Upregulation of miR-513b inhibits cell proliferation, migration, and promotes apoptosis by targeting high mobility group-box 3 protein in gastric cancer.

Abstract

The high mobility group-box 3 (HMGB3) protein belongs to the high mobility group box (HMG-box) subfamily, and recent studies have shown that HMGB3 is an oncogene for leukemia. HMGB3 is also expressed at a high level in the progression phase of breast and gastric cancer (GC). Using bioinformatic analyses, we found that HMGB3 is a potential target for miR-513b. However, the pathophysiological role of miR-513b and its relevance to the growth and development of GC have yet to be investigated. This study focuses on whether miR-513b acts as a tumor suppressor in GC. Compared with non-malignant adjacent tissues samples, qRT-PCR data showed significant downregulation of miR-513b in 74 GC tissue samples (P < 0.01). Furthermore, western blotting revealed that HMGB3 protein was overexpressed in tumor samples relative to matched, non-malignant adjacent tissues. Western blotting and qRT-PCR results showed that high expression of HMGB3 and low expression of miR-513b were both significantly associated with primary tumors, lymph node metastases, and the clinical stage (P < 0.01). MiR-513b was shown to not only inhibit the proliferation and migration of gastric cancer cells (MKN45 and SGC7901) in the CCK-8 and transwell assays, but also to promote cell apoptosis in a flow-cytometric apoptosis assay. In western blot and luciferase assays, HMGB3 was identified as a major target of miR-513b. Moreover, we also found that the expression of HMGB3 lacking in 3' UTR could abrogate the anti-migration and pro-apoptosis function of miR-513b. These findings suggest the importance of miR-513b targeting of HMGB3 in the regulation of growth, migration and apoptosis of GC, improve our understanding of the mechanisms of GC pathogenesis, and may promote the development of novel targeted therapies.

• Authors: Xudong Chen, Guoqiang Zhao, Fuqing Wang, Fenglan Gao, Hailan Luo, Yuanyuan Wang, Yuwen Du, Xiaonan Chen, Changgui Xue, Ziming Dong, Guohua Song
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 35 Issue 11 Pg. 11081-9 (Nov 2014) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 25095979 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HMGB3 Protein
• MIRN513A1 microRNA, human
• MicroRNAs
• RNA, Messenger

Topics

• Apoptosis
• Blotting, Western
• Cell Movement
• Cell Proliferation
• Female
• Flow Cytometry
• HMGB3 Protein (genetics, metabolism)
• Humans
• Lymphatic Metastasis
• Male
• MicroRNAs (genetics)
• Middle Aged
• Neoplasm Staging
• Prognosis
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Stomach Neoplasms (genetics, metabolism, pathology)
• Tumor Cells, Cultured