scholarly journals Simulated Microgravity Inhibits the Proliferation of Chang Liver Cells by Attenuation of the Major Cell Cycle Regulators and Cytoskeletal Proteins

2021 ◽  
Vol 22 (9) ◽  
pp. 4550
Author(s):  
Chi Nguyen Quynh Ho ◽  
Minh Thi Tran ◽  
Chung Chinh Doan ◽  
Son Nghia Hoang ◽  
Diem Hong Tran ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Simulated Microgravity ◽  
Liver Cells ◽  
Cytoskeletal Proteins ◽  
Cycle Phase ◽  
Control Group ◽  
Cell Cycle Regulators ◽  
Chang Liver

Simulated microgravity (SMG) induced the changes in cell proliferation and cytoskeleton organization, which plays an important factor in various cellular processes. The inhibition in cell cycle progression has been considered to be one of the main causes of proliferation inhibition in cells under SMG, but their mechanisms are still not fully understood. This study aimed to evaluate the effects of SMG on the proliferative ability and cytoskeleton changes of Chang Liver Cells (CCL-13). CCL-13 cells were induced SMG by 3D clinostat for 72 h, while the control group were treated in normal gravity at the same time. The results showed that SMG reduced CCL-13 cell proliferation by an increase in the number of CCL-13 cells in G0/G1 phase. This cell cycle phase arrest of CCL-13 cells was due to a downregulation of cell cycle-related proteins, such as cyclin A1 and A2, cyclin D1, and cyclin-dependent kinase 6 (Cdk6). SMG-exposed CCL-13 cells also exhibited a downregulation of α-tubulin 3 and β-actin which induced the cytoskeleton reorganization. These results suggested that the inhibited proliferation of SMG-exposed CCL-13 cells could be associate with the attenuation of major cell cycle regulators and main cytoskeletal proteins.

scholarly journals Loss of MCU prevents mitochondrial fusion in G1-S phase and blocks cell cycle progression and proliferation

2019 ◽  
Vol 12 (579) ◽  
pp. eaav1439 ◽  
Author(s):  
Olha M. Koval ◽  
Emily K. Nguyen ◽  
Velarchana Santhana ◽  
Trevor P. Fidler ◽  
Sara C. Sebag ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Mitochondrial Fission ◽  
Mitochondrial Fusion ◽  
Cycle Phase ◽  
Wild Type ◽  
Mitochondrial Fragmentation ◽  
Cycle Progression ◽  
Regulatory Circuit

The role of the mitochondrial Ca2+uniporter (MCU) in physiologic cell proliferation remains to be defined. Here, we demonstrated that the MCU was required to match mitochondrial function to metabolic demands during the cell cycle. During the G1-S transition (the cycle phase with the highest mitochondrial ATP output), mitochondrial fusion, oxygen consumption, and Ca2+uptake increased in wild-type cells but not in cells lacking MCU. In proliferating wild-type control cells, the addition of the growth factors promoted the activation of the Ca2+/calmodulin-dependent kinase II (CaMKII) and the phosphorylation of the mitochondrial fission factor Drp1 at Ser616. The lack of the MCU was associated with baseline activation of CaMKII, mitochondrial fragmentation due to increased Drp1 phosphorylation, and impaired mitochondrial respiration and glycolysis. The mitochondrial fission/fusion ratio and proliferation in MCU-deficient cells recovered after MCU restoration or inhibition of mitochondrial fragmentation or of CaMKII in the cytosol. Our data highlight a key function for the MCU in mitochondrial adaptation to the metabolic demands during cell cycle progression. Cytosolic CaMKII and the MCU participate in a regulatory circuit, whereby mitochondrial Ca2+uptake affects cell proliferation through Drp1.

