scholarly journals MiR-23a induced the activation of CDC42/PAK1 pathway and cell cycle arrest in human granulosa cells by targeting FGD4

2020 ◽  
Author(s):  
Ji Lin ◽  
Huijuan Huang ◽  
Liheng Lin ◽  
Weiwei Li ◽  
Jianfen Huang
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Granulosa Cells ◽  
Follicular Development ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Human Granulosa Cells ◽  
Cycle Arrest ◽  
Proliferation And Apoptosis ◽  
Healthy Control

Abstract Background MiRNAs play important roles in the development of ovarian cancer, activation of primitive follicles, follicular development, oocyte maturation and ovulation. In the present study, we investigated the specific role of miR-23a in human granulosa cells. Results Downregulation of miR-23a was observed in in serum of PCOS patients compared with the healthy control, suggesting the inhibitory effect of miR-23a in PCOS. MiR-23a was positively correlated with Body Mass Index (BMI) and negatively correlated with Luteinizing hormone (LH), Testostrone (T), Glucose (Glu) and Insulin (INS) of PCOS patients. MiR-23a mimic inhibited the proliferation and promoted apoptosis of human granulosa cells. In addition, flow cytometry assay confirmed that miR-23a blocked cell cycle on G0/G1 phase. MiR-23a inhibitor showed opposite results. Furthermore, double luciferase reporter assay proved that miR-23a could bind to the 3’UTR of FGD4 directly through sites predicted on Target Scan. FGD4 level was significantly suppressed by miR-23a mimic, but was significantly enhanced by miR-23a inhibitor. We further proved that miR-23a increased the expression of activated CDC42 (GTP bround) and p-PAK-1, suggesting that miR-23a induced cell cycle arrest through CDC42/PAK1 pathway. Conclusions In conclusion, our study reveals that miR-23a participates in the regulation of proliferation and apoptosis of ovarian granulosa cells through target FGD4, and may play a role in the pathophysiology of PCOS.

scholarly journals MiR-23a induced the activation of CDC42/PAK1 pathway and cell cycle arrest in human ovarian granulosa cells by targeting FGD4

2019 ◽  
Author(s):  
Ji Lin ◽  
Huijuan Huang ◽  
Liheng Lin ◽  
Weiwei Li ◽  
Jianfen Huang
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Granulosa Cells ◽  
Follicular Development ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Ovarian Granulosa Cells ◽  
Cycle Arrest ◽  
Proliferation And Apoptosis ◽  
Healthy Control

Abstract Background: MiRNAs play important roles in the development of ovarian cancer, activation of primitive follicles, follicular development, oocyte maturation and ovulation. In the present study, we investigated the specific role of miR-23a in human ovarian granulosa cells. Results: Downregulation of miR-23a was observed in in serum of PCOS patients compared with the healthy control, suggesting the inhibitory effect of miR-23a in PCOS. MiR-23a was positively correlated with Body Mass Index (BMI) and negatively correlated with Luteinizing hormone (LH) of PCOS patients. MiR-23a mimic inhibited the proliferation and promoted apoptosis of human ovarian granulosa cells. In addition, flow cytometry assay confirmed that miR-23a blocked cell cycle on G0/G1 phase. MiR-23a inhibitor showed opposite results. Furthermore, double luciferase reporter assay proved that miR-23a could bind to the 3’UTR of FGD4 directly through sites predicted on Target Scan. FGD4 level was significantly suppressed by miR-23a mimic, but was significantly enhanced by miR-23a inhibitor. We further proved that miR-23a increased the expression of activated CDC42 (GTP bround) and p-PAK-1, suggesting that miR-23a induced cell cycle arrest through CDC42/PAK1 pathway. Conclusions: In conclusion, our study reveals that miR-23a participates in the regulation of proliferation and apoptosis of ovarian granulosa cells through target FGD4, which may have potential for clinical diagnosis and treatment of PCOS patients.

scholarly journals MiR-23a induced the activation of CDC42/PAK1 pathway and cell cycle arrest in human cov434 cells by targeting FGD4

