scholarly journals Inhibitory roles of the mammalian GnIH ortholog RFRP3 in testicular activities in adult mice

2014 ◽  
Vol 223 (1) ◽  
pp. 79-91 ◽  
Author(s):  
Shabana Anjum ◽  
Amitabh Krishna ◽  
Kazuyoshi Tsutsui
Keyword(s):  
Cell Proliferation ◽  
Germ Cell ◽  
Inhibitory Effect ◽  
The Body ◽  
Adult Mice ◽  
Gonadotropin Inhibitory Hormone ◽  
Different Doses ◽  
Germ Cell Proliferation

The aim of this study was to evaluate the effects ofin vivoandin vitrotreatments with RFamide-related peptide 3 (RFRP3), a mammalian gonadotropin-inhibitory hormone ortholog, on testicular activities, i.e. spermatogenesis and steroidogenesis, in mice. Mice were treatedin vivowith different doses of RFRP3 (control: 0.02 μg, 0.2 μg, and 2.0 μg/day) for 8 days. Forin vitrostudy, the testes of mice were evaluated with different doses of RFRP3 (control: 1 and 10 ng/ml) with or without LH (control: 10 and 100 ng/ml) for 24 h at 37 °C. RFRP3 treatment produced significant changes in the body mass, circulating steroid level, and testicular activity in mice. RFRP3 treatment also caused dose-dependent histological changes in spermatogenesis, such as decline in germ cell proliferation and survival markers and increase in apoptotic markers in testis. Bothin vivoandin vitrostudies showed the inhibitory effect of RFRP3 on testosterone synthesis in the testis. RFRP3 inhibited the expression of the receptor for LH (LHCGR), STAR protein, cytochrome P450 side-chain cleavage (CYP11A1) and 3β-hydroxysteroid dehydrogenase in the testis, and testosterone secretion dose dependently. This study also suggested that the inhibitory effect of RFRP3 in the testis may be mediated through local production of GnRH. Thus, RFRP3 inhibits testicular steroidogenesis and spermatogenesis either indirectly through GnRH or by directly influencing germ cell proliferation, survival, and apoptosis.

Bradykinin stimulates prepubertal rat germ cell proliferation in vitro

1998 ◽  
Vol 40 (3) ◽  
pp. 173-178 ◽  
Author(s):  
Nina Atanassova ◽  
Ludmila Kancheva ◽  
Boris Somlev
Keyword(s):  
Cell Proliferation ◽  
Germ Cell ◽  
Proliferation In Vitro ◽  
Germ Cell Proliferation

scholarly journals A Potential Role of Progestin-Induced Laminin-5/α6-Integrin Signaling in the Formation of Side Branches in the Mammary Gland

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4990-5001 ◽  
Author(s):  
Gabriele Meyer ◽  
Jeffrey Leipprandt ◽  
Jianwei Xie ◽  
Mark D. Aupperlee ◽  
Sandra Z. Haslam
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Nuclear Factor Κb ◽  
Inhibitory Effect ◽  
Collagen Gels ◽  
Paracrine Factor ◽  
Laminin 5 ◽  
Adult Mice

Abstract Mammary organoids from adult mice produce tubules, analogous to mammary ducts in vivo, in response to hepatocyte growth factor (HGF) when cultured in collagen gels. The combination of HGF plus progestin (R5020) causes reduced tubule number and length. We hypothesized that the inhibitory effect on tubulogenesis was due to progestin-mediated alteration of HGF/c-Met signaling. Using molecular inhibitors and short hairpin RNA, it was determined that HGF activation of Ras-related C3 botulinum toxin substrate (Rac1) was required for the formation of cytoplasmic extensions, the first step of tubulogenesis, and that Rac1 activity was Src kinase (Src) and focal adhesion kinase (FAK) dependent. The highly novel finding was that R5020 reduced tubulogenesis by up-regulating and increasing extracellular laminin and α6-integrin ligation to reduce activation of the Src, focal adhesion kinase, and Rac1 pathway. Receptor activator of nuclear factor-κB ligand, another progesterone-induced paracrine factor, did not replicate this effect of R5020. The inhibitory effect of R5020 on tubulogenesis was likely mediated through progesterone receptor (PR) isoform A (PRA), because PRA is the predominant PR isoform expressed in the organoids, and the progestin-induced effect was prevented by the PR antagonist RU486. These results provide a plausible mechanism that explains progestin/PRA-mediated blunting of HGF-induced tubulogenesis in vitro and is proposed to be relevant to progesterone/PRA-induced side-branching in vivo during pregnancy.

scholarly journals Human Bone Marrow-Derived Mesenchymal Stem Cell-Secreted Exosomes Overexpressing Microrna-124-3p Inhibit DLBCL Progression By Downregulating  NFATc1

2020 ◽  
Author(s):  
Xiaolei Ding ◽  
Lingzhi Xu ◽  
Xiuhua Sun ◽  
Xiaoxuan Zhao ◽  
Bing Gao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
B Cell Lymphoma ◽  
Inhibitory Effect ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Proliferation And Apoptosis ◽  
Microrna 124

