Downregulation of ubiquitin inhibits the proliferation and radioresistance of non-small cell lung cancer cells in vitro and in vivo

Tang, Yiting; Geng, Yangyang; Luo, Judong; Shen, Wenhao; Zhu, Wei; Meng, Cuicui; Li, Ming; Zhou, Xifa; Zhang, Shuyu; Cao, Jianping

doi:10.1038/srep09476

Cited by 62 publications

(65 citation statements)

References 51 publications

(57 reference statements)

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“…For instance, the expression of enolase 1, cytokeratin 18 and HSPs in tumors may be valuable diagnostic and therapeutic targets. Overexpression of ubiquitin C in this study corroborates a previous research that found down-regulation of ubiquitin C suppresses growth and increases the radio-sensitivity of human nonsmall cell lung carcinoma cells (18). Interestingly, three of the shared genes are related to the HSP family, suggesting their Original Article possible involvement in cancer progression.…”

Section: Discussionsupporting

confidence: 89%

A Comparative Analysis of Gene Expression Profile in Liver and Esophageal Cancer using Expressed Sequence Tags

Ramezani

Shamsabadi

Oladnabi

2019

jcbr

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Background and objectives: Liver and esophageal cancers are common among the Iranian population. This study aims to explore the common up-regulated genes in liver and esophageal cancer tissues using expressed sequence tags (ESTs) and to identify the role of key genes in cancer development. Methods: EST profiles of protein-coding genes in normal and cancerous hepatic and esophageal tissues were extracted from the UniGene database. Genes with > 1500 transcripts per million were selected as highly expressed. The cancer to normal ratio of up-regulated genes was calculated. The shared overexpressed genes between liver and esophageal cancer tissues were determined. Finally, functional classification and pathway analysis were performed on the genes using the STRING and Enrichr databases. Results: Of 17,242 genes, 53 and 26 genes were overexpressed in the liver and esophageal cancer tissues, respectively. Nine up-regulated genes (APLP2, EEF1G, ENO1, HSP90AA1, HSP90AB1, HSPA8, KRT18, RPL4 and UBC) were shared between the two cancer tissues, which were involved in cell cycle progression through G2/M checkpoint, G1/S transition and DNA replication. They were also involved in the vascular endothelial growth factor, hypoxia-inducible factor 1 and estrogen signal pathways as well as the Toll-like receptor cascade. Conclusion: Based on the results, the identically up-regulated genes and underlying molecular mechanisms implicated in both cancers could be valuable targets for diagnosis and treatment of cancer.

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Section: Discussionsupporting

confidence: 89%

A Comparative Analysis of Gene Expression Profile in Liver and Esophageal Cancer using Expressed Sequence Tags

Ramezani

Shamsabadi

Oladnabi

2019

jcbr

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“…After 24 h, the cells were transfected with 50 nM of SPINK13-overexpressing vector (pcDNA-SPINK13), control vector (pcDNA3.1), siRNA-SPINK13 (si-SPINK13) or siRNA-NC (si-NC) and allowed to grow for another 48 h. Cell proliferation was measured using the MTT assay as reported previously [18]. The OD value was represented as the viability index.…”

Section: Methodsmentioning

confidence: 99%

Downregulation of SPINK13 Promotes Metastasis by Regulating uPA in Ovarian Cancer Cells

Cai

Zhang

Dong

et al. 2018

Cell Physiol Biochem

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Background/Aims: Ovarian cancer (OC) is the fifth leading cause of cancer-related death in women, and it is difficult to diagnose at an early stage. The purpose of this study was to explore the prognostic biological markers of OC. Methods: Univariate Cox regression analysis was used to identify genes related to OC prognosis from the Cancer Genome Atlas(TCGA) database. Immunohistochemistry was used to analyse the level of SPINK13 in OC and normal tissues. Cell proliferation, apoptosis and invasion were performed using MTT assay, flow cytometric analysis and Transwell assay, respectively. Results: We identified the Kazal-type serine protease inhibitor-13 (SPINK13) gene related to OC prognosis from the Cancer Genome Atlas (TCGA) database by univariate Cox regression analysis. Overexpression of SPINK13 was associated with higher overall survival rate in OC patients. Immunohistochemistry showed that the level of SPINK13 protein was significantly lower in OC tissues than in normal tissues (P < 0.05).In vitro experiments showed that the overexpression of SPINK13 inhibited cellular proliferation and promoted apoptosis. Moreover, SPINK13 inhibited cell migration and epithelial to mesenchymal transition (EMT). SPINK13 was found to inhibit the expression of urokinase-type plasminogen activator (uPA), while recombinant uPA protein could reverse the inhibitory effect of SPINK13 on OC metastasis. Conclusion: These results indicate that SPINK13 functions as a tumour suppressor. The role of SPINK13 in cellular proliferation, apoptosis and migration is uPA dependent, and SPINK13 may be used as a potential biomarker for diagnosis and targeted therapy in OC.

