scholarly journals Lnc-GULP1-2:1 Affects Granulosa Cell Proliferation by Regulating COL3A1 Expression and Localization​

2020 ◽  
Author(s):  
Guidong Yao ◽  
Yue Kong ◽  
Guang Yang ◽  
Deqi Kong ◽  
Yijiang Xu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Follicular Development ◽  
Protein Coding ◽  
New Strategy ◽  
Multiple Cell ◽  
And Migration ◽  
Regulation Of Cell Cycle

Abstract Backgrounds: Long non-coding RNA is a kind of RNA molecule with a transcript length of more than 200 nt and lacking protein coding ability. Recent studies have found that it is widely involved in many pathological and physiological processes. In our previous study, we found that lnc-GULP1-2:1 was significantly down-regulated in the ovarian cortical tissue of patients with primary ovarian insufficiency and predicted that lnc-GULP1-2:1 has a regulatory effect on COL3A1. Results: In this study, we found that lnc-GULP1-2:1 was mainly localized in the cytoplasm of luteinized granulosa cells and was lower expressed in patients with diminished ovarian reserve but highly expressed in patients with polycystic ovary syndrome. Overexpression of lnc-GULP1-2:1 in KGN cells significantly inhibited cell proliferation, which may be related to the regulation of cell cycle related genes CCND2 and p16. To further investigate the regulation of lnc-GULP1-2:1 on COL3A1, RNA analysis revealed a positive correlation between the expression of lnc-GULP1-2:1 and COL3A1 in multiple cell lines, and this was consistent in luteinized granulosa cells from patients with different ovarian functions. We also found that overexpression of lnc-GULP1-2:1 in KGN cells promoted the expression and migration of COL3A1 into the nucleus. Silencing COL3A1 gene in KGN cells also significantly inhibited cell proliferation, which may be related to the regulation of CCND2 gene expression. Conclusions: This study demonstrates that lnc-GULP1-2:1 may participate in the regulation of granulosa cell proliferation by regulating the expression and localization of COL3A1 protein, which will provide a new idea for understanding the regulatory mechanism of follicular development and a new strategy for the diagnosis and treatment of diseases related to follicular development disorders in the future.

scholarly journals Lnc-GULP1-2:1 affects granulosa cell proliferation by regulating COL3A1 expression and localization​

2020 ◽  
Author(s):  
Guidong Yao ◽  
Yue Kong ◽  
Guang Yang ◽  
Deqi Kong ◽  
Yijiang Xu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
Protein Coding ◽  
Ovarian Follicle Development ◽  
New Strategy ◽  
And Migration ◽  
Regulation Of Cell Cycle

Abstract Backgrounds: Long non-coding RNA is a kind of RNA molecule with a transcript length of more than 200 nt and lacking protein coding ability. Recent studies have found that it is widely involved in many pathological and physiological processes. In our previous study, we found that lnc-GULP1-2:1 was significantly down-regulated in the ovarian cortical tissue of patients with primary ovarian insufficiency and predicted that lnc-GULP1-2:1 has a regulatory effect on COL3A1. Results: In this study, we found that lnc-GULP1-2:1 was mainly localized in the cytoplasm of luteinized granulosa cells and was lower expressed in patients with diminished ovarian reserve but highly expressed in patients with polycystic ovary syndrome. Overexpression of lnc-GULP1-2:1 in KGN cells significantly inhibited cell proliferation, which may be related to the regulation of cell cycle related genes CCND2 and p16. To further investigate the regulation of lnc-GULP1-2:1 on COL3A1, RNA analysis revealed a positive correlation between the expression of lnc-GULP1-2:1 and COL3A1 in multiple cell lines, and this was consistent in luteinized granulosa cells from patients with different ovarian functions. We also found that overexpression of lnc-GULP1-2:1 in KGN cells promoted the expression and migration of COL3A1 into the nucleus, and silencing COL3A1 gene in KGN cells also significantly inhibited cell proliferation. Conclusions: Lnc-GULP1-2:1 affects the proliferation of granulosa cells by regulating the expression and localization of COL3A1 protein, and may participate in the regulation of ovarian follicle development. This study will provide a new idea for understanding the regulatory mechanism of follicular development and a new strategy for the diagnosis and treatment of diseases related to ovarian follicular development disorders in the future.

scholarly journals Lnc-GULP1-2:1 affects granulosa cell proliferation by regulating COL3A1 expression and localization​