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 Simulated Microgravity Reduces Proliferation and Reorganizes the Cytoskeleton of Human Umbilical Cord Mesenchymal Stem Cells

2020 ◽  
pp. 897-906
Author(s):  
H CHI ◽  
H SON ◽  
D CHUNG ◽  
L HUAN ◽  
T DIEM ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Western Blot ◽  
Umbilical Cord ◽  
Simulated Microgravity ◽  
Cellular Proliferation ◽  
Cytoskeletal Proteins ◽  
Control Group ◽  
Human Umbilical Cord

The cytoskeleton plays a key role in cellular proliferation, cell-shape maintenance and internal cellular organization. Cells are highly sensitive to changes in microgravity, which can induce alterations in the distribution of the cytoskeletal and cell proliferation. This study aimed to assess the effects of simulated microgravity (SMG) on the proliferation and expression of major cell cycle-related regulators and cytoskeletal proteins in human umbilical cord mesenchymal stem cells (hucMSCs). A WST-1 assay showed that the proliferation of SMG-exposed hucMSCs was lower than a control group. Furthermore, flow cytometry analysis demonstrated that the percentage of SMG-exposed hucMSCs in the G0/G1 phase was higher than the control group. A western blot analysis revealed there was a downregulation of cyclin A1 and A2 expression in SMG-exposed hucMSCs as well. The expression of cyclin-dependent kinase 4 (cdk4) and 6 (cdk6) were also observed to be reduced in the SMG-exposed hucMSCs. The total nuclear intensity of SMG-exposed hucMSCs was also lower than the control group. However, there were no differences in the nuclear area or nuclear-shape value of hucMSCs from the SMG and control groups. A western blot and quantitative RT-PCR analysis showed that SMG-exposed hucMSCs experienced a downregulation of β-actin and α-tubulin compared to the control group. SMG generated the reorganization of microtubules and microfilaments in hucMSCs. Our study supports the idea that the downregulation of major cell cycle-related proteins and cytoskeletal proteins results in the remodeling of the cytoskeleton and the proliferation of hucMSCs.

scholarly journals The Antimicrobial Peptide Nal-P-113 Exerts a Reparative Effect by Promoting Cell Proliferation, Migration, and Cell Cycle Progression

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Nana Liu ◽  
Shuo Guan ◽  
Hongyan Wang ◽  
Chen Li ◽  
Jyawei Cheng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Antimicrobial Peptide ◽  
Cell Cycle Progression ◽  
Control Group ◽  
Blank Control Group ◽  
Cycle Progression ◽  
Immunohistochemical Assay ◽  
And Migration ◽  
Proliferation And Migration

Objective. The primary purpose of this study was to evaluate the reparative efficacy of a novel antimicrobial peptide, Nal-P-113, in shortening the healing time of oral mucosal ulcers by promoting cell proliferation and migration and accelerating the cell cycle. Methods. Cell counting kit-8 (CCK-8) and wound-healing assays were used to evaluate the proliferation and migration of human immortalized oral epithelial cells (HIOECs). The cell cycle distribution of HIOECs was analyzed by flow cytometry. Additionally, the RNA levels of EGF, FGF-2, and TGF-β1 of HIOECs were assessed by real-time PCR. Rats were divided into three groups randomly: (a) blank control group; (b) 20 μg/mL Nal-P-113; and (c) 10 ng/mL rhEGF. An oral mucosal ulcer was induced in every rat by the application of 30% acetic acid. An immunohistochemical assay was used to assess the expression of EGF, FGF-2, and TGF-β1 in the rat oral mucosa. Results. In the CCK-8 assay, the optical density values in the Nal-P-113 and rhEGF groups were found to be significantly higher than that in the blank control group. In addition, the scratch areas in the Nal-P-113 and rhEGF groups were found to be significantly smaller (P<0.05). Cell cycle analysis showed that Nal-P-113 accelerated the entry of HIOECs into the S phase and expedited their cell cycles. The RT-PCR results suggested that Nal-P-113 upregulated the RNA levels of EGF and FGF-2 but downregulated that of TGF-β1 at 24 h and 48 h. Lastly, the immunohistochemical assay verified that Nal-P-113 changed the expression of the above cytokines in rat mucosal ulcers. Conclusion. Nal-P-113 promoted the repair of oral mucosal ulcers by increasing the EGF and FGF-2 expression and decreasing that of TGF-β1 in HIOECs, accelerating their proliferation and cell cycle progression. The application of Nal-P-113 might serve as an effective therapeutic approach for recurrent aphthous stomatitis.

