LncRNA gas5 regulates granulosa cell apoptosis and viability following radiation by x-ray via sponging miR-205- 5p and Wnt/β-catenin signaling pathway in granulosa cell tumor of ovary

Purpose: To investigate the role of lncRNA gas5 in ovarian granulosa cells exposed to x-ray in granulosa cell tumor of ovary (GCTO). Methods: KGN cell line was exposed to X-ray to mimic the radiotherapy for GCSO patients in vitro, cell viability was checked by CCK8 assays. RNA expression of apoptosis-related genes was determined by quantitative reverse transcriptase-polymerase reaction (qRT-PCR) while Western Blot for biomarkers in wnt/β-catenin signaling. Differential expressions of lncRNA gas5 were examined after cells were exposed to a ray for 0,24,48hs. We over expressed gas5 and assessed resultant cell viability, apoptosis and signaling. The sponging between gas5 and miR-205-5p was verified by luciferase assay. CCK8, qRT-PCR and Western blot were applied to investigate the correlation between miR-205-5p, cell viability, and apoptosis after miR-205-5p augmentation. Similarly, interaction between gas5 and miR-205-5p was assessed after co-transfection of miR-205-5p mimics and oe-gas5. Finally, wnt inhibitor was used to study the role of signaling pathway in KGN cells. Results: Exposure of KGN to x-ray reduced cell viability and increased apoptosis. Gas5showed reduced expression in the cells, while miR-205-5p expression increased. Gas5 upregulation protected the cells against apoptosis and contributed to cell viability and activation of wnt//β-catenin signaling. lncRNA gas5 targeted miR-205-5p and miR-205-5p mimics counteracted the functions of up-regulated lncRNA gas5, regulating Wnt/β-catenin signaling pathway. Inactivation of Wnt/β-catenin suppressed cell viability. Conclusions: lncRNA gas5 regulates cell apoptosis and viability following cellular radiation, thus presenting a potential therapeutic target for the application radiotherapy in GCTO patients. Keywords: Ovary, Proliferation, Apoptosis, lncRNA gas5, Radiotherapy, β-catenin signaling

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LncRNA gas5 regulates granulosa cell apoptosis and viability following radiation by X-ray through sponging miR-205-5p and Wnt/β-catenin signaling pathway ingranulosa cell tumor of ovary

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i12.2 ◽

2021 ◽

Vol 19 (12) ◽

pp. 2491-2498

Author(s):

Yan Li ◽

Xing Ma ◽

Jun Li ◽

Saifei He ◽

Juhua Zhuang ◽

...

Keyword(s):

Western Blot ◽

Cell Viability ◽

Signaling Pathway ◽

Granulosa Cell ◽

Cell Apoptosis ◽

Cell Tumor ◽

Luciferase Assay ◽

X Ray ◽

Lncrna Gas5

Purpose: The study explored the role of lncRNA gas5 in ovarian granulosa cells exposed to X-ray in granulosa cell tumor of ovary(GCTO). Methods:Exposed the KGN cell line (KALANG, Beijing, China) to X-ray to mimic the radiotherapy for GCSO patients in vitro, cell viability was checked by CCK8 assays. RT-qPCR detected the RNA expression of apoptosis-related genes while Western Blot for biomarkers in wnt/β-catenin signaling. Differential expressions of lncRNA gas5 were examined after cells exposed to X ray for 0,24,48hs. We over expressed gas5 and assessed resultant cell viabilities, apoptosis and signaling. The sponging between gas5 and miR-205-5p was verified through Luciferase Assay. CCK8, RT-qPCR and Western Blot were applied for investigations into the correlation between miR-205-5p and cell viability and apoptosis after miR-205-5p augmentation. Similarly, the interactions between the gas5 and miR-205-5p were assessed after co-transfection of miR-205-5p mimics and oe-gas5. Last, wnt inhibitor was used to study the role of signaling pathway in KGN cells. Results: Exposure of KGN toX-ray reduced cell viabilities and increased apoptosis. Gas5 had reduced expression in cells while miR-205-5p increased. Gas5 upregulation could protect the cells from apoptosis and add to the cell viability and activation of wnt//β-catenin signaling. lncRNA gas5 targeted miR-205-5p and miR-205-5p mimics could counteract functions of up-regulated lncRNA gas5, regulating Wnt/β-catenin signaling pathway. Inactivation in Wnt/β-catenin could suppress cell viability. Conclusions: lncRNA gas5 regulated the cell apoptosis and viability after cellular radiation, which might be a potential therapeutic target to combine into radiotherapy for GCTO patients in clinical stage. Keywords: Ovary, proliferation, apoptosis, lncRNA gas5, x-ray

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FOXO1 mitigates the SMAD3/FOXL2C134W transcriptomic effect in a model of human adult granulosa cell tumor

Journal of Translational Medicine ◽

10.1186/s12967-021-02754-0 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Christian Secchi ◽

Paola Benaglio ◽

Francesca Mulas ◽

Martina Belli ◽

Dwayne Stupack ◽

...

