scholarly journals Knockdown of MRPL42 suppresses glioma cell proliferation by inducing cell cycle arrest and apoptosis

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Chunyan Hao ◽  
Hubin Duan ◽  
Hao Li ◽  
Huan Wang ◽  
Yueting Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ribosomal Proteins ◽  
Glioma Cells ◽  
S Phase ◽  
The Cancer Genome Atlas ◽  
Normal Tissues ◽  
Cycle Arrest ◽  
Glioma Cell Proliferation ◽  
Cancer Genome Atlas

Mammalian mitochondrial ribosomal proteins are functionally involved in protein synthesis in mitochondrion. Recently numerous studies have illuminated the role of mitochondrion in cancer development. However, the precise function of mitochondrial ribosomal protein L42 (MRPL42) remains unclear. Here in the present study, we identified MRPL42 as a novel oncogene in glioma. By analyzing the Cancer Genome Atlas (TCGA) database, we first found that MRPL42 was significantly up-regulated in glioma tissues compared with normal tissues. Functionally, we silenced MRPL42 in glioma cells and revealed that MRPL42 knockdown largely blunted the proliferation of U251 and A172 cells. Mechanistically, our results suggested that MRPL42 silencing resulted in increased distribution of cell cycle in G1 and G2/M phases, while the S-phase decreased. In addition, the apoptosis and caspase3/7 activity were both activated after MRPL42 knockdown. Taken together, MRPL42 is a novel oncogene in glioma and might help us develop promising targetted therapies for glioma patients.

scholarly journals The NUCKS1-SKP2-p21/p27 axis controls S phase entry

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Samuel Hume ◽  
Claudia P. Grou ◽  
Pauline Lascaux ◽  
Vincenzo D’Angiolella ◽  
Arnaud J. Legrand ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Transcriptional Repression ◽  
S Phase ◽  
The Cancer Genome Atlas ◽  
Cycle Arrest ◽  
Checkpoint Pathway ◽  
Cancer Genome Atlas ◽  
Dna Damage Signalling ◽  
Phase Entry

AbstractEfficient entry into S phase of the cell cycle is necessary for embryonic development and tissue homoeostasis. However, unscheduled S phase entry triggers DNA damage and promotes oncogenesis, underlining the requirement for strict control. Here, we identify the NUCKS1-SKP2-p21/p27 axis as a checkpoint pathway for the G1/S transition. In response to mitogenic stimulation, NUCKS1, a transcription factor, is recruited to chromatin to activate expression of SKP2, the F-box component of the SCFSKP2 ubiquitin ligase, leading to degradation of p21 and p27 and promoting progression into S phase. In contrast, DNA damage induces p53-dependent transcriptional repression of NUCKS1, leading to SKP2 downregulation, p21/p27 upregulation, and cell cycle arrest. We propose that the NUCKS1-SKP2-p21/p27 axis integrates mitogenic and DNA damage signalling to control S phase entry. The Cancer Genome Atlas (TCGA) data reveal that this mechanism is hijacked in many cancers, potentially allowing cancer cells to sustain uncontrolled proliferation.

MicroRNA-1225-5p acts as a tumor-suppressor in laryngeal cancer via targeting CDC14B

2019 ◽  
Vol 400 (2) ◽  
pp. 237-246 ◽  
Author(s):  
Peng Sun ◽  
Dan Zhang ◽  
Haiping Huang ◽  
Yafeng Yu ◽  
Zhendong Yang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Division ◽  
Cell Cycle Arrest ◽  
Molecular Mechanisms ◽  
Normal Tissues ◽  
Cycle Arrest ◽  
Enhanced Expression ◽  
Insight Into

Abstract This study aimed to investigate the role of miRNA-1225-5p (miR-1225) in laryngeal carcinoma (LC). We found that the expression of miR-1225 was suppressed in human LC samples, while CDC14B (cell division cycle 14B) expression was reinforced in comparison with surrounding normal tissues. We also demonstrated that enhanced expression of miR-1225 impaired the proliferation and survival of LC cells, and resulted in G1/S cell cycle arrest. In contrast, reduced expression of miR-1225 promoted cell survival. Moreover, miR-1225 resulted in G1/S cell cycle arrest and enhanced cell death. Further, miR-1225 targets CDC14B 3′-UTR and recovery of CDC14B expression counteracted the suppressive influence of miR-1225 on LC cells. Thus, these findings offer insight into the biological and molecular mechanisms behind the development of LC.

scholarly journals YTHDC1-mediated VPS25 regulates cell cycle by targeting JAK-STAT signaling in human glioma cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaolong Zhu ◽  
Hui Yang ◽  
Mengying Zhang ◽  
Xingwei Wu ◽  
Lan Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Glioma Cells ◽  
Prognostic Indicator ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Endosomal Sorting ◽  
Cancer Genome Atlas

