scholarly journals Minichromosome maintenance protein 2 correlates with the malignant status and regulates proliferation and cell cycle in lung squamous cell carcinoma

2018 ◽  
Vol Volume 11 ◽  
pp. 5025-5034 ◽  
Author(s):  
Wei Wu ◽  
Xianwei Wang ◽  
Changting Shan ◽  
Yong Li ◽  
Fengzhu Li
2019 ◽  
Author(s):  
Lei Zhang ◽  
Zhe Zhang ◽  
Zhenglun Yu

Abstract Background:Lung cancer (LC) is one of the most important and common malignant tumors, and its incidence and mortality are increasing annually. Lung squamous cell carcinoma (LUSC) is the common pathological type of lung cancer. A small part of biomarkers have been confirmed to be related to the prognosis and survival by data excavation. However, the moderate forecast effect of a single gene biomarker is not accurate. Thus, we aimed to identify new gene signatures to better predict Lung squamous cell carcinoma ( LU SC). Methods : Using the mRNA-mining approach, we performed mRNA expression profiling in large lung squamous cell carcinoma cohorts (n= from The Cancer Genome Atlas (TCGA) database. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis(GSVA) were accomplished, and connections between genes and cell cycle were found in the Cox proportional regression model. Results : We have confirmed a set of four genes (CDKN1A, CHEK2, E2F4 and RAD21) that were importantly associated with overall survival (OS) in the test series. Based on the research of the four-gene signature, the patients in the test series could be divided into high-risk and low-risk teams. Additionally, multivariate Cox regression analysis revealed that the prognostic power of the four-gene signature is independent of the clinical factors. Conclusion : Our study demonstrated the connections between the four-gene signature and cell cycle. Novel insights into the research mechanisms of cell cycle was also revealed regarding the biomarkers of a poor prognosis for lung squamous cell carcinoma patients.


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Yingji Chen ◽  
Ying Ji ◽  
Suo Liu ◽  
Yicai Liu ◽  
Wei Feng ◽  
...  

Abstract Background The roles of Polypyrimidine tract-binding protein 3 (PTBP3) in regulating lung squamous cell carcinoma (LUSC) cells progression is unclear. The aim of this study was to investigate the role of PTBP3 in LUSC. Methods Expression and survival analysis of PTBP3 was firstly investigated using TCGA datasets. Quantitative reverse transcription PCR and Western blot were performed to detect PTBP3 expression in clinical samples. Moreover, cell counting kit 8 (CCK-8) assays, colony formation assays and in vivo tumor formation assays were used to examine the effects of PTBP3 on LUSC cell proliferation. RNA-sequence and analysis explores pathways regulated by PTBP3.Flow cytology was used analyzed cell cycle. Cell cycle-related markers were analyzed by Western blot. Results PTBP3 was found to be overexpressed in LUSC tissues compared with normal tissues. High PTBP3 expression was significantly correlated with poor prognosis. In vitro and vivo experiments demonstrated that PTBP3 knockdown caused a significant decrease in the proliferation rate of cells. Bioinformatics analysis showed that PTBP3 involved in cell cycle pathway regulation in LUSC. Furthermore, PTBP3 knockdown arrested cell cycle progression at S phase via decreasing CDK2/Cyclin A2 complex. In addition, downregulation of PTBP3 significantly decreased the expression of CDC25A. Conclusions Our results suggest that PTBP3 regulated LUSC cell proliferation via cell cycle and might be a potential target for molecular therapy of LUSC.


2021 ◽  
Author(s):  
Baoxin Bai ◽  
Lingwei Wang ◽  
Zhiyuan Huang ◽  
Zhiwen Zhang ◽  
Ying Lu ◽  
...  

Abstract Purpose To study the functional role and prognosis of EIF4G1 in lung squamous cell carcinoma (LSCC). Methods The clinical relevance of EIF4G1 in LSCC was investigated following detection of the expression levels of EIF4G1 by immunohistochemical staining (IHC). The expression levels of EIF4G1, AKT2, p-AKT, mTOR, cyclin D1 and β-actin were detected by western blot analysis. The cell proliferation and colony formation assays were used to detect the cell proliferative ability; flow-cytometry was used to assess the cell cycle; an invasion assay was used to detect cell invasive ability and the real-time quantitative polymerase chain reaction (Q-PCR) assay was used to assess the expression levels of EIF4G1 and β-actin. The role of EIF4G1 was verified by xenograft models. These experimental methods were employed to assess the functional role of EIF4G1 in LSCC pathogenesis. Results EIF4G1 was overexpressed in LSCC tumor tissues (P < 0.05) compared with the corresponding expression noted in paired adjacent tissues and cells. The expression levels of EIF4G1 were dependent on age (P = 0.002) and clinical stage (I vs II vs III + IV) (P < 0.001). High expression of EIF4G1 (P = 0.008, HR = 2.277, 95% CI = 1.250–4.145) could be used to predict the overall survival of LSCC patients as determined by the Cox’s proportional hazard model. High expression of EIF4G1 exhibited a lower survival (LogRank = 7.167, P = 0.007) in LSCC. Downregulation of EIF4G1 significantly inhibited LSCC proliferation, invasion and cell cycle progression. Conclusion EIF4G1 promotes LSCC cell proliferation and may represent an indicator of prognosis in LSCC.