scholarly journals The S-phase-induced lncRNA SUNO1 promotes cell proliferation by controlling YAP1/Hippo signaling pathway

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Qinyu Hao ◽  
Xinying Zong ◽  
Qinyu Sun ◽  
Yo-Chuen Lin ◽  
You Jin Song ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Rna Polymerase Ii ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Cancer Prognosis ◽  
Cycle Phase ◽  
Hippo Signaling ◽  
Cycle Progression

Cell cycle is a cellular process that is subject to stringent control. In contrast to the wealth of knowledge of proteins controlling the cell cycle, very little is known about the molecular role of lncRNAs (long noncoding RNAs) in cell-cycle progression. By performing genome-wide transcriptome analyses in cell-cycle-synchronized cells, we observed cell-cycle phase-specific induction of >2000 lncRNAs. Further, we demonstrate that an S-phase-upregulated lncRNA, SUNO1, facilitates cell-cycle progression by promoting YAP1-mediated gene expression. SUNO1 facilitates the cell-cycle-specific transcription of WTIP, a positive regulator of YAP1, by promoting the co-activator, DDX5-mediated stabilization of RNA polymerase II on chromatin. Finally, elevated SUNO1 levels are associated with poor cancer prognosis and tumorigenicity, implying its pro-survival role. Thus, we demonstrate the role of a S-phase up-regulated lncRNA in cell-cycle progression via modulating the expression of genes controlling cell proliferation.

scholarly journals STAU2 protein level is controlled by caspases and the CHK1 pathway and regulates cell cycle progression in the non-transformed hTERT-RPE1 cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lionel Condé ◽  
Yulemi Gonzalez Quesada ◽  
Florence Bonnet-Magnaval ◽  
Rémy Beaujois ◽  
Luc DesGroseillers
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Steady State ◽  
Posttranscriptional Regulation ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Cycle Progression

AbstractBackgroundStaufen2 (STAU2) is an RNA binding protein involved in the posttranscriptional regulation of gene expression. In neurons, STAU2 is required to maintain the balance between differentiation and proliferation of neural stem cells through asymmetric cell division. However, the importance of controlling STAU2 expression for cell cycle progression is not clear in non-neuronal dividing cells. We recently showed that STAU2 transcription is inhibited in response to DNA-damage due to E2F1 displacement from theSTAU2gene promoter. We now study the regulation of STAU2 steady-state levels in unstressed cells and its consequence for cell proliferation.ResultsCRISPR/Cas9-mediated and RNAi-dependent STAU2 depletion in the non-transformed hTERT-RPE1 cells both facilitate cell proliferation suggesting that STAU2 expression influences pathway(s) linked to cell cycle controls. Such effects are not observed in the CRISPR STAU2-KO cancer HCT116 cells nor in the STAU2-RNAi-depleted HeLa cells. Interestingly, a physiological decrease in the steady-state level of STAU2 is controlled by caspases. This effect of peptidases is counterbalanced by the activity of the CHK1 pathway suggesting that STAU2 partial degradation/stabilization fines tune cell cycle progression in unstressed cells. A large-scale proteomic analysis using STAU2/biotinylase fusion protein identifies known STAU2 interactors involved in RNA translation, localization, splicing, or decay confirming the role of STAU2 in the posttranscriptional regulation of gene expression. In addition, several proteins found in the nucleolus, including proteins of the ribosome biogenesis pathway and of the DNA damage response, are found in close proximity to STAU2. Strikingly, many of these proteins are linked to the kinase CHK1 pathway, reinforcing the link between STAU2 functions and the CHK1 pathway. Indeed, inhibition of the CHK1 pathway for 4 h dissociates STAU2 from proteins involved in translation and RNA metabolism.ConclusionsThese results indicate that STAU2 is involved in pathway(s) that control(s) cell proliferation, likely via mechanisms of posttranscriptional regulation, ribonucleoprotein complex assembly, genome integrity and/or checkpoint controls. The mechanism by which STAU2 regulates cell growth likely involves caspases and the kinase CHK1 pathway.