2021 ◽  
Author(s):  
Guidong Yao ◽  
Yue Kong ◽  
Guang Yang ◽  
Deqi Kong ◽  
Yijiang Xu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cells ◽  
Molecular Mechanisms ◽  
Polycystic Ovary ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
Protein Coding ◽  
Ovarian Follicle Development ◽  
Multiple Cell ◽  
Ovarian Follicular Development

Abstract Backgrounds: Long non-coding RNA is a novel group of non-protein coding transcripts over 200nt in length. Recent studies have found that they are widely involved in many pathological and physiological processes. In our previous study, we found that lnc-GULP1-2:1 was significantly down-regulated in the ovarian cortical tissue of patients with primary ovarian insufficiency and predicted that lnc-GULP1-2:1 has a regulatory effect on COL3A1. Results: In this study, we found that lnc-GULP1-2:1 was mainly localized in the cytoplasm of luteinized granulosa cells. The expression of lnc-GULP1-2:1 was lower in patients with diminished ovarian reserve but substantially elevated in patients with polycystic ovary syndrome. Overexpression of lnc-GULP1-2:1 in KGN cells significantly inhibited cell proliferation, likely through cell cycle related genes CCND2 and p16. Moreover, lnc-GULP1-2:1 expression was positively correlated with the level of COL3A in luteinized granulosa cells from patients with different ovarian functions as well as in multiple cell lines. Overexpression of lnc-GULP1-2:1 in KGN cells promoted the expression of COL3A1 and its translocation into the nucleus. Consistently, silencing COL3A1 in KGN cells also significantly inhibited cell proliferation. Conclusions: Lnc-GULP1-2:1 affects the proliferation of granulosa cells by regulating the expression and localization of COL3A1 protein, and may participate in the regulation of ovarian follicle development. This study will provide new insight into molecular mechanisms underlying ovarian follicular development, which will help generate novel diagnostic and therapeutic strategies for diseases related to ovarian follicular development disorders.

scholarly journals Lnc-GULP1–2:1 affects granulosa cell proliferation by regulating COL3A1 expression and localization

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Guidong Yao ◽  
Yue Kong ◽  
Guang Yang ◽  
Deqi Kong ◽  
Yijiang Xu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cells ◽  
Molecular Mechanisms ◽  
Polycystic Ovary ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
Protein Coding ◽  
Ovarian Follicle Development ◽  
Multiple Cell ◽  
Ovarian Follicular Development

Abstract Backgrounds Long non-coding RNA is a novel group of non-protein coding transcripts over 200 nt in length. Recent studies have found that they are widely involved in many pathological and physiological processes. In our previous study, we found that lnc-GULP1–2:1 was significantly down-regulated in the ovarian cortical tissue of patients with primary ovarian insufficiency and predicted that lnc-GULP1–2:1 has a regulatory effect on COL3A1. Results In this study, we found that lnc-GULP1–2:1 was mainly localized in the cytoplasm of luteinized granulosa cells. The expression of lnc-GULP1–2:1 was lower in patients with diminished ovarian reserve but substantially elevated in patients with polycystic ovary syndrome. Overexpression of lnc-GULP1–2:1 in KGN cells significantly inhibited cell proliferation, likely through cell cycle related genes CCND2 and p16. Moreover, lnc-GULP1–2:1 expression was positively correlated with the level of COL3A in luteinized granulosa cells from patients with different ovarian functions as well as in multiple cell lines. Overexpression of lnc-GULP1–2:1 in KGN cells promoted the expression of COL3A1 and its translocation into the nucleus. Consistently, silencing COL3A1 in KGN cells also significantly inhibited cell proliferation. Conclusions Lnc-GULP1–2:1 affects the proliferation of granulosa cells by regulating the expression and localization of COL3A1 protein, and may participate in the regulation of ovarian follicle development. This study will provide new insight into molecular mechanisms underlying ovarian follicular development, which will help generate novel diagnostic and therapeutic strategies for diseases related to ovarian follicular development disorders.

