scholarly journals Ethanol Impairs NRF2/Antioxidant and Growth Signaling in the Intact Placenta In Vivo and in Human Trophoblasts

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 669 ◽  
Author(s):  
Sambantham Shanmugam ◽  
Dhyanesh Patel ◽  
John M. Wolpert ◽  
Caezaan Keshvani ◽  
Xiaobo Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cyclin D1 ◽  
Developmental Toxicity ◽  
Ethanol Vapor ◽  
Proliferation Indices ◽  
Growth Promoting ◽  
Proliferation In Vitro

NRF2 is a redox-sensitive transcription factor that depending on the duration or magnitude of the stress, either translocates to the nucleus (beneficial) or is degraded in the cytosol (harmful). However, the role of NRF2-based mechanism(s) under ethanol (E)-induced developmental toxicity in the placental context remains unknown. Here, we used a rat prenatal model of maternal alcohol stress consisting of intermittent ethanol vapor (IEV) daily from GD11 to GD20 with a 6 h ON/18 h OFF in a vapor chamber and in vitro placental model consisting of HTR-8 trophoblasts exposed to 86 mM of E for either 24 h or 48 h. The role of NRF2 was evaluated through the NRF2-transactivation reporter assay, qRT-PCR, and Western blotting for NRF2 and cell growth-promoting protein, and cell proliferation assay. In utero and in vitro E decreased the nuclear NRF2 content and diminished its transactivation ability along with dysregulation of the proliferation indices, PCNA, CYCLIN-D1, and p21. This was associated with a ~50% reduction in cell proliferation in vitro in trophoblasts. Interestingly, this was found to be partially rescued by ectopic Nrf2 overexpression. These results indicate that ethanol-induced dysregulation of NRF2 coordinately regulates PCNA/CYCLIN-D1/p21 involving growth network, at least partially to set a stage for placental perturbations.

scholarly journals HNRNPA2B1 promotes multiple myeloma progression by increasing AKT3 expression via m6A-dependent stabilization of ILF3 mRNA

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Fengjie Jiang ◽  
Xiaozhu Tang ◽  
Chao Tang ◽  
Zhen Hua ◽  
Mengying Ke ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Proliferation ◽  
Cellular Proliferation ◽  
Aberrant Expression ◽  
The Stability ◽  
Induced Apoptosis ◽  
Proliferation In Vitro

AbstractN6-methyladenosine (m6A) modification is the most prevalent modification in eukaryotic RNAs while accumulating studies suggest that m6A aberrant expression plays an important role in cancer. HNRNPA2B1 is a m6A reader which binds to nascent RNA and thus affects a perplexing array of RNA metabolism exquisitely. Despite unveiled facets that HNRNPA2B1 is deregulated in several tumors and facilitates tumor growth, a clear role of HNRNPA2B1 in multiple myeloma (MM) remains elusive. Herein, we analyzed the function and the regulatory mechanism of HNRNPA2B1 in MM. We found that HNRNPA2B1 was elevated in MM patients and negatively correlated with favorable prognosis. The depletion of HNRNPA2B1 in MM cells inhibited cell proliferation and induced apoptosis. On the contrary, the overexpression of HNRNPA2B1 promoted cell proliferation in vitro and in vivo. Mechanistic studies revealed that HNRNPA2B1 recognized the m6A sites of ILF3 and enhanced the stability of ILF3 mRNA transcripts, while AKT3 downregulation by siRNA abrogated the cellular proliferation induced by HNRNPA2B1 overexpression. Additionally, the expression of HNRNPA2B1, ILF3 and AKT3 was positively associated with each other in MM tissues tested by immunohistochemistry. In summary, our study highlights that HNRNPA2B1 potentially acts as a therapeutic target of MM through regulating AKT3 expression mediated by ILF3-dependent pattern.

scholarly journals MiR-155-5p suppresses SOX1 to promote proliferation of cholangiocarcinoma via RAF/MEK/ERK pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Da Wang ◽  
Fei Xiong ◽  
Guanhua Wu ◽  
Wenzheng Liu ◽  
Bing Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Close Relation ◽  
Luciferase Reporter ◽  
Expression Levels ◽  
Erk Phosphorylation ◽  
Overexpressing Cell ◽  
Proliferation In Vitro

