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Let-7f通过靶向骨膜蛋白抑制胶质瘤细胞的增殖、迁移和侵袭。

Let-7f Inhibits Glioma Cell Proliferation, Migration, and Invasion by Targeting Periostin.

作者信息

Yan Shaofeng, Han Xiao, Xue Hao, Zhang Ping, Guo Xing, Li Tong, Guo Xiaofan, Yuan Guang, Deng Lin, Li Gang

机构信息

Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R., China.

Department of Neurosurgery, Zibo Zhong Xin Hospital, Zibo, Shandong Province, P.R., China.

出版信息

J Cell Biochem. 2015 Aug;116(8):1680-92. doi: 10.1002/jcb.25128.

DOI:10.1002/jcb.25128
PMID:25735962
Abstract

Glioma is one of the most aggressive and malignant tumor types. Despite advances in surgery, imaging, chemotherapy, and radiation, glioma patient prognosis remains poor. Glioma pathogenesis is an urgent problem that must be solved. MicroRNAs (miRNAs) are endogenous small non-coding RNAs that are key post-transcriptional regulators of gene expression. miRNA deregulation commonly occurs in human tumorigenesis. In the present study, the expression levels of Let-7f were down-regulated in both glioma tissues and glioma cells. The enhanced expression of Let-7f suppressed glioma cells proliferation, migration, and invasion via direct targeting perisotin oncogenic activity. Experiments with periostin siRNA or over-expression further suggest that Let-7f may serve as tumor suppressors through perisotin signal. These findings provide insights regarding the role and mechanism of Let-7f in regulating biological behavior of glioma cells via the Let-7f/periostin axis, and Let-7f may serve as a potential therapeutic target in glioma.

摘要

胶质瘤是最具侵袭性和恶性的肿瘤类型之一。尽管在手术、影像学、化疗和放疗方面取得了进展,但胶质瘤患者的预后仍然很差。胶质瘤的发病机制是一个亟待解决的问题。微小RNA(miRNA)是内源性小非编码RNA,是基因表达的关键转录后调节因子。miRNA失调在人类肿瘤发生中普遍存在。在本研究中,Let-7f在胶质瘤组织和胶质瘤细胞中的表达水平均下调。Let-7f的表达增强通过直接靶向骨膜素致癌活性抑制了胶质瘤细胞的增殖、迁移和侵袭。骨膜素siRNA或过表达实验进一步表明,Let-7f可能通过骨膜素信号作为肿瘤抑制因子。这些发现为Let-7f通过Let-7f/骨膜素轴调节胶质瘤细胞生物学行为的作用和机制提供了见解,并且Let-7f可能作为胶质瘤的潜在治疗靶点。

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