FSH receptor binding inhibitor impacts K-Ras and c-Myc of ovarian cancer and signal pathway

Wei, Shaozhong; Shen, Xıaoyun; Lai, Liangxue; Liang, Huaping; Deng, Yingying; Gong, Zhuandı; Che, Tuanjie

doi:10.18632/oncotarget.25139

Cited by 10 publications

(10 citation statements)

References 32 publications

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“…Interestingly, PSPO2 is known to play an important role in ovarian follicular growth (Bouilly et al 2017) and is involved in some developmentally related signaling pathways (Dong et al 2017;Ilmer et al 2015). In addition, FSH genetic variations have been associated with genital lesions and infertility in males (André et al 2018;Tamburino et al 2017) as well as with ovary and various female gonad developmental processes (Wei et al 2018). Therefore, the significantly higher expression levels of these two genes in IG pituitary tissues are insufficient to explain the molecular mechanism of intersexual goats, but they may be involved in the maintenance of the physiological phenotype and biological regulation of intersexual goats.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide analysis of Chongqing native intersexual goats using next-generation sequencing

et al. 2019

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Sex reversal has been studied extensively in vertebrate species, particularly in domestic goats, because polled intersex syndrome (PIS) has seriously affected their production efficiency. In the present study, we used histopathologically diagnosed cases of PIS to identify correlated genomic regions and variants using representative selection signatures and performed GWAS using Restriction-Site Associated Resequencing DNA. We identified 171 single-nucleotide polymorphisms (SNPs) that may have contributed to this phenotype, and 53 SNPs were determined to be located in coding regions using a general linear model. The transcriptome data sets of differentially expressed genes (DEGs) in the pituitary tissues of intersexual and nonintersexual goats were examined using high-throughput technology. A total of 10,063 DEGs and 337 long noncoding RNAs were identified. The DEGs were clustered into 56 GO categories and determined to be significantly enriched in 53 signaling pathways by KEGG analysis. In addition, according to qPCR results, PSPO2 and FSH were significantly more highly expressed in sexually mature pituitary tissues of intersexual goats compared to healthy controls (nonintersexual). These results demonstrate that certain novel potential genomic regions may be responsible for intersexual goats, and the transcriptome data indicate that the regulation of various physiological systems is involved in intersexual goat development. Therefore, these results provide helpful data for understanding the molecular mechanisms of intersex syndrome in goats.

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Section: Discussionmentioning

confidence: 99%

Genome-wide analysis of Chongqing native intersexual goats using next-generation sequencing

et al. 2019

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“…Among multiple malignancies, such as breast cancer, prostate cancer, lung cancer, and ovarian cancer, excessive activation of c-Myc is thought to be involved in tumorigenesis and tumor development 36. The overexpression of c-Myc protein is likely to promote the process of malignancy and tumor progression 37. High c-Myc expression is associated with high recurrence, poor overall survival, and cisplatin resistance in these patients with high-grade serous ovarian cancer 38.…”

Section: Discussionmentioning

confidence: 99%

<p>Sphingosine kinase 2 inhibitor ABC294640 displays anti-epithelial ovarian cancer activities in vitro and in vivo</p>

