HMGB1 knockdown effectively inhibits the progression of rectal cancer by suppressing HMGB1 expression and promoting apoptosis of rectal cancer cells

Wang, Zhiwei; Wang, Xiaoyan; Li, Jiantian; Yang, Cheng; Xing, Zhiyuan; Chen, Ruiyun; Xu, Fei

doi:10.3892/mmr.2016.5340

Cited by 12 publications

(9 citation statements)

References 28 publications

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“…Previous studies have demonstrated that downregulating HMGB1 in cancer cells such as gastric cancer [ 19 ], bladder cancer [ 20 ], and non-small cell lung cancer [ 21 ] through RNA interference (RNAi) or micro-RNA overexpression can inhibit cell proliferation and induce cell cycle arrest or apoptosis to increase the sensitivity of tumor cells to chemotherapy [ 5 ]. Another study in rectal cancer [ 22 ] found that HMGB1 knockdown by RNAi activated caspase-3 and PARP, downregulated Bcl-2 expression and eventually induced apoptosis in rectal cancer cells. In the present study, the expression levels of anti-apoptotic proteins Bcl-2 and Bcl-xl were downregulated after HMGB1 knockdown, indicating that suppressing HMGB1 expression can induce MM apoptosis by regulating Bcl-2 and Bcl-xl expression.…”

Section: Discussionmentioning

confidence: 99%

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

Guo

Zhang

et al. 2018

J Exp Clin Cancer Res

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BackgroundWith 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.MethodsThrough 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.ResultsMM 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 autophagy and increased DNA damage induced by Dex by modulating expression of related genes. In vivo, xenograft models showed that after Dex treatment, the tumor burden of HMGB1-knockdown mice was decreased compared with that of control mice.ConclusionsOur research shows that HMGB1 participates in autophagy and DNA damage repair and that downregulation of HMGB1 enhances the sensitivity of MM cells to Dex, suggesting that HMGB1 may serve as a target for MM treatment.

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Section: Discussionmentioning

confidence: 99%

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

Guo

Zhang

et al. 2018

J Exp Clin Cancer Res

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“…135 It is reported that HMGB1 may play a significant role in apoptosis by suppressing pro-apoptotic proteins such as caspase-3 and BAX or promoting anti-proapoptotic proteins including Bcl-2. 136 Bcl-2 is responsible for the suppression of the efflux of cytochrome and the pro-apoptotic proteins. Its activity can also be inhibited by ABT-737, which is a negative target of HMGB1.…”

Section: Xiao and Liu 73mentioning

confidence: 99%

Biological functions and theranostic potential of HMGB family members in human cancers

et al. 2020

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The high mobility group box (HMGB) protein family consists of four members: HMGB1, 2, 3, and 4. They share similar amino acid sequences and identical functional regions, especially HMGB1, 2, and 3. The homology in structure may lead to similarity in function. In fact, though their targets may be different, they all possess the fundamental function of binding and distorting target DNAs. However, further research confirmed they are distributed differently in tissues and involved in various distinct physiological and pathological cellular processes, including cell proliferation, division, migration, and differentiation. Recently, the roles of HMGB family members in carcinogenesis has been widely investigated; however, systematic discussion on their functions and clinical values in malignant tumors is limited. In this review, we mainly review and summarize recent advances in knowledge of HMGB family members in terms of structure, distribution, biochemical cascades, and specific mechanisms regarding tumor progression. Importantly, the diagnostic, prognostic, and therapeutic value of these proteins in cancers is discussed. Finally, we envisage the orientation and challenges of this field in further studies.

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“…Previous studies have reported that high-mobility group box 1 protein (HMGB1) was a critical factor in the development of chemoresistance (14)(15)(16), and notably, that it promoted drug resistance in osteosarcoma, thus suggesting a novel target for improving osteosarcoma therapy (15,(17)(18)(19). Recently, Meng et al (20) observed that the tumorigenesis, invasion and metastasis of osteosarcoma was associated with overexpression of HMGB1, which may thus be a potential target for treatment (20).…”

Section: Introductionmentioning

confidence: 99%

Necrosis of osteosarcoma cells induces the production and release of high‑mobility group box 1 protein

Yang

Wang

et al. 2017

Exp Ther Med

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Abstract. Osteosarcoma is among the commonly observed malignancies worldwide. High-mobility group box 1 protein (HMGB1) is a highly conserved protein and is involved in the progression of various types of human cancer. The aim of the present study was to explore whether the level of HMGB1 was involved in the necrosis of osteosarcoma cells. Doxorubicin (DXR), as an inducer of necrosis, was administered to human osteosarcoma cell lines (MG63, Saos-2 and U2OS), and the results indicated that 0.5 µg/ml DXR significantly induced the necrosis of MG63 cells (P<0.01), while 0.5 and 1.0 µg/ml DXR suppressed the viability of MG63 and U2OS cells (P<0.05), relative to untreated controls. Additionally, treatment with DXR was observed by western blot analysis to markedly increase the expression levels of HMGB1 in MG63 cells, and to significantly increase the levels of secreted HMGB1 in the supernatants of MG63 and U2OS cells (P<0.01). In conclusion, cell necrosis increased the level of HMGB1 in osteosarcoma cells, as well as the level of secreted HMGB1 in cell supernatants. Therefore, HMGB1 may be a potential target in molecular therapy for patients with osteosarcoma.

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HMGB1 knockdown effectively inhibits the progression of rectal cancer by suppressing HMGB1 expression and promoting apoptosis of rectal cancer cells

Cited by 12 publications

References 28 publications

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

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

Biological functions and theranostic potential of HMGB family members in human cancers

Necrosis of osteosarcoma cells induces the production and release of high‑mobility group box 1 protein

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