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“…Among the 10 hub DMGs revealed in our analysis, six (STAT3, PTPN6, SYK, STAT5B,and XPO1, and ABL1) had known CLL relevance; hence, our results corroborated previous data. The remaining four (UBC, GRB2, CREBBP, and GAB2) have never been reported in previous CLL studies [38][39][40][41][42][43][44][45][46][47][48] . UBC represents a ubiquitin gene (ubiquitin C) and has been described in cancers infrequently.…”

Section: Discussionmentioning

confidence: 73%

Novel genes exhibiting DNA methylation alterations in Korean patients with chronic lymphocytic leukaemia: a methyl-CpG-binding domain sequencing study

Kim

Lee

Zang

et al. 2020

Sci Rep

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Chronic lymphocytic leukaemia (CLL) exhibits differences between Asians and Caucasians in terms of incidence rate, age at onset, immunophenotype, and genetic profile. We performed genomewide methylation profiling of CLL in an Asian cohort for the first time. Eight Korean patients without somatic immunoglobulin heavy chain gene hypermutations underwent methyl-cpG-binding domain sequencing (MBD-seq), as did five control subjects. Gene Ontology, pathway analysis, and networkbased prioritization of differentially methylated genes were also performed. More regions were hypomethylated (2,062 windows) than were hypermethylated (777 windows). Promoters contained the highest proportion of differentially methylated regions (0.08%), while distal intergenic and intron regions contained the largest number of differentially methylated regions. Protein-coding genes were the most abundant, followed by long noncoding and short noncoding genes. The most significantly over-represented signalling pathways in the differentially methylated gene list included immune/ cancer-related pathways and B-cell receptor signalling. Among the top 10 hub genes identified via network-based prioritization, four (UBC, GRB2, CREBBP, and GAB2) had no known relevance to cLL, while the other six (STAT3, PTPN6, SYK, STAT5B, XPO1, and ABL1) have previously been linked to cLL in Caucasians. As such, our analysis identified four novel candidate genes of potential significance to Asian patients with CLL. Chronic lymphocytic leukaemia (CLL) is characterized by the co-expression of CD5 and CD23 in monomorphic small B-cells; it is the most common leukaemia among adults in Western countries, especially the elderly 1. CLL among Asians differs from that among Caucasians in terms of the incidence rate, median age at onset, phenotype, and the genetic profile. The incidence rates per 100,000 person-years in Korea and Japan are 0.04 and 0.48, respectively, but the rate is 3.83 in Western countries 2. The median age at initial CLL diagnosis is 61 and 70 years among Asians and Caucasians, respectively 2. A single-institution study in South Korea found that 56% of patients had an atypical immunophenotype with high frequencies of FMC7 positivity and strong CD22 positivity 3. A Chinese study showed that TP53 mutations are more common in Chinese patients with CLL than in Caucasian patients, whereas SF3B1 mutations are less common 4. Furthermore, a Korean study found that the frequencies of mutations in ATM, TP53, KLHL6, BCOR, and CDKN2A tend to be higher in Koreans than in Caucasians, while those in SF3B1, NOTCH1, CHD2, and POT1 tend to be lower 2. DNA methylation directly impacts human genome function, and multiple studies have demonstrated the existence of aberrant epigenetic changes that play important roles in tumour initiation and progression in Western patients with CLL 5-8. Recent advances in high-throughput techniques have enabled genome-wide methylation profiling in Caucasians with CLL. For example, an array study identified methylation in seven known or candidate

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Downregulation of ubiquitin inhibits the proliferation and radioresistance of non-small cell lung cancer cells in vitro and in vivo

Cited by 62 publications

References 51 publications

A Comparative Analysis of Gene Expression Profile in Liver and Esophageal Cancer using Expressed Sequence Tags

A Comparative Analysis of Gene Expression Profile in Liver and Esophageal Cancer using Expressed Sequence Tags

Downregulation of SPINK13 Promotes Metastasis by Regulating uPA in Ovarian Cancer Cells

Novel genes exhibiting DNA methylation alterations in Korean patients with chronic lymphocytic leukaemia: a methyl-CpG-binding domain sequencing study

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