2020 ◽  
Author(s):  
Ji Lin ◽  
Huijuan Huang ◽  
Liheng Lin ◽  
Weiwei Li ◽  
Jianfen Huang
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Follicular Development ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Cycle Arrest ◽  
Proliferation And Apoptosis ◽  
Regulation Of Proliferation ◽  
Healthy Control

Abstract Background: MiRNAs play important roles in the development of ovarian cancer, activation of primitive follicles, follicular development, oocyte maturation and ovulation. In the present study, we investigated the specific role of miR-23a in cov434 cells. Results: Downregulation of miR-23a was observed in serum of PCOS patients compared with the healthy control, suggesting the inhibitory effect of miR-23a in PCOS. MiR-23a was positively correlated with Body Mass Index (BMI) and negatively correlated with Luteinizing hormone (LH), Testostrone (T), Glucose (Glu) and Insulin (INS) of PCOS patients. MiR-23a mimic inhibited the proliferation and promoted apoptosis of human cov434 cells. In addition, flow cytometry assay confirmed that miR-23a blocked cell cycle on G0/G1 phase. MiR-23a inhibitor showed opposite results. Furthermore, double luciferase reporter assay proved that miR-23a could bind to the 3’UTR of FGD4 directly through sites predicted on Target Scan. FGD4 level was significantly suppressed by miR-23a mimic, but was significantly enhanced by miR-23a inhibitor. We further proved that miR-23a increased the expression of activated CDC42 (GTP bround) and p-PAK-1, suggesting that miR-23a induced cell cycle arrest through CDC42/PAK1 pathway. Conclusions: In conclusion, our study reveals that miR-23a participates in the regulation of proliferation and apoptosis of cov434 cells through target FGD4, and may play a role in the pathophysiology of PCOS.

Silencing of miR-1246 Induces Cell Cycle Arrest and Apoptosis in Cisplatin-Resistant Ovarian Cancer Cells by Promoting ZNF23 Transcription

2021 ◽  
pp. 1-13
Author(s):  
Lu Cai ◽  
Qian Zhang ◽  
Lili Du ◽  
Feiyun Zheng
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Cell Cycle Progression ◽  
Luciferase Reporter ◽  
Cycle Phase ◽  
Ovarian Cancer Cells ◽  
Tunel Staining ◽  
Cycle Arrest

Ovarian cancer (OC) is the most frequent cause of death among patients with gynecologic malignancies. In recent years, the development of cisplatin (DDP) resistance has become an important reason for the poor prognosis of OC patients. Therefore, it is vital to explore the mechanism of DDP resistance in OC. In this study, microRNA-1246 (miR-1246) expression in OC and DDP-resistant OC cells was determined by RT-qPCR, and chemosensitivity to DDP was assessed by the CCK-8 assay. A dual-luciferase reporter assay was performed to confirm the interaction between miR-1246 and zinc finger 23 (<i>ZNF23</i>), while changes in <i>ZNF23</i> expression were monitored by RT-qPCR, immunofluorescence, and western blot assays. Moreover, cell proliferation, cycle phase, and apoptosis were determined by EdU staining, flow cytometry, TUNEL staining, and Hoechst staining. Our data showed that miR-1246 was highly expressed in DDP-resistant OVCAR-3 and TOV-112D cells. Functionally, overexpression of miR-1246 markedly enhanced DDP resistance and cell proliferation, and suppressed cell cycle arrest and apoptosis of OC cells. Inhibition of miR-1246 expression significantly attenuated DDP resistance and cell proliferation, and increased cell cycle arrest and apoptosis in DDP-resistant OC cells. Furthermore, <i>ZNF23</i> was identified as a target gene of miR-1246, and ZNF23 protein expression was notably downregulated in DDP-resistant OC cells. Moreover, overexpression of miR-1246 significantly downregulated the <i>ZNF23</i> levels in OVCAR-3 and TOV-112D cells, and inhibition of miR-1246 upregulated the <i>ZNF23</i> levels in the DDP-resistant OVCAR-3 and TOV-112D cells. In conclusion, miR-1246 might be a novel regulator of DDP-resistant OC that functions by regulating <i>ZNF23</i> expression in DDP-resistant cells, as well as cell proliferation, cell cycle progression, and apoptosis.