Keyword(s):

Granulosa Cell ◽

Chromatin Remodeling ◽

Granulosa Cell Tumor ◽

Cell Tumor ◽

Rna Seq ◽

Pathogenic Role ◽

Rare Type ◽

Cellular Models ◽

Genome Wide

Abstract Background Adult granulosa cell tumor (aGCT) is a rare type of stromal cell malignant cancer of the ovary characterized by elevated estrogen levels. aGCTs ubiquitously harbor a somatic mutation in FOXL2 gene, Cys134Trp (c.402C < G); however, the general molecular effect of this mutation and its putative pathogenic role in aGCT tumorigenesis is not completely understood. We previously studied the role of FOXL2C134W, its partner SMAD3 and its antagonist FOXO1 in cellular models of aGCT. Methods In this work, seeking more comprehensive profiling of FOXL2C134W transcriptomic effects, we performed an RNA-seq analysis comparing the effect of FOXL2WT/SMAD3 and FOXL2C134W/SMAD3 overexpression in an established human GC line (HGrC1), which is not luteinized, and bears normal alleles of FOXL2. Results Our data shows that FOXL2C134W/SMAD3 overexpression alters the expression of 717 genes. These genes include known and novel FOXL2 targets (TGFB2, SMARCA4, HSPG2, MKI67, NFKBIA) and are enriched for neoplastic pathways (Proteoglycans in Cancer, Chromatin remodeling, Apoptosis, Tissue Morphogenesis, Tyrosine Kinase Receptors). We additionally expressed the FOXL2 antagonistic Forkhead protein, FOXO1. Surprisingly, overexpression of FOXO1 mitigated 40% of the altered genome-wide effects specifically related to FOXL2C134W, suggesting it can be a new target for aGCT treatment. Conclusions Our transcriptomic data provide novel insights into potential genes (FOXO1 regulated) that could be used as biomarkers of efficacy in aGCT patients.

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Reassessing the role of chemotherapy in the treatment of granulosa cell tumor of the ovary

Gynecologic Oncology ◽

10.1016/0090-8258(91)90155-x ◽

1991 ◽

Vol 40 (2) ◽

pp. 178

Author(s):

S. Leipzig ◽

L. Rodriguez-Rodriguez

Keyword(s):

Granulosa Cell ◽

Granulosa Cell Tumor ◽

Cell Tumor

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FOXL2, GATA4, and SMAD3 Co-Operatively Modulate Gene Expression, Cell Viability and Apoptosis in Ovarian Granulosa Cell Tumor Cells

PLoS ONE ◽

10.1371/journal.pone.0085545 ◽

2014 ◽

Vol 9 (1) ◽

pp. e85545 ◽

Cited By ~ 40

Author(s):

Mikko Anttonen ◽

Marjut Pihlajoki ◽

Noora Andersson ◽

Adrien Georges ◽

David L'Hôte ◽

...

Keyword(s):

Gene Expression ◽

Cell Viability ◽

Tumor Cells ◽

Granulosa Cell ◽

Granulosa Cell Tumor ◽

Cell Tumor ◽

Ovarian Granulosa Cell ◽

Ovarian Granulosa Cell Tumor

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Dexmedetomidine Inhibited Proliferation and Invasion of Cervical Cancer Cells by Inhibiting the Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription Signaling Pathway

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2702 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1293-1304

Author(s):

FenLan Xu ◽

Liying Xu ◽

Xiaoyan Xu ◽

Zhenhua Huang ◽

Liang Su

Keyword(s):