Oocyte-secreted factros regulate granulosa cell steroidogenesis

Zygote ◽  
1996 ◽  
Vol 4 (04) ◽  
pp. 317-321 ◽  
Author(s):  
Barbara C. Vanderhyden
Keyword(s):  
Cell Proliferation ◽  
Germ Cell ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Follicular Fluid ◽  
Follicular Development ◽  
Inhibitory Factor ◽  
Preovulatory Follicles ◽  
Loss Of Contact

Investigations of strains of mice defective in germ cell development have revealed the importance of oocytes for the initial stages of folliculogenesis (Pellaset al., 1991; Huanget al., 1993). Various aspects of follicular development are dependent upon and/or influenced by the presence of oocytes, including granulosa cell proliferation (Vanderhydenet al., 1990, 1992) and cumulus expansion (Buccioneet al., 1990; Salustriet al., 1990; Vanderhydenet al., 1990; Vanderhyden, 1993). We are investigating the possibility that oocytes influence one of the primary functions of granulosa cells: steroidogenesis. In many species, granulosa cells removed from preovulatory follicles luteinisein vitro(Channinget al., 1982), presumably due to loss of contact with follicular luteinisation inhibitory factor(s). Indeed, follicular fluid can prevent granulosa cell luteinisationin vitro(Ledwitz-Rigbyet al., 1977). Follicular fluid, however, may simply be the medium for transport of factors secreted by oocytes to regulate granulosa cell activities.

Exosomal miR-143-3p Derived from PCOS Follicular Fluid Induces Granulosa Cell Apoptosis by Targeting BMPR1A and Suppression of Smad1/5/8 Signaling

2021 ◽  
Author(s):  
Yuanyuan Zhao ◽  
Shuhong Pan ◽  
Yunying Li ◽  
Xiaohua Wu
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Follicular Fluid ◽  
Cell Apoptosis ◽  
Polycystic Ovary ◽  
Follicular Development ◽  
Reproductive Age ◽  
Exosomal Mirnas ◽  
Exosomal Mirna

Abstract Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorders disease in women of reproductive age. The anovulation caused by abnormal follicular development is still the main characteristic of infertile patients with PCOS. Granulosa cells (GCs), an important component of follicular microenvironment, affect follicular development through GCs dysfunction. Increasing evidence indicates that exosomal miRNAs derived from follicular fluid (FF) of patients play critical roles during PCOS. However, which and how follicular fluid derived exosomal miRNAs play a pivotal role in controlling granulosa cells function and consequently follicular development remain largely unknown. Herein, we showed that miR-143-3p is highly expressed in follicular fluid exosomes of PCOS patients and can be delivered into granulosa cells. Furthermore, the functional experiments showed that the translocated miR-143-3p promoted granulosa cell apoptosis, which are important in follicle development. In terms of mechanism, we demonstrated that BMPR1A was identified as a direct target of miR-143-3p. Overexpression of BMPR1A reversed the effects of exosomal miR-143-3p on GCs apoptosis and proliferation by activating Smad1/5/8 signaling pathway. These results demonstrate that miR-143-3p-containing exosomes derived from PCOS follicular fluid promoted granulosa cell apoptosis by targeting BMPR1A and blockading Smad1/5/8 signaling pathway. Our findings provide a novel mechanism underlying the roles of exosomal-miRNA in follicular fluid of PCOS and facilitate the development of therapeutic strategies for PCOS.

Effect of hypothyroidism on ovarian follicular development, granulosa cell proliferation and peripheral hormone levels in the prepubertal rat

1996 ◽  
Vol 134 (5) ◽  
pp. 649-654 ◽  
Author(s):  
Grietje Dijkstra ◽  
Dirk G de Rooij ◽  
Frank H de Jong ◽  
Robert van den Hurk
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Ovarian Development ◽  
Follicular Development ◽  
Corpora Lutea ◽  
Hormone Levels ◽  
Antral Follicles ◽  
Ovarian Follicular Development ◽  
Serum Tsh

Dijkstra G, de Rooij DG, de Jong FH, van den Hurk R. Effect of hypothyroidism on ovarian follicular development, granulosa cell proliferation and peripheral hormone levels in the prepubertal rat. Eur J Endocrinol 1996;134:649–54. ISSN 0804–4643 The aim of this study was to examine the effects of prepubertal hypothyroidism on ovarian development in rats. Therefore, from birth up to day 40 postpartum, rats were given 6-propyl-2-thiouracil (PTU) via the drinking water of mothers and pups. At ages ranging from 12 to 40 days, ovarian weights were measured and serum was collected to estimate thyrotrophin (TSH), folliclestimulating hormone (FSH) and inhibin levels. Two hours before sacrifice the animals received an injection of bromodeoxyuridine (BrdU) to estimate the proliferative activity of the follicular granulosa cells. Ovaries were fixed in Carnoy's fluid and follicle counts were performed on sections stained with anti-BrdU and with haematoxylin and eosin. The PTU treatment resulted in increased serum TSH levels, indicative of hypothyroidism, and markedly lower body and ovarian weights, whereas serum FSH and inhibin levels were hardly affected. At day 40, ovaries of PTU-treated animals contained relatively more secondary and less antral follicles, smaller non-atretic antral follicles and more atretic follicles when compared with untreated rats, while corpora lutea were absent. It is concluded that this disturbed folliculogenesis is due to inadequate thyroid hormone supply, which hampers the differentiation and not the proliferation of granulosa cells because diameters of antral follicles were significantly smaller whereas the BrdU-labelling index had not changed. Robert van den Hurk, Department of Functional Morphology, Faculty of Veterinary Medicine, PO Box 80.157, 3508 TD Utrecht, The Netherlands