scholarly journals Gypenoside L Inhibits Proliferation of Liver and Esophageal Cancer Cells by Inducing Senescence

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1054 ◽  
Author(s):  
Jingxin Ma ◽  
Xiaopeng Hu ◽  
Chenghui Liao ◽  
Haitao Xiao ◽  
Qinchang Zhu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Esophageal Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Cancer Cell Growth ◽  
Therapeutic Drugs ◽  
Cycle Arrest ◽  
Chemical Inhibitors ◽  
Esophageal Cancer Cells

Senescence is an irreversible state of cell cycle arrest that can be triggered by multiple stimuli, such as oxygen reactive species and DNA damage. Growing evidence has proven that senescence is a tumor-suppressive approach in cancer treatment. Therefore, developing novel agents that modulate senescence may be an alternative strategy against cancer. In our study, we investigated the inhibitory effect of gypenoside L (Gyp-L), a saponin isolated from Gynostemma pentaphyllum, on cancer cell growth. We found that Gyp-L increased the SA-β-galactosidase activity, promoted the production of senescence-associated secretory cytokines, and inhibited cell proliferation of human liver and esophageal cancer cells. Moreover, Gyp-L caused cell cycle arrest at S phase, and activated senescence-related cell cycle inhibitor proteins (p21 and p27) and their upstream regulators. In addition, Gyp-L activated p38 and ERK MAPK pathways and NF-κB pathway to induce senescence. Consistently, adding chemical inhibitors efficiently counteracted the Gyp-L-mediated senescence, growth inhibition, and cell cycle arrest in cancer cells. Furthermore, treatment with Gyp-L, enhanced the cytotoxicity of clinic therapeutic drugs, including 5-fluorouracil and cisplatin, on cancer cells. Overall, these results indicate that Gyp-L inhibits proliferation of cancer cells by inducing senescence and renders cancer cells more sensitive to chemotherapy.

scholarly journals Anti-CD19 inhibits the growth of human B-cell tumor lines in vitro and of Daudi cells in SCID mice by inducing cell cycle arrest

Blood ◽  
1994 ◽  
Vol 83 (5) ◽  
pp. 1329-1336 ◽  
Author(s):  
MA Ghetie ◽  
LJ Picker ◽  
JA Richardson ◽  
K Tucker ◽  
JW Uhr ◽  
...  
Keyword(s):  
Cell Cycle ◽  
B Cell ◽  
Cell Cycle Arrest ◽  
Inhibitory Effect ◽  
Scid Mice ◽  
Cell Tumor ◽  
Cycle Arrest ◽  
A Chain

Abstract In this report, we extend our previous findings that IgG or F(ab′)2 fragments of HD37 anti-CD19 antibody (Ab) in combination with the immunotoxin (IT), RFB4-anti-CD22-deglycosylated ricin A chain (dgA) (but neither reagent alone), prolonged the survival of SCID mice with disseminated human Daudi lymphoma (SCID/Daudi mice) to 1 year at which time they still remained tumor-free. We explored the mechanisms by which the HD37 Ab exerts antitumor activity in vivo by studying its activity in vitro. We found that it has antiproliferative activity (IC50 = 5.2 - 9.8 x 10(-7) mol/L) on three CD19+ Burkitt's lymphoma cell lines (Daudi, Raji, and Namalwa) but not on a weakly CD19-positive (CD19lo) pre-B cell tumor (Nalm-6). The inhibitory effect was manifested by cell cycle arrest, but not apoptosis. Results using three additional anti-CD19 Abs, suggest that the affinity of the antibody and possibly the epitope which it recognizes may effect its capacity to transmit a signal that induces cell cycle arrest. Hence, therapeutically useful Abs may exert anti-tumor activity by a variety of mechanisms, each of which should be evaluated before undertaking clinical trials in humans.

