Osteopontin Splice Variants Differentially Exert Clinicopathological Features and Biological Functions in Gastric Cancer

<p><b>Purpose: </b> Gastric cancer (GC) remains a leading cause of death worldwide, and an elevated expression of osteopontin (OPN) may correlate with its poor survival. Alternative splicing of OPN can result in three isoforms, OPN-a, OPN-b and OPN-c. The aim of our current study i...

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Main Author: Xiaojian Tang, Jianfang Li, Beiqin Yu, Liping Su, Yingyan Yu, Min Yan, Bingya Liu, Zhenggang Zhu
Format: Article
Language:English
Published: Ivyspring International Publisher 2013-01-01
Series:International Journal of Biological Sciences
Online Access:http://www.biolsci.org/v09p0055.htm
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spelling doaj-19046230e1e1460f9a93c0e40dc96d2c2020-11-24T22:47:19ZengIvyspring International PublisherInternational Journal of Biological Sciences1449-22882013-01-01915566Osteopontin Splice Variants Differentially Exert Clinicopathological Features and Biological Functions in Gastric CancerXiaojian Tang, Jianfang Li, Beiqin Yu, Liping Su, Yingyan Yu, Min Yan, Bingya Liu, Zhenggang Zhu<p><b>Purpose: </b> Gastric cancer (GC) remains a leading cause of death worldwide, and an elevated expression of osteopontin (OPN) may correlate with its poor survival. Alternative splicing of OPN can result in three isoforms, OPN-a, OPN-b and OPN-c. The aim of our current study is to examine the expression pattern and biological functions of OPN splice variants in GC.</p><p><b>Methods:</b> Firstly, we evaluated the expression of OPN splice variants in 7 gastric cell lines, 101 pairs of GC tissues and their adjacent non-tumor tissues by Quantative real-time PCR (QT-PCR). Gain-of-function experiments were subsequently performed to determine their diverse roles in malignant behaviors of GC. Besides, their differential effects on the regulation of crucial downstream molecules were further explored in the anti-apoptotic and pro-metastatic process.</p><p><b>Results:</b> We found that OPN-b is the dominant kind of OPN isoform in GC cell lines. Although the expression levels of three variants were all elevated in GC tissues, increased OPN-b or OPN-c expression could correlate with clinicopathological features. Functional analyses further showed that OPN-b most strongly promoted GC cell survival possibly by regulation of Bcl-2 family proteins and CD44v expressions. Moreover, OPN-c most effectively stimulated GC metastatic activity by increasing secretion of MMP-2, uPa, and IL-8.</p><p><b>Conclusions:</b> Our results suggest that OPN splice variants differentially exert clinicopathological features and biological functions in GC. Therefore, focusing on specific OPN isoform could be a novel direction for developing diagnostic and therapeutic approaches in GC.</p>http://www.biolsci.org/v09p0055.htm
collection DOAJ
language English
format Article
sources DOAJ
author Xiaojian Tang, Jianfang Li, Beiqin Yu, Liping Su, Yingyan Yu, Min Yan, Bingya Liu, Zhenggang Zhu
spellingShingle Xiaojian Tang, Jianfang Li, Beiqin Yu, Liping Su, Yingyan Yu, Min Yan, Bingya Liu, Zhenggang Zhu
Osteopontin Splice Variants Differentially Exert Clinicopathological Features and Biological Functions in Gastric Cancer
International Journal of Biological Sciences
author_facet Xiaojian Tang, Jianfang Li, Beiqin Yu, Liping Su, Yingyan Yu, Min Yan, Bingya Liu, Zhenggang Zhu
author_sort Xiaojian Tang, Jianfang Li, Beiqin Yu, Liping Su, Yingyan Yu, Min Yan, Bingya Liu, Zhenggang Zhu
title Osteopontin Splice Variants Differentially Exert Clinicopathological Features and Biological Functions in Gastric Cancer
title_short Osteopontin Splice Variants Differentially Exert Clinicopathological Features and Biological Functions in Gastric Cancer
title_full Osteopontin Splice Variants Differentially Exert Clinicopathological Features and Biological Functions in Gastric Cancer
title_fullStr Osteopontin Splice Variants Differentially Exert Clinicopathological Features and Biological Functions in Gastric Cancer
title_full_unstemmed Osteopontin Splice Variants Differentially Exert Clinicopathological Features and Biological Functions in Gastric Cancer
title_sort osteopontin splice variants differentially exert clinicopathological features and biological functions in gastric cancer
publisher Ivyspring International Publisher
series International Journal of Biological Sciences
issn 1449-2288
publishDate 2013-01-01
description <p><b>Purpose: </b> Gastric cancer (GC) remains a leading cause of death worldwide, and an elevated expression of osteopontin (OPN) may correlate with its poor survival. Alternative splicing of OPN can result in three isoforms, OPN-a, OPN-b and OPN-c. The aim of our current study is to examine the expression pattern and biological functions of OPN splice variants in GC.</p><p><b>Methods:</b> Firstly, we evaluated the expression of OPN splice variants in 7 gastric cell lines, 101 pairs of GC tissues and their adjacent non-tumor tissues by Quantative real-time PCR (QT-PCR). Gain-of-function experiments were subsequently performed to determine their diverse roles in malignant behaviors of GC. Besides, their differential effects on the regulation of crucial downstream molecules were further explored in the anti-apoptotic and pro-metastatic process.</p><p><b>Results:</b> We found that OPN-b is the dominant kind of OPN isoform in GC cell lines. Although the expression levels of three variants were all elevated in GC tissues, increased OPN-b or OPN-c expression could correlate with clinicopathological features. Functional analyses further showed that OPN-b most strongly promoted GC cell survival possibly by regulation of Bcl-2 family proteins and CD44v expressions. Moreover, OPN-c most effectively stimulated GC metastatic activity by increasing secretion of MMP-2, uPa, and IL-8.</p><p><b>Conclusions:</b> Our results suggest that OPN splice variants differentially exert clinicopathological features and biological functions in GC. Therefore, focusing on specific OPN isoform could be a novel direction for developing diagnostic and therapeutic approaches in GC.</p>
url http://www.biolsci.org/v09p0055.htm
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