Cervical Cancer ◽

Cell Migration ◽

Western Blot ◽

Cell Viability ◽

Signaling Pathway ◽

Migration And Invasion ◽

Cell Migration And Invasion ◽

Stat Signaling ◽

Related Proteins

The role of anesthetics in the treatment of cancer has been reported, but the role of Dexmedetomidine (Dex) in the treatment of cervical cancer (CC) has not been reported.In this study, cell viability and proliferation were determined by MTT and cloning formation assay. The expression of proliferation-related proteins ki67 and PCNA was detected by western blot. Wound healing and transwell detected cell migration and invasion, and western blot detected the expression of migration and invasion related proteins MMP4 and MMP9, and epithelial-mesenchymal transformation (ETM)-related proteins N-cadherin, Snail, Vimentin and E-cadherin. Western blot also detected the expression of pathway related proteins p-JAK2, p-STAT1, p-STAT3, JAK2, STAT1 and STAT3. It showed that Dex inhibited the cell viability and proliferation of Hela and siHa and the expression of ki67 and PCNA were also inhibited. Dex inhibited the cell migration and invasion, and inhibited the expression of MMP4 and MMP9. In addition, Dex inhibited the expression of N-cadherin, Snail and Vimentin, and promoted the expression of E-cadherin. Dex inhibited the expression of p-JAK2, p-STAT1 and p-STAT3. After the addition of JAK/STAT signaling pathway agonist IL-6, the inhibition of Dex on proliferation, migration and invasion of CC cells was reversed. And the addition of JAK/STAT signaling pathway inhibitor AG490 could counteract the excitatory effect of IL-6 on the pathway, at which time the cell proliferation, invasion and migration were significantly increased. In conclusion, our study demonstrated that Dex inhibited proliferation, migration, and invasion of cells in CC by blocking the JAK/STAT signaling pathway.

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USP18 Mediates Interferon Resistance of Dengue Virus Infection

Frontiers in Microbiology ◽

10.3389/fmicb.2021.682380 ◽

2021 ◽

Vol 12 ◽

Author(s):

Haiyan Ye ◽

Xiaoqiong Duan ◽

Min Yao ◽

Lan Kang ◽

Yujia Li ◽

...

Keyword(s):

Dengue Virus ◽

Western Blot ◽

Signaling Pathway ◽

Hela Cells ◽

Denv Infection ◽

Luciferase Assay ◽

Type I ◽

Qrt Pcr ◽

Stat Signaling

Previous studies demonstrated that dengue virus (DENV) infection developed resistance to type-I interferons (IFNα/β). The underlying mechanism remains unclear. USP18 is a negative regulator of IFNα/β signaling, and its expression level is significantly increased following DENV infection in cell lines and patients’ blood. Our previous study revealed that increased USP18 expression contributed to the IFN-α resistance of Hepatitis C Virus (HCV). However, the role of USP18 in DENV replication and resistance to IFN-α is elusive. In this current study, we aimed to explore the role of USP18 in DENV-2 replication and resistance to IFN-α. The level of USP18 was up-regulated by plasmid transfection and down-regulated by siRNA transfection in Hela cells. USP18, IFN-α, IFN-β expression, and DENV-2 replication were monitored by qRT-PCR and Western blot. The activation of the Jak/STAT signaling pathway was assessed at three levels: p-STAT1/p-STAT2 (Western blot), interferon-stimulated response element (ISRE) activity (Dual-luciferase assay), and interferon-stimulated genes (ISGs) expression (qRT-PCR). Our data showed that DENV-2 infection increased USP18 expression in Hela cells. USP18 overexpression promoted DENV-2 replication, while USP18 silence inhibited DENV-2 replication. Silence of USP18 potentiated the anti-DENV-2 activity of IFN-α through activation of the IFN-α-mediated Jak/STAT signaling pathway as shown by increased expression of p-STAT1/p-STAT2, enhanced ISRE activity, and elevated expression of some ISGs. Our data indicated that USP18 induced by DENV-2 infection is a critical host factor utilized by DENV-2 to confer antagonism on IFN-α.

