{"title":"POLE2 silencing inhibits the progression of colorectal carcinoma cells via wnt signaling axis.","authors":"Weihua Jian, Lei Zhang","doi":"10.1080/15384047.2024.2392339","DOIUrl":null,"url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the most common malignant carcinoma worldwide. DNA polymerase epsilon 2, accessory subunit (POLE2) participates in DNA replication, repair, and cell cycle control, but its association with CRC development remains unclear. In the present study, the differentially expressed genes (DEGs) in CRC were screened from bioinformatics analysis based on GEO database. RT-qPCR was used to assess mRNA expression. CCK-8 and colony formation assays were applied for the evaluation of cell proliferation. Wound healing and transwell assays were used to detect cell migration and invasion. Protein levels were determined by Western blotting assay. We found that POLE2 was highly expressed in CRC tissues and cell lines. Inhibition of POLE2 suppressed the proliferation, migration and invasion of CRC cells. Mechanistically, Wnt/β-catenin signaling pathway was inactivated by inhibition of POLE2. Activation of Wnt/β-catenin pathway can reverse the function of POLE2 knockdown on CRC cells. <i>In vivo</i> studies demonstrated that POLE2 silencing could notably inhibit the growth of tumors, which was consistent with the results <i>in vitro</i>. In conclusion, we found POLE2 as a novel oncogene in CRC, providing a potential therapeutic or diagnostic target in CRC.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2392339"},"PeriodicalIF":4.4000,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340749/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Biology & Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/15384047.2024.2392339","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/18 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
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Abstract
Colorectal cancer (CRC) is one of the most common malignant carcinoma worldwide. DNA polymerase epsilon 2, accessory subunit (POLE2) participates in DNA replication, repair, and cell cycle control, but its association with CRC development remains unclear. In the present study, the differentially expressed genes (DEGs) in CRC were screened from bioinformatics analysis based on GEO database. RT-qPCR was used to assess mRNA expression. CCK-8 and colony formation assays were applied for the evaluation of cell proliferation. Wound healing and transwell assays were used to detect cell migration and invasion. Protein levels were determined by Western blotting assay. We found that POLE2 was highly expressed in CRC tissues and cell lines. Inhibition of POLE2 suppressed the proliferation, migration and invasion of CRC cells. Mechanistically, Wnt/β-catenin signaling pathway was inactivated by inhibition of POLE2. Activation of Wnt/β-catenin pathway can reverse the function of POLE2 knockdown on CRC cells. In vivo studies demonstrated that POLE2 silencing could notably inhibit the growth of tumors, which was consistent with the results in vitro. In conclusion, we found POLE2 as a novel oncogene in CRC, providing a potential therapeutic or diagnostic target in CRC.
期刊介绍：
Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.
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