科研成果详情

题名CDK14/beta-catenin/TCF4/miR-26b positive feedback regulation modulating pancreatic cancer cell phenotypes in vitro and tumor growth in mice model in vivo
作者
发表日期2022-02
发表期刊JOURNAL OF GENE MEDICINE   影响因子和分区
语种英语
原始文献类型Article
关键词CDK14 miR-26b pancreatic ductal adenocarcinoma TCF4 Wnt/beta-catenin signaling
其他关键词BETA-CATENIN ; MICRORNAS ; PROLIFERATION ; INVASION ; WNT ; INHIBITION ; BIOGENESIS ; KNOCKDOWN ; COMPLEXES ; APOPTOSIS
摘要Introduction: Chemotherapy and radiotherapy have been reported to be basically ineffective for pancreatic ductal adenocarcinoma patients; thus, gene therapy might provide a novel approach. CDK14, a new oncogenic member of the CDK family involved in the pancreatic cancer cell response to gemcitabine treatment, has been reported to be regulated by microRNAs. In the present study, we aimed to investigate whether miR-26b regulated CDK14 expression to affect the phenotype of pancreatic cancer cells. Methods: Overexpression or knockdown of CDK14 or miR-26b was generated in pancreatic cancer cell lines and the function of CDK14 and miR-26b on cell phenotype and the Wnt signaling pathway was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, 5-ethynyl-2'-deoxyuridine and transwell assays, as well as a xenograft model and western blotting. The predicted binding site between the 3'-untranslated region of CDK14 and miR-26b, miR-26b promoter and TCF4 was verified by luciferase or chromatin immunoprecipitation assays. Results: CDK14 overexpression inhibited p-GSK3 beta, whereas it promoted p-LRP6, the nuclear translocation of beta-catenin and the transactivation of TCF4 transcription factor, thus promoting pancreatic cancer cell aggressiveness. miR-26b directly targeted CDK14 and inhibited CDK14 expression. In vitro and in vivo, miR-26b overexpression inhibited, and CDK14 overexpression promoted, cancer cell aggressiveness; CDK14 overexpression partially attenuated the miR-26b overexpression effects on cancer cells. The effects of miR-26b overexpression on tumor growth and the Wnt/beta-catenin/TCF4 signaling were partially reversed by CDK14 overexpression. TCF4 inhibited the expression of miR-26b by targeting its promoter region. Conclusions: CDK14, beta-catenin, TCF4 and miR-26b form a positive feedback regulation for modulating pancreatic cancer cell phenotypes in vitro and tumor growth in vivo.
资助项目Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province; Medical Health Science and Technology Project of Zhejiang Provincial Health Commission [2020KY636]; Wenzhou Science and Technology Bureau Project [Y2020155]
出版者WILEY
出版地HOBOKEN
ISSN1099-498X
EISSN1521-2254
卷号24期号:2页码:e3343.
DOI10.1002/jgm.3343
页数14
WOS类目Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental
WOS研究方向Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine
WOS记录号WOS:000731840700001
收录类别SCIE ; PUBMED ; SCOPUS
URL查看原文
PubMed ID33871149
SCOPUSEID2-s2.0-85121434738
通讯作者地址[Wu, Huanhuan]Department of Post-anesthetic ICU,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China
Scopus学科分类Molecular Medicine;Molecular Biology;Genetics;Drug Discovery;Genetics (clinical)
引用统计
被引频次:1[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符https://kms.wmu.edu.cn/handle/3ETUA0LF/13901
专题附属第一医院_肝胆外科
附属第一医院_胃肠外科
第二临床医学院、附属第二医院、育英儿童医院_麻醉学_ICU
通讯作者Wu, Huanhuan
作者单位
1.Department of Hepatobiliary Surgery,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China;
2.Department of Gastrointestinal Surgery,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China;
3.Department of Post-anesthetic ICU,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China
第一作者单位附属第一医院;  第一临床医学院(信息与工程学院)、附属第一医院
通讯作者单位附属第一医院;  第一临床医学院(信息与工程学院)、附属第一医院
第一作者的第一单位附属第一医院
推荐引用方式
GB/T 7714
Sun, Yunpeng,Wang, Pengfei,Zhang, Qiyu,et al. CDK14/beta-catenin/TCF4/miR-26b positive feedback regulation modulating pancreatic cancer cell phenotypes in vitro and tumor growth in mice model in vivo[J]. JOURNAL OF GENE MEDICINE,2022,24(2):e3343..
APA Sun, Yunpeng, Wang, Pengfei, Zhang, Qiyu, & Wu, Huanhuan. (2022). CDK14/beta-catenin/TCF4/miR-26b positive feedback regulation modulating pancreatic cancer cell phenotypes in vitro and tumor growth in mice model in vivo. JOURNAL OF GENE MEDICINE, 24(2), e3343..
MLA Sun, Yunpeng,et al."CDK14/beta-catenin/TCF4/miR-26b positive feedback regulation modulating pancreatic cancer cell phenotypes in vitro and tumor growth in mice model in vivo".JOURNAL OF GENE MEDICINE 24.2(2022):e3343..

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