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Adult ovarian granulosa cell tumor: Role of systemic chemotherapy and surgical treatment.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e18083 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e18083-e18083

Author(s):

Anna Beliaeva ◽

Elena Bakhidze

Keyword(s):

Surgical Treatment ◽

Adjuvant Chemotherapy ◽

Drug Treatment ◽

Granulosa Cell ◽

Critical Role ◽

Granulosa Cell Tumor ◽

Cell Tumor ◽

Low Grade ◽

Significant Difference

e18083 Background: Granulosa cell tumor (GCT) are rare sex cord-stromal tumours. Their frequency is approximately 3% - 5% of all malignant ovarian tumors, and the incidence is from 0.6 to 2.1 cases per 100 000 women per year. According to the histological features, GCT are divided into two types: adult and juvenile. In the 2014 WHO histological classification, GCT were divided into borderline, which included the GCT of the juvenile type, and the malignant GCT of the adult type (AGCT). Despite the definition of AGCT not as borderline, but as low-grade malignant tumors, there are no specific recommendations for the surgical and drug treatment in such patients. Main method of treatment is surgical. Role of systemic treatment due to rarity of AGCT and late recurrence still has not determined. Methods: Data of 93 patients in our institution who were diagnosed with AGCT I-IV stage of the disease between 1980 and 2017 were evaluated. The data were obtained from the files of the patients, electronic database of the gynecologic oncology clinic, operation notes, and pathology records. Results: Stage of the disease, the spread of the tumor beyond the capsule and the number of mitoses of more than 10 significantly influenced the OS rates (p < 0.05). The average time before the onset of the first relapse in IA, IB stage was 134.5 months, in IC stage - 67.4 months, in II-IV stage - 34.3 months. Stage of the disease is an independent prognostic factor for the occurrence of a relapse of the disease. In stage I disease there was no influence of the volume of surgical treatment and adjuvant chemotherapy on DFS and the duration of disease-free period (p > 0.05). The duration of the non-progressive period was some, but not significantly more when performing optimal cytoreduction for the recurrence of the disease, and did not depend on the implementation regimen and adjuvant chemotherapy. Conclusions: There were not found significant difference in the overall and relapse-free survival of patients with ovarian AGCT, depending on the options of surgical and drug treatment they underwent. Studies showed that hormones play a critical role in the pathogenesis and treatment of GCT, especially in some ineffective cases for radiotherapy and chemotherapy. Additional multicenter randomized trials are needed to clarify the effectiveness of the various options for surgical and drug treatment of adult GCT patients.

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Role of Anti-Müllerian Hormone in Diagnosing Granulosa Cell Tumor: A Case Report

Clinical Ovarian and Other Gynecologic Cancer ◽

10.1016/j.cogc.2012.12.001 ◽

2012 ◽

Vol 5 (2) ◽

pp. 94-96

Author(s):

Aarti Umranikar ◽

Mili Saran ◽

Nick Brook ◽

Neeta Singh ◽

Darren Fowler ◽

...

Keyword(s):

Case Report ◽

Granulosa Cell ◽

Granulosa Cell Tumor ◽

Cell Tumor

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MiR-146b protects against pediatric pneumonia progression through MyD88/NF-κB signaling pathway

10.21203/rs.2.11998/v1 ◽

2019 ◽

Author(s):

Lei Zhang ◽

Lili Dong ◽

Yu Tang ◽

Min Li ◽

Mingming Zhang

Keyword(s):

Western Blot ◽

Cell Viability ◽

Signaling Pathway ◽

Cell Model ◽

Human Fibroblasts ◽

Underlying Mechanism ◽

Inflammatory Factors ◽

Pediatric Pneumonia ◽

Apoptosis Proteins

Abstract Background Pneumonia is a common respiratory disease worldwide that can be prevented and treated. However, it is considered to be the leading cause of children death. The present study was aimed to explore the role of miR-146b and its underlying mechanism in lipopolysaccharide (LPS)-induced inflammation injury in pediatric pneumonia. Methods Human fibroblasts WI-38 cells treated with LPS were subjected to construct cell model with inflammation injury. QRT-PCR or Western blot was applied to detect miR-146b and MyD88 expression. ELISA kit was used to analyze the production of pro-inflammatory factors. Cell viability was evaluated by CCK-8 assay. The apoptosis proteins and the downstream genes of NF-κB pathway were detected by Western blot. Results We displayed that miR-146b was downregulated, whereas MyD88 was upregulated in children with pneumonia and in WI-38 cells treated with LPS. Moreover, re-expression of miR-146b suppressed the production of inflammatory factors in the serum of pneumonia patients and WI-38 cells. Also, elevating miR-146b expression increased cell viability and reduced cell apoptosis. However, MyD88 overturned the protective effect of miR-146b on inflammation injury in pediatric pneumonia. Moreover, miR-146b overexpression inhibited the activation of NF-κB signaling pathway by suppressing MyD88. Conclusions These findings revealed that miR-146b attenuated the inflammation injury in pediatric pneumonia through inhibiting MyD88/NF-κB signaling pathway.

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