HMGN5 blockade by siRNA enhances apoptosis, suppresses invasion and increases chemosensitivity to temozolomide in meningiomas.

Abstract

The high-mobility group nucleosome-binding protein-5 (HMGN5) is frequently overexpressed in various malignant cancers. However, the potential correlation between HMGN5 and prognosis in patients with meningiomas remains unknown. In the present study, we explored the expression of HMGN5 in meningiomas with immunohistochemistry and correlated the results to the patient outcome. Potential effects of HMGN5 on tumor growth, apoptosis and invasion were also examined in representative cell lines (IOMM-Lee and CH157) by downregulating HMGN5 with RNA interference (siRNA). We demonstrate that there is a positive association between HMGN5 expression and meningioma histological grade. Statistical analysis reveals that lower HMGN5 expression predict lower meningioma recurrence. In addition, downregulation of HMGN5 inhibits IOMM-Lee and CH157 cell proliferation, enhances cell apoptosis and suppresses tumor invasion. Our results further revealed that HMGN5 inhibition decreased P-glycoprotein (MDR-1) expression without affecting multidrug resistance associated proteins 1 (MRP-1) expression to increase chemosensitivity to temozolomide (TMZ) of meningioma cells. Collectively, this study indicates that HMGN5 is a novel target for developing effective therapeutic strategies for malignant meningiomas.

• Authors: Jing He, Chaoyang Liu, Bin Wang, Na Li, Guoqin Zuo, Dewei Gao
• Journal: International journal of oncology (Int J Oncol) Vol. 47 Issue 4 Pg. 1503-11 (Oct 2015) ISSN: 1791-2423 [Electronic] Greece
• PMID: 26315299 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• HMGN Proteins
• HMGN5 protein, human
• RNA, Small Interfering
• Trans-Activators
• Dacarbazine
• Temozolomide

Topics

• Aged
• Antineoplastic Agents (pharmacology)
• Apoptosis (physiology)
• Blotting, Western
• Dacarbazine (analogs & derivatives, pharmacology)
• Drug Resistance, Neoplasm (genetics)
• Female
• Gene Knockdown Techniques
• HMGN Proteins (genetics, metabolism)
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Male
• Meningeal Neoplasms (mortality, pathology)
• Meningioma (mortality, pathology)
• Middle Aged
• Neoplasm Invasiveness (genetics)
• Prognosis
• RNA, Small Interfering
• Reverse Transcriptase Polymerase Chain Reaction
• Temozolomide
• Trans-Activators (genetics, metabolism)
• Transfection