miR-196b-5p-mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer

doi:10.1073/pnas.1917531117

科研成果详情

题名	miR-196b-5p-mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer
作者	Liang, Guang1,2; Meng, Wei 3; Huang, Xiangjie 1; Zhu, Wangyu4; Yin, Changtian 1; Wang, Canwei 1,2; Fassan, Matteo 5; Yu, Yun1; Kudo, Masahisa 6; Xiao, Sisi 1,7; Zhao, Chengguang1; Zou, Peng1; Wang, Yumin7; Li, Xiaokun1; Croce, Carlo M.6; Cui, Ri1,2,6
发表日期	2020-02-25
发表期刊	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 影响因子和分区
语种	英语
原始文献类型	Article
关键词	QKI miR-196b NSCLC GATA6 TSPAN12
其他关键词	RNA-BINDING PROTEIN ; MICRORNA THERAPEUTICS ; GROWTH ; MIR-196B ; DIFFERENTIATION ; MIGRATION ; SIGNAL ; QKI-5
摘要	Lung cancer is the leading cause of cancer-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for over 80% of lung cancer cases. The RNA binding protein, QKI, belongs to the STAR family and plays tumor-suppressive functions in NSCLC. QKI-5 is a major isoform of QKIs and is predominantly expressed in NSCLC. However, the underlying mechanisms of QKI-5 in NSCLC progression remain unclear. We found that QKI-5 regulated microRNA (miRNA), miR-196b-5p, and its expression was significantly upregulated in NSCLC tissues. Up-regulated miR-196b-5p promotes lung cancer cell migration, proliferation, and cell cycle through directly targeting the tumor suppressors, GATA6 and TSPAN12. Both GATA6 and TSPAN12 expressions were down-regulated in NSCLC patient tissue samples and were negatively correlated with miR196b-5p expression. Mouse xenograft models demonstrated that miR-196b-5p functions as a potent onco-miRNA, whereas TSPAN12 functions as a tumor suppressor in NSCLC in vivo. QKI-5 bound to miR-196b-5p and influenced its stability, resulting in up-regulated miR-196b-5p expression in NSCLC. Further analysis showed that hypomethylation in the promoter region enhanced miR-196b-5p expression in NSCLC. Our findings indicate that QKI-5 may exhibit novel anticancer mechanisms by regulating miRNA in NSCLC, and targeting the QKI5 similar to miR-196b-5p similar to GATA6/TSPAN12 pathway may enable effectively treating some NSCLCs.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672305]; National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [1R35CA197706-01]
出版者	NATL ACAD SCIENCES
出版地	WASHINGTON
ISSN	0027-8424
EISSN	1091-6490
卷号	117 期号:8 页码:4347-4357
DOI	10.1073/pnas.1917531117
页数	11
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
WOS记录号	WOS:000516771500061
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	32041891
PMC记录号	PMC7049122
SCOPUSEID	2-s2.0-85080074624
自科自定义期刊分类	T3(A)类
通讯作者地址	[Cui, Ri]Cancer and Anticancer Drug Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China
Scopus学科分类	Multidisciplinary
引用统计	被引频次：53[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/8821
专题	药学院（分析测试中心）附属第一医院其他_附属乐清医院（乐清市人民医院）其他_附属舟山医院（舟山医院）
通讯作者	Cui, Ri
作者单位	1.Cancer and Anticancer Drug Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China; 2.Affiliated Yueqing Hospital,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China; 3.Department of Radiation Oncology,Comprehensive Cancer Center,Ohio State University,Columbus,43210,United States; 4.Affiliated Zhoushan Hospital,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China; 5.Department of Medicine,University of Padua,Padua,35128,Italy; 6.Department of Cancer Biology and Genetics,Comprehensive Cancer Center,Ohio State University,Columbus,43210,United States; 7.First Affiliated Hospital,Wenzhou Medical University,Wenzhou, Zhejiang,325000,China
第一作者单位	药学院（分析测试中心）; 附属乐清医院（乐清市人民医院）
通讯作者单位	药学院（分析测试中心）
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Liang, Guang,Meng, Wei,Huang, Xiangjie,et al. miR-196b-5p-mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2020,117(8):4347-4357.
APA	Liang, Guang., Meng, Wei., Huang, Xiangjie., Zhu, Wangyu., Yin, Changtian., ... & Cui, Ri. (2020). miR-196b-5p-mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 117(8), 4347-4357.
MLA	Liang, Guang,et al."miR-196b-5p-mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 117.8(2020):4347-4357.