Abstract Background: Exosomes play important roles in intercellular communication by delivering microRNAs (miRNAs) that mediate tumor initiation and development, including those in diffuse large B cell lymphoma (DLBCL). To date, however, limited studies on the inhibitory effect of exosomes derived from human bone marrow-derived mesenchymal stem cells (hBMSCs) on DLBCL progression have been reported. Therefore, this study aimed to investigate the role of hBMSC-secreted exosomes carrying microRNA-124-3p in the development of DLBCL.Methods: Microarray-based expression analysis was adopted to identify differentially expressed genes and regulatory miRNAs, which revealed the candidate NFATc1. Next, the binding affinity between miR-124-3p and NFATc1 was using luciferase activity assays. The mechanism underlying NFATc1 regulation was investigated using lentiviral transfections. Subsequently, DLBCL cells were cocultured with exosomes derived from hBMSCs transfected with a miR-124-3p mimic or control. Proliferation and apoptosis were measured in vitro. Finally, the effects of hBMSC-derived miR-124-3p on tumor growth were investigated in vivo.Results: MiR-124-3p was downregulated while NFATc1 was upregulated in DLBCL cells. MiR-124-3p specifically targeted and negatively regulated the expression of NFATc1 in DLBCL cells, upregulated miR-124-3p-inhibited DLBCL cell proliferation and promoted apoptosis. In addition, we found that hBMSC-derived exosomes carrying miR-124-3p repressed DLBCL cell proliferation both in vitro and in vivo.Conclusion: hBMSC-derived exosomal miR-124-3p represses the development of DLBCL through the downregulation of NFATc1.

scholarly journals NLRR1 Is a Potential Therapeutic Target in Neuroblastoma and MYCN-Driven Malignant Cancers

2021 ◽  
Vol 11 ◽  
Author(s):  
Atsushi Takatori ◽  
Shamim Hossain ◽  
Atsushi Ogura ◽  
Jesmin Akter ◽  
Yohko Nakamura ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Inhibitory Effect ◽  
Tumor Cell Proliferation ◽  
Growth Inhibitory Effect ◽  
Extracellular Domains ◽  
Growth Inhibitory ◽  
Fniii Domain

Receptor tyrosine kinases (RTKs) receive different modulation before transmitting proliferative signals. We previously identified neuronal leucine-rich repeat 1 (NLRR1) as a positive regulator of EGF and IGF-1 signals in high-risk neuroblastoma cells. Here, we show that NLRR1 is up-regulated in various adult cancers and acts as a key regulator of tumor cell proliferation. In the extracellular domains of NLRR1, fibronectin type III (FNIII) domain is responsible for its function to promote cell proliferation. We generated monoclonal antibodies against the extracellular domains of NLRR1 (N1mAb) and screened the positive N1mAbs for growth inhibitory effect. The treatment of N1mAbs reduces tumor cell proliferation in vitro and in vivo, and sensitizes the cells to EGFR inhibitor, suggesting that NLRR1 is a novel regulatory molecule of RTK function. Importantly, epitope mapping analysis has revealed that N1mAbs with growth inhibitory effect recognize immunoglobulin-like and FNIII domains of NLRR1, which also indicates the importance of FNIII domain in the function of NLRR1. Thus, the present study provides a new insight into the development of a cancer therapy by targeting NLRR1 as a modulator of proliferative signals on cellular membrane of tumor cells.

LncRNA DUXAP8 promotes the progression of laryngeal cancer through targeting miR-384/ POU2F1 axis

2020 ◽  
Author(s):  
Zhanfeng Yan ◽  
Xiaohui Wen ◽  
Jinsheng Dai ◽  
Jinfeng Liu ◽  
Pengpeng Hao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Laryngeal Cancer ◽  
Tumor Model ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
High Level

Abstract Background Laryngeal cancer is the highest incidence of head and neck cancers in the world. Increasing evidences have demonstrated that long non-coding RNAs (lncRNAs) play crucial roles in the progression of laryngeal cancer. Despite of the essential role of lncRNA DUXAP8 in many human cancers, its function and specific mechanisms in laryngeal cancer are poorly understood. Methods Differentially expression analysis of lncRNAs in GSE59652 dataset was performed by using limma package of R language. The expression of DUXAP8, miR-384 and candidate mRNAs was evaluated by qRT-PCR. Luciferase reporter assay and RIP assay were performed to determine the direct correlation between DUXAP8, miR-384 and POU2F1. Cell proliferation of laryngeal cancer cell lines TU212 and TU177 cells was evaluated by using CCK-8 assay, colony formation assay and EdU staining assay. Xenograft tumor model in vivo and rescue experiments were performed to explore the function and mechanisms of DUXAP8 in laryngeal cancer. Results The expression of DUXAP8 in tumor tissues was higher than that in adjacent normal tissues. High level of DUXAP8 was closely correlated to the worse prognosis of laryngeal cancer patients. Knockdown of DUXAP8 inhibited the proliferation of TU212 and TU177 cells in vitro, as well as tumor growth in vivo. Furthermore, overexpression of POU2F1 significantly attenuated the inhibitory effect of sh-DUXAP8 on cell proliferation of TU212 and TU177 cells. In addition, sh-DUXAP8 significantly decreased the expression of DUXAP8 and POU2F1, while increased miR-384 expression in tumor tissues compared with sh-NC group. Conclusion DUXAP8 acted as a sponge of tumor suppressor miR-384 and then upregulated POU2F1 expression, thereby promoted the development of laryngeal cancer. Our findings suggest that DUXAP8 may serve as a potential therapeutic target for laryngeal cancer.

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