Abstract Background Accumulating evidence has demonstrated the close relation of SOX1 with tumorigenesis and tumor progression. Upregulation of SOX1 was recently shown to suppress growth of human cancers. However, the expression and role of SOX1 in cholangiocarcinoma (CCA) is not well characterized. Methods Expression levels of SOX1 in CCA tissues and normal bile duct tissues were examined using public GEO database. Western blot and immunohistochemistry were used to confirm the expression levels. Cell proliferation assay (CCK-8) and colony formation assay were performed to assess proliferation of CCA cells. A mouse model of subcutaneous transplantable tumors was used to evaluated proliferation of CCA in vivo. The putative regulating factor of SOX1 were determined using Targetscan and dual-luciferase reporter assay. Results SOX1 was downregulated in CCA tissues. Overexpression of SOX1 significantly inhibited cell proliferation in vitro and suppressed tumor growth in vivo. miR-155-5p directly targeted the 3′-untranslated region (3′UTR) of SOX1 and inhibited expression of SOX1, resulting in the activation of RAF, MEK and ERK phosphorylation, and thus CCA proliferation. However, restoration of SOX1 expression in miR-155-5p overexpressing cell lines decreased the phosphorylation level of RAF, MEK and ERK, as well as the proliferation of CCA cells. Conclusion MiR-155-5p decreased the expression of SOX1 by binding to its 3′UTR, which activated the RAF/MEK/ERK signaling pathway and promoted CCA progression.

scholarly journals MiR-155-5p Suppress SOX1 to Promote the Proliferation of Cholangiocarcinoma via RAF/MEK/ERK Pathway

2021 ◽  
Author(s):  
Da Wang ◽  
Fei Xiong ◽  
Guanhua Wu ◽  
Wenzheng Liu ◽  
Bing Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Luciferase Reporter ◽  
Phosphorylation Level ◽  
Erk Phosphorylation ◽  
Overexpressing Cell ◽  
Proliferation In Vitro ◽  
Geo Database

Abstract BackgroundAccumulating evidences indicate that SOX1 is closely related to tumorigenesis and development, upregulation of SOX1 is recently reported to suppress growth of human cancers. However, the expression and role of SOX1 in cholangiocarcinoma (CCA) remain unknown.MethodsThe expression levels of SOX1 in CCA tissues and normal bile duct tissues were examined by public GEO database, and western blot and immunohistochemistry were used to confirm the expression again. Cell proliferation assay (CCK-8) and colony formation assay were performed to determine proliferation of CCA cells. A model of transplatable subcutaneously tumors in mouse was used to evaluated proliferation of CCA in vivo. The putative regulating factor of SOX1 were disclosed by Targetscan and a dual-luciferase reporter assay.ResultsSOX1 was downregulated in CCA tissues. Overexpression of SOX1 significantly inhibited cell proliferation in vitro and tumor growth in vivo. Furthermore, miR-155-5p directly targets 3’UTR of SOX1 and inhibits expression of SOX1, resulting in the activation of RAF, MEK and ERK phosphorylation and thus CCA proliferation. However, when SOX1 expression was restored in miR-155-5p overexpressing cell lines, the phosphorylation level of RAF, MEK and ERK were decreased, as well as the proliferation of CCA cells.ConclusionMiR-155-5p could bind to the 3’UTR of SOX1 to decrease the expression of SOX1, and further activated the RAF/MEK/ERK signaling pathway to promote CCA progression.

scholarly journals Cullin-1 Regulates MG63 Cell Proliferation and Metastasis and is a Novel Prognostic Marker of Osteosarcoma

2017 ◽  
Vol 32 (2) ◽  
pp. 202-209 ◽  
Author(s):  
Qinghua Cheng ◽  
Guoyong Yin
Keyword(s):  
Cell Proliferation ◽  
Mg63 Cell ◽  
Osteosarcoma Cell ◽  
Mmp9 Expression ◽  
Proliferation And Metastasis ◽  
Reliable Marker ◽  
Proliferation In Vitro