2020 ◽  
Author(s):  
Lei Zhang ◽  
Shize Yang ◽  
Zhenglun Yu

Abstract Purpose: Lung cancer (LC) is one of the most important and common malignant tumours, and its incidence and mortality are increasing annually. Lung squamous cell carcinoma (LUSC) is the most common pathological type of LC. A small number of biomarkers have been certified to be consistent with its survival and prognosis by data excavation. However, the moderate forecast effect of a single gene biomarker is not accurate. Thus, we planned to find new gene signatures to preferably predict LUSC. Methods: Using the mRNA mining method, we enforced mRNA expression analyzing in big LUSC cohorts (n=504) from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were enforced, and relations between genes and the cell cycle were got with the Cox proportional hazards regression model. Results: We confirmed a set of four genes (CDKN1A, CHEK2, E2F4 and RAD21) that was importantly related to overall survival (OS) in the test succession. Based on the four-gene signature, the patients were separated into high-risk and low-risk teams. Moreover ,multivariate Cox regression analysis showed that the prognostic value of the four-gene signature and clinical factors were mutual independent.Conclusion: Our research demonstrated connections between the four-gene signature and LUSC. Novel insights into mechanisms of the cell cycle were also revealed after determining that the biomarkers were related to a poor prognosis in LUSC patients.


Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1883
Author(s):  
Keiko Mizuno ◽  
Kengo Tanigawa ◽  
Shunsuke Misono ◽  
Takayuki Suetsugu ◽  
Hiroki Sanada ◽  
...  

Several recent studies have shown that both strands of certain miRNAs derived from miRNA duplexes are involved in cancer pathogenesis. Our own recent studies revealed that both strands of the miR-150 duplex act as tumor-suppressive miRNAs in lung adenocarcinoma (LUAD) through the targeting of several oncogenes. The aim of the study here was to further investigate the tumor-suppressive roles of miR-150-3p (the passenger strand) in lung squamous cell carcinoma (LUSQ) and its control of cancer-promoting genes in LUSQ cells. The downregulation of miR-150-3p in LUSQ tissues was confirmed by data in The Cancer Genome Atlas (TCGA). The ectopic expression of miR-150-3p attenuated cancer cell aggressive features, e.g., cell cycle arrest, migration and invasive abilities. Our target search strategy successfully identified a total of 49 putative targets that were listed as subjects of miR-150-3p regulation in LUSQ cells. Interestingly, among these targets, 17 genes were categorized as related to the “cell cycle” based on Gene Ontology (GO) classification, namely CENPA, CIT, CCNE1, CCNE2, TIMELESS, BUB1, MCM4, HELLS, SKA3, CDCA2, FANCD2, NUF2, E2F2, SUV39H2, CASC5, ZWILCH and CKAP2). Moreover, we show that the expression of HELLS (helicase, lymphoid specific) is directly controlled by miR-150-3p, and its expression promotes the malignant phenotype of LUSQ cells.


2021 ◽  
Vol 8 ◽  
Author(s):  
Huan Deng ◽  
Qingqing Hang ◽  
Dijian Shen ◽  
Hangjie Ying ◽  
Yibi Zhang ◽  
...  

Purpose: Progress related to the early detection and molecular targeted therapy of lung squamous cell carcinoma (LUSC) remains limited. The goal of our study was to identify key candidate indicators of LUSC.Methods: Three microarray datasets (GSE33532, GSE30219 and GSE19188) were applied to find differentially expressed genes (DEGs). Functional enrichment analyses of DEGs were carried out, and their protein-protein interaction (PPI) network was established. Hub genes were chosen from the PPI network according to their degree scores. Then, overall survival (OS) analyses of hub genes were carried out using Kaplan-Meier plotter, and their GSEA analyses were performed. Public databases were used to verify the expression patterns of CDK1 and CDC20. Furthermore, basic experiments were performed to verify our findings.Results: A total of 1,366 DEGs were identified, containing 669 downregulated and 697 upregulated DEGs. These DEGs were primarily enriched in cell cycle, chromosome centromeric region and nuclear division. Seventeen hub genes were selected from PPI network. Survival analyses demonstrated that CDK1 and CDC20 were closely associated with OS. GSEA analyses revealed that cell cycle, DNA replication, and mismatch repair were associated with CDK1 expression, while spliceosome, RNA degradation and cell cycle were correlated with CDC20 expression. Based on The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (THPA) databases, CDK1 and CDC20 were upregulated in LUSC at the mRNA and protein levels. Moreover, basic experiments also supported the obvious upregulation of CDK1 and CDC20 in LUSC.Conclusion: Our study suggests and validates that CDK1 and CDC20 are potential therapeutic targets and prognostic biomarkers of LUSC.


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