scholarly journals miR-3188 Regulates proliferation and apoptosis of granulosa cells by targeting KCNA5 in the polycystic ovary syndrome

2021 ◽  
Author(s):  
Shan Zhou ◽  
Liang Xia ◽  
Yuanyuan Chen ◽  
Weiying Guo ◽  
Jinxing Hu
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Polycystic Ovary Syndrome ◽  
Cell Viability ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Healthy Controls ◽  
Ovarian Dysfunction ◽  
Ovary Syndrome

Abnormal proliferation of granulosa cells is implicated in ovarian dysfunction and dysregulated folliculogenesis in the polycystic ovary syndrome (PCOS). Aberrant microRNA (miRNA) expression might contribute to disordered folliculogenesis and granulosa cell proliferation in PCOS. This study aimed to investigate the roles of miR-3188 in ovarian dysfunction, as well as the mechanism involved in granulosa cell proliferation in PCOS. Firstly, peripheral blood samples were isolated from PCOS patients and healthy controls, and qRT-PCR analysis demonstrated a dramatic increase in miR-3188 in PCOS patients when compared to the healthy controls. Secondly, miR-3188 overexpression increased cell viability of the granulosa-like tumor cell line (KGN). However, cell viability of KGN was repressed by interference with miR-3188. MiR-3188 promoted cell cycle of KGN through increasing cyclinD1 and decreasing p21 levels. Moreover, cell apoptosis was suppressed by miR-3188 in KGN, indicated by enhanced Bcl-2, and reduced Bax and cleaved caspase-3 levels, whereas knockdown of miR-3188 resulted in opposite effects. Lastly, potassium voltage-gated channel subfamily A member 5 (KCNA5) was verified as a target of miR-3188. KCNA5 expression was decreased and displayed negative correlation with miR-3188 levels in PCOS patients. Overexpression of KCNA5 attenuated the promotive effects of miR-3188 on cell viability and cell cycle in KGN. In conclusion, miR-3188, a key miRNA enhanced in PCOS, promoted granulosa cell proliferation through down-regulation of KCNA5, providing a new therapeutic target for PCOS.

scholarly journals Notch Signaling Is Involved in Ovarian Follicle Development by Regulating Granulosa Cell Proliferation

Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2437-2447 ◽  
Author(s):  
Chun-Ping Zhang ◽  
Jun-Ling Yang ◽  
Jun Zhang ◽  
Lei Li ◽  
Lin Huang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Notch Signaling ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Butyl Ester ◽  
Follicular Development ◽  
Follicle Development ◽  
Ovarian Follicle Development

Notch signaling is an evolutionarily conserved pathway, which regulates cell proliferation, differentiation, and apoptosis. It has been reported that the members of Notch signaling are expressed in mammalian ovaries, but the exact functions of this pathway in follicle development is still unclear. In this study, primary follicles were cultured in vitro and treated with Notch signaling inhibitors, L-658,458 and N-[N-(3,5-Difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT). We found that the cultured follicles completely stopped developing after L-658,458 and DAPT treatment, most of the granulosa cells were detached, and the oocytes were also degenerated with condensed cytoplasma. Further studies demonstrated that the proliferation of granulosa cells was dependent on the Notch signaling. L-658,458 and DAPT treatment inhibited proliferation of in vitro cultured primary granulosa cells and decreased the expression of c-Myc. Lentivirus mediated overexpression of Notch intracellular domain 2, and c-Myc could promote the proliferation of granulosa cells and rescue the growth inhibition induced by L-658,458 and DAPT. In conclusion, Notch signaling is involved in follicular development by regulating granulosa cell proliferation.

