HMGB3 promotes the proliferation and metastasis of glioblastoma and is negatively regulated by miR-200b-3p and miR-200c-3p

作者：Liu, Jianxun; Wang, Liling; Li, Xuesong^*

来源：Cell Biochemistry and Function, 2018, 36(7): 357-365.

DOI：10.1002/cbf.3355

• glioblastoma
• HMGB3
• metastasis
• miR-200b-3p
• miR-200c-3p
• proliferation

High mobility group box 3 (HMGB3) is strongly involved in oncogenesis in a variety of cancers. In the present study, we have explored the role of HMGB3 in glioblastoma multiforme (GBM) tumorigenesis and have identified the microRNAs (miRNAs) miR-200b-3p and miR-200c-3p as negative regulators of HMGB3 expression. We began by determining that endogenous HMGB3 expression levels were significantly elevated in GBM tissues and in 3 GBM cell lines. To study the function of HMGB3 in GBM, we transfected a small-interfering RNA (siRNA) against HMGB3 into GBM cell lines U251 and LN229. MTT and tumour sphere assays demonstrated that HMGB3 knockdown significantly inhibited cell proliferation. Wound healing and transwell assays determined that HMGB3 knockdown substantially suppressed GBM cell migration and invasion. We evaluated the effects of HMGB3 knockdown on MAPK phosphorylation and target gene expression, finding that HMGB3 knockdown significantly reduced MAPK phosphorylation (p-ERK (1/2), p-p38, and p-JNK). We then used the biologic prediction algorithm TargetScan to identify the 3 untranslated region (3-UTR) of HMGB3 as a target of miR-200b-3p and miR-200c-3p. Luciferase, qRT-PCR, and western blot assays confirmed that miR-200b-3p and miR-200c-3p bind and inhibit HMGB3 expression. Finally, Pearson correlation analyses demonstrated a negative correlation between relative HMGB3 mRNA and miR-200b/c-3p expression levels in GBM tissue samples. Overall, the present study strongly suggests that HMGB3 promotes GBM oncogenesis through the MAPK signalling pathway while miR-200b-3p and miR-200c-3p inhibit its expression.

• 出版日期2018-10
• 单位大庆油田总医院