Background There is no reliable marker available for early detection, diagnostic confirmation or disease prognosis of osteosarcoma. Cullin-1 (CUL1) is a newly reported tumor-related gene, and we aimed to unravel its role in osteosarcoma. Methods We used immunohistochemistry to analyze the correlation between CUL1 expression and clinicopathological variables and patient survival. To evaluate the function of CUL1, a group of 28 osteosarcoma patients were recruited for this study. The role of regulation of CUL1 in osteosarcoma was studied in vitro and in vivo. In addition, we further investigated the signaling pathway of CUL1 in osteosarcoma progression. Results We first discovered that CUL1 expression was up-regulated in human osteosarcoma tissues and inversely correlated with osteosarcoma differentiation. In addition, CUL1 promotes osteosarcoma cell proliferation in vitro and in vivo. We also found that CUL1 promotes osteosarcoma cell invasion and metastasis in vitro and in vivo. High levels of CUL1 promote osteosarcoma progression via up-regulation of MMP9 expression. Conclusions Our results demonstrate that increased CUL1 expression is significantly correlated with poor prognosis of patients with osteosarcoma. CUL1 might be an important marker and a therapeutic target for osteosarcoma.

scholarly journals Histone Demethylase JARID1B Is Overexpressed in Osteosarcoma and Upregulates Cyclin D1 Expression via Demethylation of H3K27me3

2018 ◽  
Vol 26 (3) ◽  
pp. 373-384 ◽  
Author(s):  
Wei Wang ◽  
Ke Zheng ◽  
Yi Pei ◽  
XiaoJing Zhang
Keyword(s):  
Cell Proliferation ◽  
Cyclin D1 ◽  
Molecular Therapy ◽  
Phase Cell ◽  
Osteosarcoma Cells ◽  
Cell Numbers ◽  
M Phase ◽  
Proliferation In Vitro

JARID1B has been proven to be upregulated in many human malignancies and is correlated with tumor progression. However, its expression and clinical significance in osteosarcoma are still unclear. Thus, the aim of this study was to explore the effects of JARID1B in osteosarcoma tumorigenesis and development. In this study, we found that the expression levels of JARID1B in osteosarcoma tissues were significantly higher than those in corresponding noncancerous bone tissues. In addition, JARID1B upregulation occurred more frequently in osteosarcoma specimens from patients with a poor prognosis. After JARID1B transfection in osteosarcoma cells, cell proliferation was significantly promoted in vitro and in vivo. On the contrary, knockdown of JARID1B inhibited cell proliferation in vitro and tumor growth in vivo. JARID1B can also decrease the G0/G1 phase cell numbers and increase the S and G2/M phase cell numbers. We further demonstrated that JARID1B regulates cyclin D1 expression through H3K27me3. These findings indicate that JARID1B may act not only as a novel diagnostic and prognostic marker but also as a potential target for molecular therapy in osteosarcoma.

scholarly journals KLF7/VPS35 axis contributes to hepatocellular carcinoma progression through CCDC85C-activated β-catenin pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yarong Guo ◽  
Bao Chai ◽  
Junmei Jia ◽  
Mudan Yang ◽  
Yanjun Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Luciferase Reporter ◽  
Aberrant Expression ◽  
Proliferation And Invasion ◽  
Hcc Cells