scholarly journals Follicle-Stimulating Hormone Inhibits Adenosine 5′-Monophosphate-Activated Protein Kinase Activation and Promotes Cell Proliferation of Primary Granulosa Cells in Culture through an Akt-Dependent Pathway

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 929-935 ◽  
Author(s):  
Pradeep P. Kayampilly ◽  
K. M. J. Menon
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Protein Kinase ◽  
Mrna Expression ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Ampk Activation ◽  
Cyclin D2 ◽  
Cell Cycle Inhibitor ◽  
Dependent Pathway

FSH, acting through multiple signaling pathways, regulates the proliferation and growth of granulosa cells, which are critical for ovulation. The present study investigated whether AMP-activated protein kinase (AMPK), which controls the energy balance of the cell, plays a role in FSH-mediated increase in granulosa cell proliferation. Cells isolated from immature rat ovaries were grown in serum-free, phenol red free DMEM-F12 and were treated with FSH (50 ng/ml) for 0, 5, and 15 min. Western blot analysis showed a significant reduction in AMPK activation as observed by a reduction of phosphorylation at thr 172 in response to FSH treatment at all time points tested. FSH also reduced AMPK phosphorylation in a dose-dependent manner with maximum inhibition at 100 ng/ml. The chemical activator of AMPK (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, 0.5 mm) increased the cell cycle inhibitor p27 kip expression significantly, whereas the AMPK inhibitor (compound C, 20 μm) and FSH reduced p27kip expression significantly compared with control. FSH treatment resulted in an increase in the phosphorylation of AMPK at ser 485/491 and a reduction in thr 172 phosphorylation. Inhibition of Akt phosphorylation using Akt inhibitor VIII reversed the inhibitory effect of FSH on thr 172 phosphorylation of AMPK, whereas ERK inhibitor U0126 had no effect. These results show that FSH, through an Akt-dependent pathway, phosphorylates AMPK at ser 481/495 and inhibits its activation by reducing thr 172 phosphorylation. AMPK activation by 5-amino-imidazole-4-carboxamide-1-β-d-ribofuranoside treatment resulted in a reduction of cell cycle regulatory protein cyclin D2 mRNA expression, whereas FSH increased the expression by 2-fold. These results suggest that FSH promotes granulosa cell proliferation by increasing cyclin D2 mRNA expression and by reducing p27 kip expression by inhibiting AMPK activation through an Akt-dependent pathway. FSH stimulates granulosa cell proliferation by reducing cell cycle inhibitor p27 kip through AMP kinase inhibition.

scholarly journals LINC01089 suppresses lung adenocarcinoma cell proliferation and migration via miR-301b-3p/STARD13 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ye Qian ◽  
Yan Zhang ◽  
Haoming Ji ◽  
Yucheng Shen ◽  
Liangfeng Zheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
High Morbidity ◽  
Lipid Transfer ◽  
Protein Coding ◽  
Cell Proliferation And Migration ◽  
Reduce Cell Proliferation ◽  
And Migration ◽  
Insight Into ◽  
Proliferation And Migration

Abstract Background Lung adenocarcinoma (LUAD) is one of the most common cancers with high morbidity and mortality worldwide. Long non-coding RNAs (lncRNAs) serve as tumor promoters or suppressors in the development of various human malignancies, including LUAD. Although long intergenic non-protein coding RNA 1089 (LINC01089) suppresses the progression of breast cancer, its mechanism in LUAD requires further exploration. Thus, we aimed to investigate the underlying function and mechanism of LINC01089 in LUAD. Methods The expression of LINC01089 in LUAD and normal cell lines was detected. Functional assays were applied to measure cell proliferation, apoptosis and migration. Besides, mechanism experiments were employed for assessing the interplay among LINC01089, miR-301b-3p and StAR related lipid transfer domain containing 13 (STARD13). Data achieved in this study was statistically analyzed with Student’s t test or one-way analysis of variance. Results LINC01089 expression was significantly down-regulated in LUAD tissues and cells and its overexpression could reduce cell proliferation and migration. Moreover, LINC01089 could regulate STARD13 expression through competitively binding to miR-301b-3p in LUAD. Additionally, rescue assays uncovered that STARD13 depletion or miR-301b-3p overexpression could countervail the restraining effect of LINC01089 knockdown on the phenotypes of LUAD cells. Conclusion LINC01089 served as a tumor-inhibitor in LUAD by targeting miR-301b-3p/STARD13 axis, providing an innovative insight into LUAD therapies. Trial registration Not applicable.

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