‐199/214 is a distinctive feature of iron‐induced and asbestos‐induced sarcomatoid mesothelioma in rats

Overexpression of miR‐199/214 is a distinctive feature of iron‐induced and asbestos‐induced sarcomatoid mesothelioma in rats

Initiation of follicular atresia: gene networks during early atresia in pig ovaries

Frequent homozygous deletion of Cdkn2a/2b in tremolite‐induced malignant mesothelioma in rats

Contact Info

Product

Resources

About