Osteopontin splice variants differentially exert clinicopathological features and biological functions in gastric cancer.
Osteopontin splice variants differentially exert clinicopathological features and biological functions in gastric cancer.
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骨桥蛋白剪接变异体在胃癌中发挥不同的临床病理特征和生物学功能
DOI：
10.7150/ijbs.5280
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发表时间：
2013
影响因子：
9.2
通讯作者：
Zhu Z
中科院分区：
文献类型：
--
作者：
Tang X;Li J;Yu B;Su L;Yu Y;Yan M;Liu B;Zhu Z
目的：胃癌（GC）是世界范围内的主要死亡原因，骨桥蛋白（OPN）的高表达可能与其不良生存相关。OPN的选择性剪接可以产生三种亚型，OPN-a，OPN-b和OPN-c。本研究的目的是探讨骨桥蛋白剪接变异体在胃癌中的表达模式和生物学功能。研究方法：首先，我们采用定量实时荧光定量PCR（QT-PCR）检测了7种胃癌细胞系、101对胃癌组织及其癌旁组织中OPN剪接变异体的表达。随后进行功能获得实验以确定它们在GC恶性行为中的不同作用。此外，在抗凋亡和促转移过程中，它们对关键下游分子的调节的差异作用被进一步探索。结果：OPN-b是胃癌细胞中的优势亚型。虽然三种变体在胃癌组织中的表达水平均升高，但OPN-b或OPN-c的表达升高可能与临床病理特征相关。功能分析进一步表明OPN-b可能通过调节Bcl-2家族蛋白和CD 44 v表达而最强烈地促进GC细胞存活。此外，OPN-c通过增加MMP-2、uPa和IL-8的分泌最有效地刺激GC转移活性。结论：我们的研究结果表明，OPN剪接变异体在GC中发挥不同的临床病理特征和生物学功能。因此，关注特定的OPN亚型可能是开发GC诊断和治疗方法的新方向。
Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.
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DOI：
10.1186/1748-717x-4-58
发表时间：
2009-11-26
期刊：
Radiation oncology (London, England)
影响因子：
--
作者：
Bordón E;Henríquez Hernández LA;Lara PC;Pinar B;Fontes F;Rodríguez Gallego C;Lloret M
通讯作者：
Lloret M
影响因子：
4.1
作者：
HIJIYA, N;SETOGUCHI, M;YAMAMOTO, S
通讯作者：
YAMAMOTO, S
影响因子：
4.8
作者：
Philip, S;Kundu, GC
通讯作者：
Kundu, GC
影响因子：
8.3
作者：
Chen W;Ma Q;Suzuki H;Hartman R;Tang J;Zhang JH
通讯作者：
Zhang JH
影响因子：
5.5
作者：
Junaid, Asad;Moon, Michael C.;Zahradka, Peter
通讯作者：
Zahradka, Peter