HMGB1 knockdown increases MM cell vulnerability by regulating autophagy and DNA damage repair

Journal of Experimental & Clinical Cancer Research : CR
Xing GuoZhen Cai

Abstract

With the development of novel therapeutic agents, the survival of multiple myeloma (MM) patients has much improved. However, the disease is incurable due to drug resistance. Previous studies have found that high-mobility group box 1 (HMGB1) is involved in inflammation, angiogenesis, DNA damage repair, and cancer invasion, progression, metastasis and drug resistance and that high HMGB1 expression is associated with poor MM prognosis, yet the role and mechanism of HMGB1 in MM remains unclear. Through gene expression and Oncomine database analyses, we found that HMGB1 is associated with a poor prognosis in MM patients. RNA interference together with gene array analysis, cell proliferation and apoptosis assays, autophagy detection assays, western blotting, and in vivo xenograft models were employed to evaluate the effect of HMGB1 and the mechanism involved in MM drug resistance. MM cell lines and primary MM samples were found to express high levels of HMGB1, which was negatively associated with the 3-year survival of MM patients. HMGB1 knockdown in MM cells enhanced the inhibitory effect of chemotherapy with dexamethasone (Dex) via apoptosis induction. Furthermore, downregulation of HMGB1 activated the mTOR pathway, inhibited autop...Continue Reading

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Citations

Feb 2, 2019·Cells·Mojgan Djavaheri-MergnyMagali Humbert
Oct 31, 2019·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Ying ShiJingjing Ren
Jul 15, 2020·Journal of Hematology & Oncology·Shunling YuanJi Zhang
Aug 28, 2021·International Journal of Molecular Sciences·Giuseppe MurdacaSebastiano Gangemi

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Methods Mentioned

BETA
electrophoresis
flow cytometry
xenografts
transfection

Software Mentioned

GEP
ModFit
GraphPad
FlowJo
GraphPad Prism

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