Origin recognition complex subunit 1 regulates cell growth and metastasis in glioma by altering activation of ERK and JNK signaling pathway
Introduction
Glioma is considered the tumor with the highest malignancy in the central nervous system. It exhibits increased invasion and proliferation ability and accounts for about 40% of intracranial tumors, astrocytoma, ependymoma, mixed gliomas, and oligodendroglioma [1,2]. Glioma is classified into WHO grade I-IV and is located in the brain; hence, surgery to remove a brain tumor is difficult, and tumors recur easily after surgery [3]. In recent years, surgery, radiotherapy, and chemotherapy for brain cancer have advanced significantly; however, patients with gliomas have no obvious improvement in the five-year survival rate following these interventions [4]. The major cause of treatment failure is thought to be the invasive growth of gliomas and to tumor recurrence and metastasis [5]. Therefore, gene therapy has been developed as a new strategy for patients with gliomas and can deliver foreign genetic material into specific cell types; several types of therapies are possible, antibody-directed enzyme prodrug therapy (ADEPT), antitumor gene immunotherapy, anti-angiogenic therapy, and antisense gene therapy [6,7]. The identification, in the present study, of proteins that confer distinct invasive properties to cells may be of great value in developing novel therapeutic methods and understanding glioma invasion.
The initial step of DNA replication involves the origin recognition complex (ORC) in eukaryotes, consisting of Orc1/2/3/4/5/6. It was found in saccharomyces, with chromosomal replication origins [8]. It has been shown that ORC1/2/3/4/5/6 are expressed in different human tissues, e.g., lung [9], bones [10], kidney [11] and uterus [12]. Expression levels of ORC2-5 were not found to vary during the cell cycle [13]. However, ORC1 was found to be synthesized in the G1 phase and to be degraded in the S phase. These cell cycle-specific oscillations in the expression of ORC1 were closely associated with cell proliferation and cell cycle. It was also determined that ORC1 was responsible for cell cycle progression. Thus, ORC1 may be involved in cell proliferation, apoptosis, invasion, migration and other biological processes.
Section snippets
Database analysis
The mRNA expression data of glioblastoma cell lines were obtained from the Gene Expression Omnibus (GEO) profiles database (http://www.ncbi.nlm.nih.gov/geo/, GSE15824). The mRNA expression levels of 2893 differentially expressed genes (DEGs) were evaluated using the ‘limma’ package in R (https://www.r-project.org/). The expression levels were color coded and visualized using the heat map method. The significantly dysfunctional genes are shown in rows and the samples in columns. Red, black, and
Identification of differentially expressed genes
A total of 2893 DEGs, including 398 upregulated genes and 2495 downregulated genes (P < 0.05 and |logFC| > 1 as cutoff criterion), were identified from the GSE15824 dataset by using the ‘limma’ package in R (Fig. 1A). A volcano map was generated to assess the down-regulated and up-regulated mRNA (Fig. 1B).
Gene set enrichment analysis
GSEA was used to clarify the signaling pathways and functions of 2893 DEGs in glioblastoma cell lines. Our results showed that 35 DEGs (ATM, ENDOD1, TNFRSF10B, PIK3R3, PIK3R1, PPP3CB, IKBKG,
Discussion
Glioma is characterized by invasive growth leading to poor prognosis and low survival rate [23]. Thus, there is increased interest in finding an effective target for cancer treatment at the gene level. Based on bioinformatics analysis, a total of 35 DEGs from GEO data (GSE15824) were primarily enriched in apoptosis, cell cycle, and pathways involved in cancer by GSEA analysis (Fig. 1). GO analysis showed that CCNE2, CDK1, CDC6, CCND1, SKP2 and ORC1 were enriched in significant functions and
Funding
No funding was received.
Availability of data and materials
The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.
Ethics approval and consent to participate
All patients provided written informed consent, and the study conducted in accordance with the Declaration of Helsinki. Both clinical data and detailed follow-up data were obtained for all patients. All the specimens collected were handled according to the protocols approved by the Ethics Committee of Tumor Hospital of Jiangxi Province.
Authors' contributions
Wenmin Xiong and Chen Xie wrote the main manuscript and analyzed the data. Yang Qiu and Ziwei Tu performed the experiments. Qiaoying Gong designed the study. All authors read and approved the final manuscript.
Declaration of competing interest
The authors declare that they have no competing interests.
Acknowledgements
GSE15824 dataset (http://www.ncbi.nlm.nih.gov/geo/) was used to perform our study.
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Comparative analysis of alfalfa (Medicago sativa L.) seedling transcriptomes reveals genotype-specific drought tolerance mechanisms
2021, Plant Physiology and BiochemistryCitation Excerpt :It is interesting that some genes involved in cell division were differentially expressed only in DT. Among them, NF-kappa B is a nuclear factor-κB (NF-κB) that participates in the regulation of inflammatory enzymes and cytokines (Linghu et al., 2020), origin recognition complex subunit 1 (ORC1), which is reported to be closely associated with the cell cycle (Xiong et al., 2020), Mitotic-specific cyclin-B1 and NADPH can activate CDK1 throughout early mitosis (Levasseur et al., 2019), and CDK1 can ensure repression of macroautophagy during mitosis (Odle et al., 2020), Carbon degradation repression (Crc) can also indirectly inhibit the entry into cells of enzymes and transporters required for the translation of mRNAs encoding transcriptional regulators that drive the expression of genes whose products decompose specific substrates (Johnson et al., 2017). Dmc1 acts synergistically with the recombinase Rdh54 to mediate inter-homologue recombination during meiosis (Chi et al., 2009), and Dmc1 gene sequences are useful for resolution of the molecular phylogenetic relationships of tetraploid wheat (Tang et al., 2017), they were all up-regulated in DL, but few reports about the role of these cell cycle genes in drought tolerance, and additional research is needed to clarify their roles in alfalfa's drought response.