Abstract Background Glioma is a common type of malignant brain tumor with a high mortality and relapse rate. The endosomal sorting complex required for transport (ESCRT) has been reported to be involved in tumorigenesis. However, the molecular mechanisms have not been clarified. Methods Bioinformatics was used to screen the ESCRT subunits highly expressed in glioma tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The function of the ESCRT subunits in glioma cells was examined in vitro. Transcriptome sequencing analyzed the target genes and signaling pathways affected by the ESCRT subunit. Finally, the relationship between m6A (N6-methyladenosine) modification and high expression of the ESCRT subunit was studied. Results VPS25 was upregulated in glioma tissues, which was correlated with poor prognosis in glioma patients. Furthermore, VPS25 knockdown inhibited the proliferation, blocked the cell cycle, and promoted apoptosis in glioma cells. Meanwhile, VPS25 induced a G0/G1 phase arrest of the cell cycle in glioma cells by directly mediating p21, CDK2, and cyclin E expression, and JAK-signal transducer and activator of transcription (STAT) activation. Finally, YTHDC1 inhibited glioma proliferation by reducing the expression of VPS25. Conclusion These results suggest that VPS25 is a promising prognostic indicator and a potential therapeutic target for glioma.

scholarly journals Polyomavirus large- and small-T relieve middle-T-induced cell cycle arrest in normal fibroblasts

1999 ◽  
Vol 80 (11) ◽  
pp. 2917-2921 ◽  
Author(s):  
Alain Marti ◽  
Kurt Ballmer-Hofer
Keyword(s):  
Cell Cycle ◽  
Growth Regulation ◽  
Cultured Cells ◽  
T Antigen ◽  
S Phase ◽  
Resting Cells ◽  
T Antigens ◽  
Cycle Arrest ◽  
Tumour Antigens

Papovavirus tumour antigens have been widely used to study cell growth regulation in cultured cells. We investigated the role of mouse polyomavirus T antigens, small-, middle- and large-T, in stimulating growth-arrested REF52 fibroblasts to enter the S phase. Microinjecting cells with cDNAs encoding the various T antigens showed: first, that middle-T expression blocked cell cycle stimulation by serum; second, that middle-T-arrested cells were released into the S phase upon coexpression of small-T; third, that expression of middle-T together with large-T committed resting cells to enter the cell cycle even in the absence of serum. Our data indicate that extensive cooperation among polyomavirus T antigens is essential for T antigen-mediated cell cycle stimulation in growth-arrested cells. In addition, the data suggest a new role for small-T in signalling to mitogenic pathways.

scholarly journals miR-192 Is Overexpressed and Promotes Cell Proliferation in Prostate Cancer

2018 ◽  
Vol 28 (2) ◽  
pp. 124-132 ◽  
Author(s):  
Zhong-Jun  Chen ◽  
You-Ji Yan ◽  
Hao Shen ◽  
Jia-Jie Zhou ◽  
Guang-Hua Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Bioinformatic Analysis ◽  
The Cancer Genome Atlas ◽  
Low Grade ◽  
Functional Roles ◽  
Normal Tissues ◽  
Cancer Genome Atlas

Objective: Prostate cancer (PCa) is one of the most prevalent types of cancer among men worldwide. The incidence of PCa is increasing in China. Therefore, there is an urgent need to identify novel diagnostic and prognostic markers for PCa to improve the treatment of the disease. Methods: The Cancer Genome Atlas (TCGA) and GEO database were used to analyze the expression of miR-192, and the relationship between miR-192 and the clinical features of patients with PCa. Cell cycle and cell proliferation assay were used to detect the functional roles of miR-192 in PCa. Bioinformatic analysis for miR-192–5p was performed using gene ontology and KEGG analysis. Results: By analyzing the dataset of TCGA, we found that miR-192 was overexpressed in PCa samples compared to normal tissues and was upregulated in high-grade PCa compared to low-grade PCa. We also observed that higher miR-192 expression was associated with a shorter biochemical recurrence-free survival time. Our results also demonstrated that miR-192 promoted PCa cell proliferation and cell cycle progression. Conclusion: These results suggest that miR-192 may be considered for use as a potential diagnostic and therapeutic target of PCa.

scholarly journals NDR1 functions as tumor suppressor in glioblastoma by phosphoralation of YAP

2021 ◽  
Author(s):  
Bin Chen ◽  
Bin Liu ◽  
Tao Yu ◽  
Yunfeng Han ◽  
Chao Wu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Tumor Suppressor ◽  
Hippo Pathway ◽  
Tumor Model ◽  
Hippo Signaling ◽  
Lower Survival Rate ◽  
Normal Tissues ◽  
Cycle Arrest