Modulation effects of hexamethylene bisacetamide on growth and differentiation of cultured human malignant glioma cells

1996 ◽  
Vol 84 (5) ◽  
pp. 831-838 ◽  
Author(s):  
Xiao-Nan Li ◽  
Zi-Wei Du ◽  
Qiang Huang
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Malignant Glioma ◽  
Culture Media ◽  
Morphological Changes ◽  
Control Group ◽  
Cell Cycle Distribution ◽  
Content Type ◽  
Hexamethylene Bisacetamide ◽  
Human Malignant Glioma

✓ The modulation effects of hexamethylene bisacetamide (HMBA), a differentiation-inducing agent, on growth and differentiation of cells from human malignant glioma cell line SHG-44 were studied. At cytostatic doses (2.5 mM, 5 mM, 7.5 mM, and 10 mM for 15 days), HMBA exerted a marked inhibitory effect on cell proliferation. Exposure to HMBA (5 mM and 10 mM for 12 days) also resulted in an accumulation of cells in G0/G1 phase and a decrease of cells in S phase as analyzed by flow cytometry. The reversible effects of 7.5 mM HMBA and 10 mM HMBA on cell proliferation and 10 mM HMBA on disruption of cell cycle distribution were observed when HMBA was removed from culture media on Day 6 and replaced with HMBA-free media. Colony-forming efficiency (CFE) in soft agar was remarkably decreased by HMBA (2.5 mM, 5 mM, 7.5 mM, and 10 mM for 14 days), and in 7.5 mM HMBA— and 10 mM HMBA—treated cells, the CFEs were reduced to 25% and 12.5%, respectively, of that in untreated cells. Cells treated with HMBA (5 mM and 10 mM for 15 days) remained tumorigenic in athymic nude mice, but the growth rates of the xenografts were much slower than those in the control group. The effects of HMBA on cell proliferation, cell cycle distribution, CFE, and growth of xenografts were dose dependent. A more mature phenotype was confirmed by the morphological changes from spindle shape to large polygonal stellate shape and remarkably elevated expression of glial fibrillary acidic protein in cells exposed to HMBA (5 mM, 10 mM for 15 days). Our results showed that a more differentiated phenotype with marked growth arrest was induced in SHG-44 cells by HMBA.

scholarly journals LMNB2 promotes the progression of colorectal cancer by silencing p21 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Chen-Hua Dong ◽  
Tao Jiang ◽  
Hang Yin ◽  
Hu Song ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Gene Set Enrichment Analysis ◽  
Molecular Therapy ◽  
Cycle Progression ◽  
Cancer Tissues

AbstractColorectal cancer is the second common cause of death worldwide. Lamin B2 (LMNB2) is involved in chromatin remodeling and the rupture and reorganization of nuclear membrane during mitosis, which is necessary for eukaryotic cell proliferation. However, the role of LMNB2 in colorectal cancer (CRC) is poorly understood. This study explored the biological functions of LMNB2 in the progression of colorectal cancer and explored the possible molecular mechanisms. We found that LMNB2 was significantly upregulated in primary colorectal cancer tissues and cell lines, compared with paired non-cancerous tissues and normal colorectal epithelium. The high expression of LMNB2 in colorectal cancer tissues is significantly related to the clinicopathological characteristics of the patients and the shorter overall and disease-free cumulative survival. Functional analysis, including CCK8 cell proliferation test, EdU proliferation test, colony formation analysis, nude mouse xenograft, cell cycle, and apoptosis analysis showed that LMNB2 significantly promotes cell proliferation by promoting cell cycle progression in vivo and in vitro. In addition, gene set enrichment analysis, luciferase report analysis, and CHIP analysis showed that LMNB2 promotes cell proliferation by regulating the p21 promoter, whereas LMNB2 has no effect on cell apoptosis. In summary, these findings not only indicate that LMNB2 promotes the proliferation of colorectal cancer by regulating p21-mediated cell cycle progression, but also suggest the potential value of LMNB2 as a clinical prognostic marker and molecular therapy target.

