KSRP suppresses cell invasion and metastasis through miR-23a-mediated EGR3 mRNA degradation in non-small cell lung cancer

Ming Hsien Chien, Wei Jiunn Lee, Yi Chieh Yang, Yin Lin Li, Bo Rong Chen, Tsu Yao Cheng, Pei Wen Yang, Ming Yang Wang, Yi Hua Jan, Yen Kuang Lin, Jang Ming Lee, Michael Hsiao, Jin Shing Chen, Kuo Tai Hua

研究成果: 雜誌貢獻文章

5 引文 (Scopus)

摘要

KH-type splicing regulatory protein (KSRP) is a single-strand RNA binding protein which regulates mRNA stability either by binding to AU-rich elements (AREs) of mRNA 3′UTR or by facilitating miRNA biogenesis to target mRNA. Unlike its well-characterized function at the molecular level in maintaining RNA homeostasis, the role of KSRP in cancer progression remains largely unknown. Here we investigate the role of KSRP in non-small cell lung cancer (NSCLC). We first examined KSRP expression by immunohistochemistry in a cohort containing 196 NSCLC patients and observed a strong positive correlation between KSRP expression and survival of NSCLC patients. Multivariate analysis further identified KSRP as an independent prognostic factor. Manipulating KSRP expression significantly affected in vitro cell mobility and in vivo metastatic ability of NSCLC cells. Microarray analysis identified an ARE-containing gene, EGR3, as a downstream effector of KSRP in NSCLC. Interestingly, we found that KSRP decreased EGR3 mRNA stability in an ARE-independent manner. By screening KSRP-regulated miRNAs in NSCLC cells, we further found that miR-23a directly binds to EGR3 3′UTR, reducing EGR3 expression and thereby inhibiting NSCLC cell mobility. Our findings implicate a targetable KSRP/miR-23a/EGR3 signaling axis in advanced tumor phenotypes.

原文英語
頁(從 - 到)1013-1024
頁數12
期刊Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
1860
發行號10
DOIs
出版狀態已發佈 - 十月 1 2017

指紋

Protein Splicing
RNA Stability
Non-Small Cell Lung Carcinoma
Cells
Neoplasm Metastasis
Degradation
Messenger RNA
AU Rich Elements
Proteins
MicroRNAs
RNA-Binding Proteins
Microarray Analysis
Microarrays
Tumors
Neoplasms
Screening
Homeostasis

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Genetics

引用此文

KSRP suppresses cell invasion and metastasis through miR-23a-mediated EGR3 mRNA degradation in non-small cell lung cancer. / Chien, Ming Hsien; Lee, Wei Jiunn; Yang, Yi Chieh; Li, Yin Lin; Chen, Bo Rong; Cheng, Tsu Yao; Yang, Pei Wen; Wang, Ming Yang; Jan, Yi Hua; Lin, Yen Kuang; Lee, Jang Ming; Hsiao, Michael; Chen, Jin Shing; Hua, Kuo Tai.

於: Biochimica et Biophysica Acta - Gene Regulatory Mechanisms, 卷 1860, 編號 10, 01.10.2017, p. 1013-1024.

研究成果: 雜誌貢獻文章

Chien, Ming Hsien ; Lee, Wei Jiunn ; Yang, Yi Chieh ; Li, Yin Lin ; Chen, Bo Rong ; Cheng, Tsu Yao ; Yang, Pei Wen ; Wang, Ming Yang ; Jan, Yi Hua ; Lin, Yen Kuang ; Lee, Jang Ming ; Hsiao, Michael ; Chen, Jin Shing ; Hua, Kuo Tai. / KSRP suppresses cell invasion and metastasis through miR-23a-mediated EGR3 mRNA degradation in non-small cell lung cancer. 於: Biochimica et Biophysica Acta - Gene Regulatory Mechanisms. 2017 ; 卷 1860, 編號 10. 頁 1013-1024.
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abstract = "KH-type splicing regulatory protein (KSRP) is a single-strand RNA binding protein which regulates mRNA stability either by binding to AU-rich elements (AREs) of mRNA 3′UTR or by facilitating miRNA biogenesis to target mRNA. Unlike its well-characterized function at the molecular level in maintaining RNA homeostasis, the role of KSRP in cancer progression remains largely unknown. Here we investigate the role of KSRP in non-small cell lung cancer (NSCLC). We first examined KSRP expression by immunohistochemistry in a cohort containing 196 NSCLC patients and observed a strong positive correlation between KSRP expression and survival of NSCLC patients. Multivariate analysis further identified KSRP as an independent prognostic factor. Manipulating KSRP expression significantly affected in vitro cell mobility and in vivo metastatic ability of NSCLC cells. Microarray analysis identified an ARE-containing gene, EGR3, as a downstream effector of KSRP in NSCLC. Interestingly, we found that KSRP decreased EGR3 mRNA stability in an ARE-independent manner. By screening KSRP-regulated miRNAs in NSCLC cells, we further found that miR-23a directly binds to EGR3 3′UTR, reducing EGR3 expression and thereby inhibiting NSCLC cell mobility. Our findings implicate a targetable KSRP/miR-23a/EGR3 signaling axis in advanced tumor phenotypes.",
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T1 - KSRP suppresses cell invasion and metastasis through miR-23a-mediated EGR3 mRNA degradation in non-small cell lung cancer

AU - Chien, Ming Hsien

AU - Lee, Wei Jiunn

AU - Yang, Yi Chieh

AU - Li, Yin Lin

AU - Chen, Bo Rong

AU - Cheng, Tsu Yao

AU - Yang, Pei Wen

AU - Wang, Ming Yang

AU - Jan, Yi Hua

AU - Lin, Yen Kuang

AU - Lee, Jang Ming

AU - Hsiao, Michael

AU - Chen, Jin Shing

AU - Hua, Kuo Tai

PY - 2017/10/1

Y1 - 2017/10/1

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AB - KH-type splicing regulatory protein (KSRP) is a single-strand RNA binding protein which regulates mRNA stability either by binding to AU-rich elements (AREs) of mRNA 3′UTR or by facilitating miRNA biogenesis to target mRNA. Unlike its well-characterized function at the molecular level in maintaining RNA homeostasis, the role of KSRP in cancer progression remains largely unknown. Here we investigate the role of KSRP in non-small cell lung cancer (NSCLC). We first examined KSRP expression by immunohistochemistry in a cohort containing 196 NSCLC patients and observed a strong positive correlation between KSRP expression and survival of NSCLC patients. Multivariate analysis further identified KSRP as an independent prognostic factor. Manipulating KSRP expression significantly affected in vitro cell mobility and in vivo metastatic ability of NSCLC cells. Microarray analysis identified an ARE-containing gene, EGR3, as a downstream effector of KSRP in NSCLC. Interestingly, we found that KSRP decreased EGR3 mRNA stability in an ARE-independent manner. By screening KSRP-regulated miRNAs in NSCLC cells, we further found that miR-23a directly binds to EGR3 3′UTR, reducing EGR3 expression and thereby inhibiting NSCLC cell mobility. Our findings implicate a targetable KSRP/miR-23a/EGR3 signaling axis in advanced tumor phenotypes.

KW - Cell invasion

KW - KSRP

KW - Metastasis

KW - miRNA processing

KW - mRNA decay

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