scholarly journals RNA-binding motif protein 5 inhibits the proliferation of cigarette smoke-transformed BEAS-2B cells through cell cycle arrest and apoptosis

2016 ◽  
Vol 35 (4) ◽  
pp. 2315-2327 ◽  
Author(s):  
XUE-JIAO LV ◽  
YAN-WEI DU ◽  
YU-QIU HAO ◽  
ZHEN-ZHONG SU ◽  
LIN ZHANG ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cigarette Smoke ◽  
Rna Binding ◽  
Binding Motif ◽  
Cycle Arrest

scholarly journals The RNA-binding protein SART3 promotes miR-34a biogenesis and G1 cell cycle arrest in lung cancer cells

2019 ◽  
Vol 294 (46) ◽  
pp. 17188-17196 ◽  
Author(s):  
Emily J. Sherman ◽  
Dylan C. Mitchell ◽  
Amanda L. Garner
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Mirna Biogenesis ◽  
Regulatory Pathways ◽  
Cycle Arrest

MicroRNAs (miRNAs or miRs) are small, noncoding RNAs that are implicated in the regulation of most biological processes. Global miRNA biogenesis is altered in many cancers, and RNA-binding proteins play a role in miRNA biogenesis, presenting a promising avenue for targeting miRNA dysregulation in diseases. miR-34a exhibits tumor-suppressive activities by targeting cell cycle regulators CDK4/6 and anti-apoptotic factor BCL-2, among other regulatory pathways such as Wnt, TGF-β, and Notch signaling. Many cancers exhibit down-regulation or loss of miR-34a, and synthetic miR-34a supplementation has been shown to inhibit tumor growth in vivo. However, the post-transcriptional mechanisms that cause miR-34a loss in cancer are not entirely understood. Here, using a proteomics-mediated approach in non-small-cell lung cancer (NSCLC) cells, we identified squamous cell carcinoma antigen recognized by T-cells 3 (SART3) as a putative pre-miR-34a–binding protein. SART3 is a spliceosome recycling factor and nuclear RNA-binding protein with no previously reported role in miRNA regulation. We found that SART3 binds pre-miR-34a with higher specificity than pre-let-7d (used as a negative control) and elucidated a new functional role for SART3 in NSCLC cells. SART3 overexpression increased miR-34a levels, down-regulated the miR-34a target genes CDK4/6, and caused a cell cycle arrest in the G1 phase. In vitro binding experiments revealed that the RNA-recognition motifs within the SART3 sequence are responsible for selective pre-miR-34a binding. Our results provide evidence for a significant role of SART3 in miR-34a biogenesis and cell cycle progression in NSCLC cells.

Cigarette smoke is an endothelial stressor and leads to cell cycle arrest

2008 ◽  
Vol 201 (2) ◽  
pp. 298-305 ◽  
Author(s):  
Blair Henderson ◽  
Adam Csordas ◽  
Aleksandar Backovic ◽  
Michaela Kind ◽  
David Bernhard ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cigarette Smoke ◽  
Cycle Arrest

scholarly journals Downregulation of Lysosome-Associated Membrane Protein-2A Contributes to the Pathogenesis of COPD

2021 ◽  
Author(s):  
Yun-Jeong Jeong ◽  
Kyoung-Hee Lee ◽  
Jisu Woo ◽  
Ji Yeon Kim ◽  
Chang-Hoon Lee ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Epithelial Cells ◽  
Membrane Protein ◽  
Cell Cycle Arrest ◽  
Cigarette Smoke ◽  
Cyclin B1 ◽  
Knock Down ◽  
Cycle Arrest ◽  
Copd Patients ◽  
Never Smokers

Abstract Background: Macroautophagy plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD), but the role of chaperone-mediated autophagy (CMA) has not been investigated. We investigated if and how CMA is involved in the pathogenesis of COPD. Methods: We measured the level of lysosome-associated membrane protein-2A (LAMP-2A), which is a critical component of CMA that functions as a receptor for cytosolic substrate proteins, in total lung tissues and primary human bronchial epithelial cells (HBEC) from healthy never smokers, healthy smokers, and COPD patients. We assessed the effects of LAMP-2A knock-down on cigarette smoke extract (CSE)-induced aging, cell cycle arrest, and apoptosis in BEAS-2B cells and the expression levels of apoptosis hallmarks in primary HBECs and lung tissue sections.Results: We found that the protein levels of LAMP-2A in lung homogenates and primary HBECs from smokers and COPD patients were lower than those from never smokers. In addition, its level in primary HBECs was negatively correlated with years of smoking. CSE caused degradation of LAMP-2A protein via the lysosomal pathway by activating macroautophagy. Knock-down of LAMP-2A markedly enhanced CSE-induced expression of senescence markers such as p16, p21, and p27, G2/M cell cycle arrest, up-regulation of cyclin B1, and apoptosis in BEAS-2B cells. Apoptosis was increased in CSE-treated primary HBECs and in lung tissues from smokers and COPD patients.Conclusions: Cigarette smoke-induced down-regulation of LAMP-2A is involved in the pathogenesis of COPD by accelerating aging and apoptosis of lung epithelial cells.

scholarly journals MCG10, a Novel p53 Target Gene That Encodes a KH Domain RNA-Binding Protein, Is Capable of Inducing Apoptosis and Cell Cycle Arrest in G2-M

2000 ◽  
Vol 20 (15) ◽  
pp. 5602-5618 ◽  
Author(s):  
Jianhui Zhu ◽  
Xinbin Chen
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Target Gene ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Wild Type ◽  
Cycle Arrest ◽  
Kh Domain ◽  
P53 Target Gene

ABSTRACT p53, a tumor suppressor, inhibits cell proliferation by inducing cellular genes involved in the regulation of the cell cycle.MCG10, a novel cellular p53 target gene, was identified in a cDNA subtraction assay with mRNA isolated from a p53-producing cell line. MCG10 can be induced by wild-type but not mutant p53 and by DNA damage via two potential p53-responsive elements in the promoter of the MCG10 gene. The MCG10 gene contains 10 exons and is located at chromosome 3p21, a region highly susceptible to aberrant chromosomal rearrangements and deletions in human neoplasia. The MCG10 gene locus encodes at least two alternatively spliced transcripts, MCG10 and MCG10as. The MCG10 and MCG10as proteins contain two domains homologous to the heterogeneous nuclear ribonucleoprotein K homology (KH) domain. By generating cell lines that inducibly express either wild-type or mutated forms of MCG10 and MCG10as, we found that MCG10 and MCG10as can suppress cell proliferation by inducing apoptosis and cell cycle arrest in G2-M. In addition, we found that MCG10 and MCG10as, through their KH domains, can bind poly(C) and that their RNA-binding activity is necessary for inducing apoptosis and cell cycle arrest. Furthermore, we found that the level of the poly(C) binding MCG10 protein is increased in cells treated with the DNA-damaging agent camptothecin in a p53-dependent manner. These results suggest that the MCG10 RNA-binding protein is a potential mediator of p53 tumor suppression.

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