scholarly journals Hyperbaric oxygen promotes not only glioblastoma proliferation but also chemosensitization by inhibiting HIF1α/HIF2α-Sox2

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Pan Wang ◽  
Sheng Gong ◽  
Jinyu Pan ◽  
Junwei Wang ◽  
Dewei Zou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Hyperbaric Oxygen ◽  
Cell Cycle Progression ◽  
Malignant Progression ◽  
Cycle Progression ◽  
Chemotherapy Sensitivity ◽  
Hypoxic Conditions ◽  
Cycle Arrest

AbstractThere exists a consensus that combining hyperbaric oxygen (HBO) and chemotherapy promotes chemotherapy sensitivity in GBM cells. However, few studies have explored the mechanism involved. HIF1α and HIF2α are the two main molecules that contribute to GBM malignant progression by inhibiting apoptosis or maintaining stemness under hypoxic conditions. Moreover, Sox2, a marker of stemness, also contributes to GBM malignant progression through stemness maintenance or cell cycle arrest. Briefly, HIF1α, HIF2α and Sox2 are highly expressed under hypoxia and contribute to GBM growth and chemoresistance. However, after exposure to HBO for GBM, whether the expression of the above factors is decreased, resulting in chemosensitization, remains unknown. Therefore, we performed a series of studies and determined that the expression of HIF1α, HIF2α and Sox2 was decreased after HBO and that HBO promoted GBM cell proliferation through cell cycle progression, albeit with a decrease in stemness, thus contributing to chemosensitization via the inhibition of HIF1α/HIF2α-Sox2.

scholarly journals The Olive Leaves Extract Has Anti-Tumor Effects against Neuroblastoma through Inhibition of Cell Proliferation and Induction of Apoptosis

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2178
Author(s):  
Fabio Morandi ◽  
Veronica Bensa ◽  
Enzo Calarco ◽  
Fabio Pastorino ◽  
Patrizia Perri ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Viability ◽  
Cell Cycle Progression ◽  
Treatment Strategies ◽  
Annexin V ◽  
Dependent Manner ◽  
Induction Of Apoptosis ◽  
Dose Dependent

Neuroblastoma (NB) is the most common extra-cranial solid tumor of pediatric age. The prognosis for high-risk NB patients remains poor, and new treatment strategies are desirable. The olive leaf extract (OLE) is constituted by phenolic compounds, whose health beneficial effects were reported. Here, the anti-tumor effects of OLE were investigated in vitro on a panel of NB cell lines in terms of (i) reduction of cell viability; (ii) inhibition of cell proliferation through cell cycle arrest; (iii) induction of apoptosis; and (iv) inhibition of cell migration. Furthermore, cytotoxicity experiments, by combining OLE with the chemotherapeutic topotecan, were also performed. OLE reduced the cell viability of NB cells in a time- and dose-dependent manner in 2D and 3D models. NB cells exposed to OLE underwent inhibition of cell proliferation, which was characterized by an arrest of the cell cycle progression in G0/G1 phase and by the accumulation of cells in the sub-G0 phase, which is peculiar of apoptotic death. This was confirmed by a dose-dependent increase of Annexin V+ cells (peculiar of apoptosis) and upregulation of caspases 3 and 7 protein levels. Moreover, OLE inhibited the migration of NB cells. Finally, the anti-tumor efficacy of the chemotherapeutic topotecan, in terms of cell viability reduction, was greatly enhanced by its combination with OLE. In conclusion, OLE has anti-tumor activity against NB by inhibiting cell proliferation and migration and by inducing apoptosis.

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