FSH receptor binding inhibitor depresses carcinogenesis of ovarian cancer via decreasing levels of K-Ras, c-Myc and FSHR

Yang, Juan; Gong, Zhuandı; Shen, Xıaoyun; Bai, Shengju; Bai, Xiaoqiang; Wei, Shaozhong

doi:10.1080/10495398.2019.1656083

Cited by 6 publications

(3 citation statements)

References 29 publications

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“…By adding the binding inhibitor of FSH receptor, the results show that FSHR is critical for FSH action in carcinogenesis (Gong et al, 2019; Yang et al, 2021), and FSHR may have potential therapeutic and diagnostic implication (Wei et al, 2018; Zhuandi et al, 2018). In the present study, the results showed that the overexpression of miR‐21 increased mRNA and protein levels of FSHR (Figure 12b,d), and the same trend was observed upon the inhibition of miR‐125b and let‐7b (Figure 12a,c).…”

Section: Discussionmentioning

confidence: 99%

miR‐21, miR‐125b, and let‐7b contribute to the involution of atretic follicles and corpus lutea in Tibetan sheep ovaries

Zhang

Huo

Wei

et al. 2022

Animal Science Journal

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Follicular granulosa cells (FGCs) are crucial for ovarian follicle functions, and miRNAs are differentially expressed at various stages of follicular developments. In this study, we confirmed that miR-21, miR-125b, and let-7b were located in FGCs/luteal cells by in situ hybridization experiments. Moreover, miR-21 and miR-125b expressions were upregulated in late corpus lutea (CL) and atretic follicles (AF); let-7b expression was increased in early AF. After transfected with inhibitor or mimic of miRNAs in FGCs, we found that FGCs apoptosis was decreased in the miR-21-mi group but increased in the miR-125b-mi group using flow cytometry. mRNA and protein expression levels were determined for apoptosis-related factors (e.g., Bcl-2 and Bax), the potential target genes of miRNAs (e.g., SMAD7, SP1, and STAT3), hormone receptors (e.g., FSHR and LHR), and genes related to hormone secretion (e.g., CYP19, CYP11, and 3βHSD). The protein levels of SMAD7 were decreased in the miR-21-mi group but opposite to SP1 and FSHR. In the let-7b-mi group, Bcl-2, SMAD7, and FSHR were suppressed but not Bax, CYP11, and 3βHSD. However, hormone secretion was not changed in the supernatant of transfected FGCs. This study provides information about ovarian miRNAs to improve the fertility in Tibetan sheep.

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Section: Discussionmentioning

confidence: 99%

miR‐21, miR‐125b, and let‐7b contribute to the involution of atretic follicles and corpus lutea in Tibetan sheep ovaries

Zhang

Huo

Wei

et al. 2022

Animal Science Journal

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“…CCs transcribe both MYC and THAP11 (Miles et al, 2012;Mao et al, 2014;Moura et al, 2018). The inhibition of FSHR diminished MYC mRNA and protein levels in sheep COCs and ovarian cancer cells (Wei et al, 2018;Yang et al, 2019). The differentiation of bovine granulosa cells by lactate (which mimics a preovulatory cellular phenotype) led to MYC down-regulation (Baufeld et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

MYC integrates FSH signalling networks in cumulus cells during bovine oocyte maturation

Cantanhêde

Moura

Silva

et al. 2022

AVet

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Follicle-stimulating hormone (FSH) contributes to the acquisition of oocyte competence by modulating signalling pathways in cumulus cells (CCs), albeit much less is known about transcription factors (TFs) that orchestrate the downstream transcriptional changes. This work allowed to prospect TFs involved in FSH-mediated signalling during oocyte in vitro maturation (IVM). Bovine cumulus-oocyte complexes underwent IVM with FSH (FSH+) or without FSH (control/CTL) for 22 h, and CCs were subjected to gene expression profiling. Five software identified reference genes for RT-qPCR (ATP1A1, UBB, and YWHAZ). The transcript levels of FSH-responsive genes HAS2 and PTGS2 (COX2) validated the experimental design. Among candidate TFs, MYC was down-regulated (0.35-fold; P < 0.0001), and THAP11 (RONIN) was up-regulated (1.47-fold; P = 0.016) under FSH+ conditions. In silico analyses predicted binding motifs at MYC and THAP11 genes for previously known FSH-responsive TFs. Signalling pathways (EGFR, ERK, GSK3, PKA, and P38) may execute post-translational regulation due to potential phosphorylation sites in MYC and THAP11 proteins. Prediction of protein–protein interaction networks showed MYC as a core component of FSH signalling, albeit THAP11 acts independently. Hence, MYC integrates FSH signalling networks and may assist in exploring genome-wide transcriptional changes associated with the acquisition of oocyte competence.

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“…The FSH stimulus transduces the intracellular signaling through the FSHR-mediated pathway, which leads to an increase in intracellular second messenger molecules (cAMP) and the activation of PKA [ 26 ]. In a recent investigation of the FSH receptor-binding inhibitor, K-RAS was shown to play an essential role in regulating FSH-induced cAMP production and PKA expression in ovarian granulosa cells [ 31 , 32 ]. Furthermore, PKA mediates the actions of FSH on granulosa cell membranes by signaling through multiple targets to activate the PI3K/AKT pathway, which leads to increased proliferation, inhibition of apoptosis, enhanced translation, and activation of target genes with products involved in the maturation process of pre-ovulatory granulosa cells [ 33 ].…”

Section: Potential Function Of Ras In the Ovarymentioning

confidence: 99%

The Role of the Guanosine Nucleotide-Binding Protein in the Corpus Luteum

Billhaq

Lee

2021

Animals

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The corpus luteum is a temporary endocrine gland in the ovary. In the ovarian cycle, repeated patterns of specific cellular proliferation, differentiation, and transformation occur that accompany the formation and regression of the corpus luteum. Molecular mechanism events in the ovarian microenvironment, such as angiogenesis and apoptosis, are complex. Recently, we focused on the role of RAS protein in the ovarian corpus luteum. RAS protein plays a vital role in the modulation of cell survival, proliferation, and differentiation by molecular pathway signaling. Additionally, reproductive hormones regulate RAS activity in the cellular physiological function of ovarian follicles during pre-ovulatory maturation and ovulation. Thus, we have reviewed the role of RAS protein related to the biological events of the corpus luteum in the ovary.

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FSH receptor binding inhibitor depresses carcinogenesis of ovarian cancer via decreasing levels of K-Ras, c-Myc and FSHR

Cited by 6 publications

References 29 publications

miR‐21, miR‐125b, and let‐7b contribute to the involution of atretic follicles and corpus lutea in Tibetan sheep ovaries

miR‐21, miR‐125b, and let‐7b contribute to the involution of atretic follicles and corpus lutea in Tibetan sheep ovaries

MYC integrates FSH signalling networks in cumulus cells during bovine oocyte maturation

The Role of the Guanosine Nucleotide-Binding Protein in the Corpus Luteum

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