Alternate Polyadenylation in Rodent Cells Results in Two Differentially Expressed Cyclin B1 mRNAs

1994 ◽  
Vol 202 (2) ◽  
pp. 908-914 ◽  
Author(s):  
A. Maity ◽  
W.G. Mckenna ◽  
D.A. Markiewicz ◽  
A. Kunig ◽  
R.J. Muschel
2021 ◽  
Vol 10 (9) ◽  
pp. 558-570
Author(s):  
Chuan Li ◽  
Zhi Peng ◽  
You Zhou ◽  
Yongyue Su ◽  
Pengfei Bu ◽  
...  

Aims Developmental dysplasia of the hip (DDH) is a complex musculoskeletal disease that occurs mostly in children. This study aimed to investigate the molecular changes in the hip joint capsule of patients with DDH. Methods High-throughput sequencing was used to identify genes that were differentially expressed in hip joint capsules between healthy controls and DDH patients. Biological assays including cell cycle, viability, apoptosis, immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were performed to determine the roles of the differentially expressed genes in DDH pathology. Results More than 1,000 genes were differentially expressed in hip joint capsules between healthy controls and DDH. Both gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that extracellular matrix (ECM) modifications, muscle system processes, and cell proliferation were markedly influenced by the differentially expressed genes. Expression of Collagen Type I Alpha 1 Chain (COL1A1), COL3A1, matrix metalloproteinase-1 (MMP1), MMP3, MMP9, and MMP13 was downregulated in DDH, with the loss of collagen fibres in the joint capsule. Expression of transforming growth factor beta 1 (TGF-β1) was downregulated, while that of TGF-β2, Mothers against decapentaplegic homolog 3 (SMAD3), and WNT11 were upregulated in DDH, and alpha smooth muscle actin (αSMA), a key myofibroblast marker, showed marginal increase. In vitro studies showed that fibroblast proliferation was suppressed in DDH, which was associated with cell cycle arrest in G0/G1 and G2/M phases. Cell cycle regulators including Cyclin B1 (CCNB1), Cyclin E2 (CCNE2), Cyclin A2 (CCNA2), Cyclin-dependent kinase 1 (CDK1), E2F1, cell division cycle 6 (CDC6), and CDC7 were downregulated in DDH. Conclusion DDH is associated with the loss of collagen fibres and fibroblasts, which may cause loose joint capsule formation. However, the degree of differentiation of fibroblasts to myofibroblasts needs further study. Cite this article: Bone Joint Res 2021;10(9):558–570.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yuan Xia ◽  
Xulong Zhang ◽  
Dejun Sun ◽  
Yumin Gao ◽  
Xiaoe Zhang ◽  
...  

Abstract Background This study aims to investigate the effects of water soluble particulate matter (WSPM) on the viability and protein expression profile of human lung adenocarcinoma cell A549 in the Bayou Obo rare earth mining area, and explore the influence of WSPM on the A549 cell cycle. Results It was found that WSPM can inhibit the viability of A549 cells and induce cell arrest in the G2/M phase. Compared with controls, exposure to WSPM10 and WSPM2.5 induced 134 and 116 proteins to be differentially expressed in A549 cells, respectively. In addition, 33 and 31 differentially expressed proteins were further confirmed, and was consistent with the proteomic analysis. The most prominent enrichment in ribosome-associated proteins were presented. When RPL6, RPL13, or RPL18A gene expression was inhibited, A549 cells were arrested in the G1 phase, affecting the expression of Cyclin D1, p21, RB1, Cyclin A2, Cyclin B1, CDC25A, CDK2, CHEK2 and E2F1. Furthermore, the La3+, Ce3+, Nd3+ and F- in WSPM also inhibited the viability of A549 cells. After 24 h of exposure to 2 mM of NaF, A549 cells were also arrested in the G2/M phase, while the other three compounds did not have this effect. These four compounds affected the cell cycle regulatory factors in A549 cells, mainly focusing on effecting the expression of CDK2, CDK4, RB1, ATM, TP53 and MDM2 genes. These results are consistent with the those from WSPM exposure. Conclusions These results revealed that WSPM from rare earth mines decreased the viability of A549 cells, and induced cell cycle G2/M phase arrest, and even apoptosis, which may be independent of the NF-κB/MYD88 pathway, and be perceived by the TLR4 receptor. The dysfunction of the cell cycle is correlated to the down-expression of ribosomal proteins (RPs). However, it is not the direct reason for the A549 cell arrest in the G2/M phase. La3+, Ce3+, and F- are probably the main toxic substances in WSPM, and may be regulate the A549 cell cycle by affecting the expression of genes, such as MDM2, RB1, ATM, TP53, E2F1, CDK2 and CDK4. These results indicate the importance for further research into the relationship between APM and lung cancer.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jieling Li ◽  
Liyuan Zhou ◽  
Ying Liu ◽  
Lingzhi Yang ◽  
Dayi Jiang ◽  
...  

