CDK14/beta-catenin/TCF4/miR-26b positive feedback regulation modulating pancreatic cancer cell phenotypes in vitro and tumor growth in mice model in vivo

doi:10.1002/jgm.3343

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	Sun, Yunpeng1; Wang, Pengfei2; Zhang, Qiyu1; Wu, Huanhuan3
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
ISSN	1099-498X
EISSN	1521-2254
卷号	24 期号:2 页码:e3343.
DOI	10.1002/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 ID	33871149
SCOPUSEID	2-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..