Abstract Purpose: The NDR1(Nuclear Dbf2-related) kinase is a member of the NDR/LATS family which was a supplementary of Hippo pathway. However, whether NDR1 could inhibit glioblastoma (GBM) growth by phosphorylating YAP remains unknown. Meanwhile, the role of NDR1 in GBM was not clear. The purpose of this study was to investigate the role of NDR1-YAP pathway in GBM. Materials and Methods: Bioinformation analysis and immunohistochemistry was performed to identify the expression of NDR1 in GBM. The effect of NDR1 on cell proliferation and cell cycle was analyzed utilizing cck-8, clone formation, immunofluorescence and flow cytometry respectively. In addition, the xenograft tumor model was established as well. Protein interaction was examined by Co-ip and immunofluorescence. Results: Bioinformation analysis and immunohistochemistry of our petients’ tumor tissues showed that expression of NDR1 in tumor tissue was relatively lower than that in normal tissues and was positively related to lower survival rate. NDR1 could markedly reduce the proliferation, colony formation of U87 and U251. Furthermore, the results of flow cytometry showed that NDR1 led to cell cycle arrest at the G1 phase. Tumor growth was also inhibited in xenograft nude mouse models in NDR1-OE group. Western blotting and immunofluorescence showed that NDR1 could integrate with and phophoralate YAP at S127 site. Meanwhile, NDR1 could mediate apopptosis process. Conclusion: In summary, our findings pointed out that NDR1 functions as a tumor suppressor in GBM. NDR1 was identified as a novel regulator of YAP, which give us a in depth comprehension in Hippo signaling pathway.

scholarly journals β-Catenin Regulation during the Cell Cycle: Implications in G2/M and Apoptosis

2003 ◽  
Vol 14 (7) ◽  
pp. 2844-2860 ◽  
Author(s):  
David Olmeda ◽  
Susanna Castel ◽  
Senén Vilaró ◽  
Amparo Cano
Keyword(s):  
Cell Cycle ◽  
S Phase ◽  
Epidermal Keratinocytes ◽  
Stable Form ◽  
Multifunctional Protein ◽  
Cycle Arrest ◽  
M Phase ◽  
Positive Modulator ◽  
G2 Cell Cycle Arrest

β-catenin is a multifunctional protein involved in cell-cell adhesion and Wnt signal transduction. β-Catenin signaling has been proposed to act as inducer of cell proliferation in different tumors. However, in some developmental contexts and cell systems β-catenin also acts as a positive modulator of apoptosis. To get additional insights into the role of β-Catenin in the regulation of the cell cycle and apoptosis, we have analyzed the levels and subcellular localization of endogenous β-catenin and its relation with adenomatous polyposis coli (APC) during the cell cycle in S-phase–synchronized epithelial cells. β-Catenin levels increase in S phase, reaching maximum accumulation at late G2/M and then abruptly decreasing as the cells enter into a new G1 phase. In parallel, an increased cytoplasmic and nuclear localization of β-catenin and APC is observed during S and G2 phases. In addition, strong colocalization of APC with centrosomes, but not β-catenin, is detected in M phase. Interestingly, overexpression of a stable form of β-catenin, or inhibition of endogenous β-catenin degradation, in epidermal keratinocyte cells induces a G2 cell cycle arrest and leads to apoptosis. These results support a role for β-catenin in the control of cell cycle and apoptosis at G2/M in normal and transformed epidermal keratinocytes.

MicroRNA-490-5P Targets CCND1 to Suppress Cellular Proliferation in Glioma Cells and Tissue Through Cell Cycle Arrest

2018 ◽  
Vol 15 (3) ◽  
pp. 246-255 ◽  
Author(s):  
Long Zhao ◽  
Xiaoping Tang ◽  
Renguo Luo ◽  
Jie Duan ◽  
Yuanchuan Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cellular Proliferation ◽  
Glioma Cells ◽  
Cycle Arrest

Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells

2020 ◽  
Vol 20 (6) ◽  
pp. 734-750
Author(s):  
Wallax A.S. Ferreira ◽  
Rommel R. Burbano ◽  
Claudia do Ó. Pessoa ◽  
Maria L. Harada ◽  
Bárbara do Nascimento Borges ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Glioma Cell ◽  
Molecular Mechanisms ◽  
Glioma Cells ◽  
Dependent Manner ◽  
M Cell ◽  
Trypan Blue Exclusion ◽  
Cycle Arrest

Background: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown. Objective: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines. Methods: The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect of pisosterol on the distribution of the cells in the cell cycle was performed by flow cytometry. The expression and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite sequencing PCR (BSP-PCR). Results: Here, it has been reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53. Conclusions: It has been, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggests that this compound might be a promising anticancer candidate for further investigation.

scholarly journals Role of Mis Localization of DNA Repair Factors in Cell Cycle Arrest

2019 ◽  
Vol 116 (3) ◽  
pp. 76a
Author(s):  
Manasvita Vashisth ◽  
Sangkyun Cho ◽  
Dennis Discher
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Cell Cycle Arrest ◽  
Cycle Arrest
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