Colon cancer is a common malignancy of the digestive tract with high morbidity and mortality. There is an urgent need to identify effective biomarkers for the early diagnosis of colon cancer and to prolong patient survival. Cyclins are a family of proteins that directly participate in the cell cycle and are associated with many types of tumors, but the role and regulatory mechanism of most cyclin family members in colon cancer remain unclear. Here, we provide a systematic and comprehensive study of cyclin family gene expression and their potential roles in colon cancer. Pan-cancer analysis revealed that cyclin genes were most differentially expressed in colon adenocarcinoma. Among the four datasets of colon cancer from The Cancer Genome Atlas and the Gene Expression Omnibus, six cyclin genes (CCNA2, CCNB1, CCND1, CCNE1, CCNF, and CCNJL) were differentially expressed between normal and tumor tissues. Four of them (CCNA2, CCNB1, CCNE1, and CCNF) were notably elevated in the early TNM stages and significantly correlated with overall survival. Meanwhile, the expression of CCNA2 and CCNB1 was positively correlated with tumor-killing immune cells, such as CD8+ T cells.The copy numbers of CCNA2, CCNB1, CCND1, CCNE1, and CCNF was positively related to gene expression. The methylation levels of CCNB1 were lower in tumor tissues than in normal tissues and were negatively correlated with gene expression. The receiver operating characteristic curves indicated that the gene expression of 24 cyclins had higher predictive accuracy than the TNM stage. Pathway analysis showed that cyclin genes were tightly associated with apoptosis, the cell cycle, hormone ER, the RAS/MAPK pathway, mismatch repair, mTORC1 signaling, KRAS signaling, Akt, and TGFB in colon cancer. Weighted gene co-expression network analysis suggested that cyclin genes were closely linked to CDK1, BIRC5, PLK1, and BCL2L12. At the protein level, Cyclin A2 and Cyclin B1 were also expressed higher in colon adenocarcinoma tissues. In addition, cyclin genes were highly related to the drug sensitivity of some FDA-approved drugs, such as MEK and EGFR inhibitors, which might provide guidance for clinical treatment. In conclusion, cyclin genes are promising biomarkers for the diagnosis and prognosis of colon cancer.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18110-e18110
Author(s):  
Kidong Kim ◽  
Suhyun Hwangbo ◽  
Taesung Park ◽  
Hyojin Kim ◽  
Yong Beom Kim ◽  
...  

e18110 Background: Requirement of DNA sequencing to diagnose POLE group is a barrier for adoption of molecular subtyping in endometrial cancer. We aimed to identify clinicopathologic and protein markers distinguishing POLE and copy-number (CN) low group in endometrial cancer. Methods: Ninety-one samples (POLE: 15, CN low 76) classified as POLE or CN low groups by integrative clustering were selected from The Cancer Genome Atlas endometrial cancer dataset. Clinicopathologic variables and normalized reverse phase protein array expression data were extracted. We first selected clinicopathologic variables associated with group (POLE vs CN low) via univariate analysis. Then, we identified protein makers using the logistic regression model with significant clinicopathologic variables as adjusting covariates. The differentially expressed proteins were selected based on q-value of the false discovery rate for multiple comparison. With various q-value cut-off ( < 5%, 10%, 20%), several logistic models including differentially expressed markers were constructed by stepwise selection method using the area under curve (AUC) from 5-fold cross-validation (CV). Results: Among clinicopathologic variables, body mass index (BMI) and tumor grade were associated with group (p = 0.02 and p < 0.01, respectively). Being adjusted for BMI and tumor grade, 5 proteins were associated with group in q-value cut-off of < 5%. The model including clinicopathologic variables and 5 proteins identified BMI, Cyclin B1, Caspase 8, and XBP1 as markers distinguishing POLE and CN low groups. The mean of CV AUC, sensitivity and specificity of the selected model were 0.97, 0.97, and 0.60, respectively. Conclusions: BMI and expression levels of Cyclin B1, Caspase 8, XBP1 are candidate markers distinguishing POLE and CN low group. A further validation study using immunohistochemical staining is necessary to facilitate the adoption of molecular subtyping as daily practice.


2005 ◽  
Vol 173 (4S) ◽  
pp. 178-178
Author(s):  
Stephen O. Ikuerowo ◽  
Stefan A. Machtens ◽  
Markus A. Kuczyk ◽  
Udo Jonas ◽  
Juergen Serth

2009 ◽  
Vol 47 (01) ◽  
Author(s):  
I Strack ◽  
M Scheffler ◽  
S Schievenbusch ◽  
J Riemer ◽  
A Noetel ◽  
...  

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