Heat shock protein 47 regulated by miR-29a to enhance glioma tumor growth and invasion.

Abstract

Heat shock protein 47 (HSP47), also known as SERPINH1, is a product of CBP2 gene located at chromosome 11q13.5, a region frequently amplified in human cancers. HSP47 has been demonstrated to effect on limiting tumor invasion and motility. The previous studies showed that HSP47 is overexpressed in many human cancers, including stomach cancer, lung cancer, pancreatic ductal adenocarcinoma, and ulcerative colitis-associated carcinomas. However, the role of HSP47 in human glioma is still unknown. Here, we examined the expression of HSP47 in a group of glioma tumors and matched non-tumor brain tissues using qRT-PCR. We found that HSP47 is significantly overexpressed in glioma tissues and cell lines and associated with glioma tumor grade. Next, we knockdown the expression of HSP47 in the glioma cells using small interfering RNAs. The result showed that knockdown of HSP47 inhibits glioma cell growth, migration and invasion in vitro. We further investigated the posttranscriptional regulation of HSP47 by microRNAs using bioinformatics analysis and experimental validation. The results suggested that the expression of HSP47 is regulated by miR-29a. Finally, stable knockdown of HSP47 using shRNA inhibits glioma tumor growth and induces apoptosis in mice models in vivo. Therefore, our data suggested that HSP47 regulated by miR-29a to enhance glioma tumor growth and invasion. Taken together, HSP47 plays important role in tumor growth and invasion and thus could be a therapeutic target for treating glioma in the future.

• Authors: Dan Zhao, Xiaochun Jiang, Chengyun Yao, Li Zhang, Huixiang Liu, Hongping Xia, Yongsheng Wang
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 118 Issue 1 Pg. 39-47 (May 2014) ISSN: 1573-7373 [Electronic] United States
• PMID: 24595468 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HSP47 Heat-Shock Proteins
• MIRN29a microRNA, human
• MicroRNAs
• RNA, Small Interfering
• SERPINH1 protein, human

Topics

• Animals
• Brain Neoplasms (metabolism)
• Cell Line, Transformed
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Disease Models, Animal
• Gene Expression Regulation, Neoplastic (genetics)
• Glioma (metabolism, pathology)
• HSP47 Heat-Shock Proteins (genetics, metabolism)
• Humans
• In Situ Nick-End Labeling
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Neoplasm Invasiveness (physiopathology)
• RNA, Small Interfering (genetics, metabolism)
• Time Factors
• Transfection