scholarly journals MiR-15b Targets Cyclin D1 to Regulate Proliferation and Apoptosis in Glioma Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Guan Sun ◽  
Lei Shi ◽  
Shushan Yan ◽  
Zhengqiang Wan ◽  
Nan Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Therapeutic Strategy ◽  
Glioma Cells ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
Proliferation And Apoptosis

Aim. To investigate the role and mechanism of miR-15b in the proliferation and apoptosis of glioma.Methods. The miR-15b mimics were transfected into human glioma cells to upregulate the miR-15b expression. Cyclin D1 was determined by both western blotting analysis and luciferase reporter assay. Methylthiazol tetrazolium (MTT) and flow cytometry were employed to detect the cell proliferation, cell cycle, and apoptosis.Results. Overexpression of miR-15b inhibits proliferation by arrested cell cycle progression and induces apoptosis, possibly by directly targeting Cyclin D1. Both luciferase assay and bioinformatics search revealed a putative target site of miR-15b binding to the 3′-UTR of Cyclin D1. Moreover, expression of miR-15b in glioma tissues was found to be inversely correlated with Cyclin D1 expression. Enforced Cyclin D1 could abrogate the miR-15b-mediated cell cycle arrest and apoptosis.Conclusions. Our findings identified that miR-15b may function as a glioma suppressor by targeting the Cyclin D1, which may provide a novel therapeutic strategy for treatment of glioma.

Repression of Mir-106b Family Members Does Not Alter Cell Cycle Progression in Hodgkin Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4722-4722
Author(s):  
Johan H Gibcus ◽  
Lu Ping Tan ◽  
Rikst Nynke Schakel ◽  
Geert Harms ◽  
Peter Moeller ◽  
...  
Keyword(s):  
Cell Cycle ◽  
B Cell ◽  
Cell Cycle Arrest ◽  
Hodgkin Lymphoma ◽  
Cell Lines ◽  
Target Genes ◽  
Family Members ◽  
Luciferase Reporter ◽  
P21 Protein ◽  
Cycle Arrest

Abstract MicroRNAs (miRNAs) are 19–25 nucleotide long RNA molecules derived from precursor genes that inhibit the expression of target genes by binding to their 3′ UTR region. Expression of miRNAs is often tissue specific and miRNA profiling has shown specific miRNA expression patterns in both B-cell development and lymphomagenesis. Hodgkin lymphoma is derived from pre-apoptotic germinal center B-cells, although a general loss of B cell phenotype is noted. Using quantitative RT-PCR and miRNA microarray, we determined the miRNA profile of HL and compared this with the profile of a panel of B-cell non-Hodgkin lymphomas (NHL). The two methods showed a very good correlation for the expression levels of the individual miRNAs. Using a large panel of cell lines, we confirmed differential expression between HL and other B-cell lymphoma derived cell lines for 27 miRNAs. The HL specific miRNAs included miR-155, miR-21 and miR-106b seed family members miR-17-5p, miR-20a, miR-93, miR-106a and miR- 106b. Next, we performed target gene validation of predicted target genes for miR-17-5p, which is highly expressed in HL. Using luciferase reporter assays with stabilized anti-sense miR17-5p oligonucleotides, we showed that GPR137B, RAB12 and RBJ are likely miR-17-5p target genes in two different HL cell lines. Previous publications indicated that miR-106b seed family members negatively regulate the cyclin-dependent kinase inhibitor 1A (p21/CIP1) resulting in cell cycle arrest at G1. Consistent with these findings, we show that the miR-106b family members are highly expressed in L428, whereas p21 is not. However, inhibition of the miR-106b seed family members in L428 does not result in elevated p21 protein expression. Furthermore, there is no cell cycle arrest, growth reduction or increase in cell death and apoptosis after inhibition of the miR-106b seed family members. Thus, we conclude that blocking of the miR-106b seed family members does not necessarily lead to indiction of p21 protein. This suggests an additional regulatory layer of p21 expression in L428 cells.