Song¹,

Dai²,

Long³

et al. 2019

OTT

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Background: ABC294640 is a non-lipid competitive inhibitor of SphK2. It exhibited anti-proliferative activities in many human malignancies, including ovarian cancer. However, its potential mechanism of action remains poorly understood. Methods: In this paper, epithelial ovarian cancer (EOC) cell lines SKOV3 and HO8910 were treated with ABC294640. In order to explore the effect of ABC294640 on the behavior of ovarian cancer cells in vitro, we used cell counting kit-8 (CCK-8) assays, colony formation assays, flow cytometry, quantitative real-time PCR (qRT-PCR), Western blot analysis and immunohistochemistry to detect the effect of ABC294640 on cell proliferation, cell cycle distribution, cell apoptosis, the expression of related factors at mRNA levels, and the expression of related factors at protein level. An intra-abdominal xenograft tumor model of EOC was set up to assess the tumor growth in nude mice. Results: The results obtained indicate that EOC cell proliferation was noticeably inhibited in a concentration-dependent manner by ABC294640. ABC294640 caused cell cycle arrest in S phase and increased cell apoptosis rate in EOC cells. Also, the proteins, including phosphorylated retinoblastoma protein ( P - Rb), cyclin D1, cyclin B1, and Bcl-2 were significantly inhibited, while cleaved-caspase 3 was activated. ABC294640 inhibited the expression of c-Myc in EOC. The in vivo assay showed an inhibitory effect of ABC294640 on tumor growth. Conclusions: ABC294640 could downregulate the expression of c-Myc in EOC both in vitro and in vivo. ABC294640 inhibited tumor growth in EOC via cell cycle arrest and inducing cell apoptosis both in vitro and in vivo, partially by decreasing the expression of cell cycle–associated proteins (such as P -Rb, cyclin B1, and cyclin D1) and promoting caspase 3 activation via downregulation expression of c-Myc. It suggested that ABC294640 had the potential to serve as an agent in EOC treatment.

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“…Their expression levels are correlated to carcinogenesis of ovarian and gynecologic cancers (6). There is little information regarding the influence of FRBI on ARID1A, PTEN, and FSHR associated with ovarian cancers (21,22) and no quantitative research has been reported about the correlation between ovarian carcinogenesis and levels of ARID1A and PTEN in humans and animals (1,23).…”

Section: Discussionmentioning

confidence: 99%

“…Our results were consistent with an earlier report (9). Therefore, FRBI, as a novel biomarker, could be utilized for early diagnosis and therapy of ovarian cancers (22). The actual effects of FRBI on anticancer activity and progression of ovarian cancers will need to be thoroughly investigated in the future (1).…”

Section: Discussionmentioning

confidence: 99%

FSH receptor binding inhibitor up-regulates ARID1A and PTEN genes associated with ovarian cancers in mice

Gong

Shen

Yang

et al. 2019

Braz J Med Biol Res

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Experiments were conducted to determine if the follicle-stimulating hormone (FSH) receptor binding inhibitor (FRBI) impacts the expression levels of AT-rich interactive domain-containing protein 1A (ARID1A) and phosphatase and tensin homolog (PTEN) in ovaries and blood, as well as expressions of follicle-stimulating hormone cognate receptor (FSHR) gene and proteins. Mice in FRBI-10, FRBI-20, FRBI-30, and FRBI-40 groups were intramuscularly injected with 10, 20, 30, and 40 mg FRBI/kg, respectively, for five consecutive days. Western blotting and qRT-PCR were utilized to determine expression levels of ARID1A and PTEN proteins and mRNAs. Serum ARID1A and PTEN concentrations of the FRBI-40 group were higher than the control group (CG) and FSH group (P<0.05). FSHR mRNA levels of FRBI-20, FRBI-30, and FRBI-40 groups were lower than that of CG and FSH groups on day 15 (P<0.05 or P<0.01). Expression levels of FSHR proteins of FRBI-30 and FRBI-40 groups were lower than those of CG and FSH groups (P<0.05). Levels of ARID1A and PTEN proteins of the FRBI-30 group were greater than CG on days 20 and 30 (P<0.05). FRBI doses had significant positive correlations to levels of ARID1A and PTEN proteins. Additionally, ARID1A and PTEN had negative correlations to FSHR mRNAs and proteins. A high dose of FRBI could promote the expression levels of ARID1A and PTEN proteins in ovarian tissues. FRBI increased serum concentrations of ARID1A and PTEN. However, FRBI depressed expression levels of FSHR mRNAs and proteins in mouse ovaries.

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FSH receptor binding inhibitor impacts K-Ras and c-Myc of ovarian cancer and signal pathway

Cited by 10 publications

References 32 publications

Genome-wide analysis of Chongqing native intersexual goats using next-generation sequencing

Genome-wide analysis of Chongqing native intersexual goats using next-generation sequencing

<p>Sphingosine kinase 2 inhibitor ABC294640 displays anti-epithelial ovarian cancer activities in vitro and in vivo</p>

FSH receptor binding inhibitor up-regulates ARID1A and PTEN genes associated with ovarian cancers in mice

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