Abstract Objective Dysregulation of KLF7 participates in the development of various cancers, but it is unclear whether there is a link between HCC and aberrant expression of KLF7. The aim of this study was to investigate the role of KLF7 in proliferation and migration of hepatocellular carcinoma (HCC) cells. Methods CCK8, colony growth, transwell, cell cycle analysis and apoptosis detection were performed to explore the effect of KLF7, VPS35 and Ccdc85c on cell function in vitro. Xenografted tumor growth was used to assess in vivo role of KLF7. Chip-qPCR and luciferase reporter assays were applied to check whether KLF7 regulated VPS35 at transcriptional manner. Co-IP assay was performed to detect the interaction between VPS35 and Ccdc85c. Immunohistochemical staining and qRT-PCR analysis were performed in human HCC sampels to study the clinical significance of KLF7, VPS35 and β-catenin. Results Firstly, KLF7 was highly expressed in human HCC samples and correlated with patients’ differentiation and metastasis status. KLF7 overexpression contributed to cell proliferation and invasion of HCC cells in vitro and in vivo. KLF7 transcriptional activation of VPS35 was necessary for HCC tumor growth and metastasis. Further, co-IP studies revealed that VPS35 could interact with Ccdc85c in HCC cells. Rescue assay confirmed that overexpression of VPS35 and knockdown of Ccdc85c abolished the VPS35-medicated promotion effect on cell proliferation and invasion. Finally, KLF7/VPS35 axis regulated Ccdc85c, which involved in activation of β-catenin signaling pathway, confirmed using β-catenin inhibitor, GK974. Functional studies suggested that downregulation of Ccdc85c partly reversed the capacity of cell proliferation and invasion in HCC cells, which was regulated by VPS35 upregulation. Lastly, there was a positive correlation among KLF7, VPS35 and active-β-catenin in human HCC patients. Conclusion We demonstrated that KLF7/VPS35 axis promoted HCC cell progression by activating Ccdc85c-medicated β-catenin pathway. Targeting this signal axis might be a potential treatment strategy for HCC.

Effects of retinoic acid steroidal analogs on human leukemic HL60 cell proliferation in vitro and on angiogenesis in vivo

2005 ◽  
Vol 16 (2) ◽  
pp. 151-158 ◽  
Author(s):  
Evaggelia S. Arsenou ◽  
Evangelia P. Papadimitriou ◽  
Eleni Kliafa ◽  
Maria Hountala ◽  
Sotiris S. Nikolaropoulos
Keyword(s):  
Cell Proliferation ◽  
Retinoic Acid ◽  
Hl60 Cell ◽  
Proliferation In Vitro

scholarly journals Antiproliferative Effect of Androgen Receptor Inhibition in Mesenchymal Stem-Like Triple-Negative Breast Cancer

2016 ◽  
Vol 38 (3) ◽  
pp. 1003-1014 ◽  
Author(s):  
Aiyu Zhu ◽  
Yan Li ◽  
Wei Song ◽  
Yumei Xu ◽  
Fang Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative

Background/Aims: Androgen receptor (AR), a steroid hormone receptor, has recently emerged as prognostic and treatment-predictive marker in breast cancer. Previous studies have shown that AR is widely expressed in up to one-third of triple-negative breast cancer (TNBC). However, the role of AR in TNBC is still not fully understood, especially in mesenchymal stem-like (MSL) TNBC cells. Methods: MSL TNBC MDA-MB-231 and Hs578T breast cancer cells were exposed to various concentration of agonist 5-α-dihydrotestosterone (DHT) or nonsteroidal antagonist bicalutamide or untreated. The effects of AR on cell viability and apoptosis were determined by MTT assay, cell counting, flow cytometry analysis and protein expression of p53, p73, p21 and Cyclin D1 were analyzed by western blotting. The bindings of AR to p73 and p21 promoter were detected by ChIP assay. MDA-MB-231 cells were transplanted into nude mice and the tumor growth curves were determined and expression of AR, p73 and p21 were detected by Immunohistochemistry (IHC) staining after treatment of DHT or bicalutamide. Results: We demonstrate that AR agonist DHT induces MSL TNBC breast cancer cells proliferation and inhibits apoptosis in vitro. Similarly, activated AR significantly increases viability of MDA-MB-231 xenografts in vivo. On the contrary, AR antagonist, bicalutamide, causes apoptosis and exerts inhibitory effects on the growth of breast cancer. Moreover, DHT-dependent activation of AR involves regulation in the cell cycle related genes, including p73, p21 and Cyclin D1. Further investigations indicate the modulation of AR on p73 and p21 mediated by direct binding of AR to their promoters, and DHT could make these binding more effectively. Conclusions: Our study demonstrates the tumorigenesis role of AR and the inhibitory effect of bicalutamide in AR-positive MSL TNBC both in vitro and in vivo, suggesting that AR inhibition could be a potential therapeutic approach for AR-positive TNBC patients.

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