scholarly journals Ghrelin enhances cisplatin sensitivity in HO-8910 PM human ovarian cancer cells

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yun Leng ◽  
Can Zhao ◽  
Guoliang Yan ◽  
Shuangyue Xu ◽  
Yinggui Yang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Cycle Arrest ◽  
Cyclin B1 ◽  
Inhibitory Effect ◽  
S Phase ◽  
Phase Cell ◽  
Ovarian Cancer Cells ◽  
Cycle Arrest

Abstract Background Resistance to platinum-based chemotherapy is one of the crucial problems in ovarian cancer treatment. Ghrelin, a widely distributed peptide hormone, participates in a series of cancer progression. The aim of this study is to determine whether ghrelin influences the sensitivity of ovarian cancer to cisplatin, and to demonstrate the underlying mechanism. Methods The anti-tumor effects of ghrelin and cisplatin were evaluated with human ovarian cancer cells HO-8910 PM in vitro or in vivo. Cell apoptosis and cell cycle were analyzed via flow cytometry assay. The signaling pathway and the expression of cell cycle protein were analyzed with Western Blot. Results Our results showed that treatment with ghrelin specifically inhibited cell proliferation of HO-8910 PM and sensitized these cells to cisplatin via S phase cell cycle arrest, and enhanced the inhibitory effect of cisplatin on tumor growth of HO-8910 PM derived xenografts in vivo. Treatment with ghrelin inhibited the expression of p-Erk1/2 and p-p38, which was opposite the effect of cisplatin. However, under the treatment of ghrelin, cisplatin treatment exhibited a stronger effect on inhibiting P21 expression, upregulating p-CDK1 and cyclin B1 expression, and blocking cell cycle progression. Mechanistically, ghrelin promoted S phase cell cycle arrest and upregulated p-CDK1 and cyclin B1 expression induced by cisplatin via inhibition of p38. Conclusion This study revealed a specifically inhibitory effect of ghrelin on platinum-resistance via suppressing p-P38 and subsequently promoting p-CDK1 mediated cell cycle arrest in HO-8910 PM.

scholarly journals Betulin Inhibits Lung Metastasis by Inducing Cell Cycle Arrest, Autophagy, and Apoptosis of Metastatic Colorectal Cancer Cells

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 66
Author(s):  
Yo-Han Han ◽  
Jeong-Geon Mun ◽  
Hee Dong Jeon ◽  
Ji-Ye Kee ◽  
Seung-Heon Hong
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Lung Metastasis ◽  
Therapeutic Potential ◽  
Inhibitory Effect ◽  
Water Soluble ◽  
Mitogen Activated Protein Kinase ◽  
Sw620 Cell ◽  
Cycle Arrest

Background: Colorectal cancer (CRC) is one of the diseases with high prevalence and mortality worldwide. In particular, metastatic CRC shows low probability of surgery and lacks proper treatment. In this study, we conducted experiments to investigate the inhibitory effect of betulin against metastatic CRC and related mechanisms. Methods: Water-soluble tetrazolium assay was used to determine the effect of betulin on metastatic CRC cell viability. Flow cytometry and TUNEL assay were performed to confirm whether betulin can induce apoptosis, autophagy, and cell cycle arrest. A lung metastasis mouse model was employed to estimate the anti-metastatic effect of betulin. Results: betulin decreased viability of metastatic CRC cells, including CT26, HCT116, and SW620 cell lines. Through PI3K/Akt/mTOR inactivation, betulin induced AMPK-mediated G0/G1 phase arrest and autophagy of CT26 and HCT116 cells. In addition, betulin occurred caspase-dependent apoptosis via the mitogen-activated protein kinase signaling pathway in metastatic CRC cells. Moreover, orally administered betulin significantly inhibited metastasis of CT26 cells to the lung. Conclusion: Our results demonstrate the anti-metastatic effect and therapeutic potential of betulin in metastatic CRC treatment.

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