High-mobility group box 2 (HMGB2) modulates radioresponse and is downregulated by p53 in colorectal cancer cell

Shin, Young-Joo; Kim, Misook; Kim, Moon-Sun; Lee, Joon Seok; Kang, Miae; Jeong, Jong Ju

doi:10.4161/cbt.23292

Cited by 28 publications

(29 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, HMGB1 has been shown to be a promising therapeutic target for prostate cancer (25). siRNA-mediated depletion of HMGB2 has been shown to increase chemo-and radiosensitivity of head and neck squamous cell carcinomas (26), breast cancer cells (27), and colorectal cancer cells (28). Similarly, HMGB3 depletion has been shown to lower the proliferative potential of colorectal cancer cells (29).…”

Section: Discussionmentioning

confidence: 99%

Targeting the High-Mobility Group Box 3 Protein Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin

et al. 2019

View full text Add to dashboard Cite

Chemotherapeutic regimens for ovarian cancer often include the use of DNA interstrand crosslink-inducing agents (e.g., platinum drugs) or DNA double-strand break-inducing agents. Unfortunately, the majority of patients fail to maintain a durable response to treatment, in part, due to drug resistance, contributing to a poor survival rate. In this study, we report that cisplatin sensitivity can be restored in cisplatin-resistant ovarian cancer cells by targeting the chromatin-associated high-mobility group box 3 (HMGB3) protein. HMGB proteins have been implicated in the pathogenesis and prognosis of ovarian cancer, and HMGB3 is often upregulated in cancer cells, making it a potential selective target for therapeutic intervention. Depletion of HMGB3 in cisplatin-sensitive and cisplatin-resistant cells resulted in transcriptional downregu-lation of the kinases ATR and CHK1, which attenuated the ATR/CHK1/p-CHK1 DNA damage signaling pathway. HMGB3 was associated with the promoter regions of ATR and CHK1, suggesting a new role for HMGB3 in transcriptional regulation. Furthermore, HMGB3 depletion significantly increased apoptosis in cisplatin-resistant A2780/CP70 cells after cisplatin treatment. Taken together, our results indicate that targeted depletion of HMGB3 attenuates cisplatin resistance in human ovarian cancer cells, increasing tumor cell sensitivity to platinum drugs.Significance: This study shows that targeting HMGB3 is a potential therapeutic strategy to overcome chemoresistance in ovarian cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Targeting the High-Mobility Group Box 3 Protein Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Lack of epigenetic stemness features in HESCs was further associated with intragenic hypomethylation and reduced expression of HMGB2 , coding one of four members of the HMGB family. HMGB2 is a multifaceted protein involved in chromatin bending and DNA damage repair . It also functions as a major progesterone receptor coactivator .…”

Section: Discussionmentioning

confidence: 99%

Loss of Endometrial Plasticity in Recurrent Pregnancy Loss

et al. 2015

View full text Add to dashboard Cite

Menstruation drives cyclic activation of endometrial progenitor cells, tissue regeneration, and maturation of stromal cells, which differentiate into specialized decidual cells prior to and during pregnancy. Aberrant responsiveness of human endometrial stromal cells (HESCs) to deciduogenic cues is strongly associated with recurrent pregnancy loss (RPL), suggesting a defect in cellular maturation. MeDIP-seq analysis of HESCs did not reveal gross perturbations in CpG methylation in RPL cultures, although quantitative differences were observed in or near genes that are frequently deregulated in vivo. However, RPL was associated with a marked reduction in methylation of defined CA-rich motifs located throughout the genome but enriched near telomeres. Non-CpG methylation is a hallmark of cellular multipotency. Congruently, we demonstrate that RPL is associated with a deficiency in endometrial clonogenic cell populations. Loss of epigenetic stemness features also correlated with intragenic CpG hypomethylation and reduced expression of HMGB2, coding high mobility group protein 2. We show that knockdown of this sequence-independent chromatin protein in HESCs promotes senescence and impairs decidualization, exemplified by blunted time-dependent secretome changes. Our findings indicate that stem cell deficiency and accelerated stromal senescence limit the differentiation capacity of the endometrium and predispose for pregnancy failure. STEM CELLS 2016;34:346-356 SIGNIFICANCE STATEMENTRecurrent pregnancy loss (RPL) is a common and distressing disorder. While many risk factors have been invoked to explain RPL, the underlying pathological pathways are not understood. We demonstrate that RPL is strongly associated with uterine stem cell deficiency and enhanced cellular senescence. This in turn perturbs endometrial preparation for pregnancy, a process termed decidualization, and persistence of these defects over several conception cycles will lead to consecutive miscarriages. Our findings open up new avenues to screen women prior to pregnancy for the risk of miscarriage and point to the potential of cell-based therapies in the prevention of RPL.

show abstract

“…In glioblastoma, HMGB2 overexpression conferred resistance to temozolomide treatment and siRNA‐mediated silencing of HMGB2 improved sensitivity to the drug . Silencing of HMGB2 has been associated with increased sensitivity to ionizing radiation in colorectal cancer cells In hepatocellular carcinoma, overexpression of HMGB2 has been associated with decrease in cisplatin‐ and etoposide‐induced cell death, aggressive tumor growth, and poor prognosis .…”

Section: Resultsmentioning

confidence: 99%

“…Silencing of HMGB2 has been associated with increased sensitivity to ionizing radiation in colorectal cancer cells [65] In hepatocellular carcinoma, overexpression of HMGB2 has been associated with decrease in cisplatin-and etoposideinduced cell death, aggressive tumor growth, and poor prognosis [8].…”

Section: Sirna-mediated Silencing Of Hmgb2 Enhances Sensitivity To CImentioning

confidence: 99%

Silencing of high‐mobility group box 2 (HMGB2) modulates cisplatin and 5‐fluorouracil sensitivity in head and neck squamous cell carcinoma

et al. 2015

View full text Add to dashboard Cite

Dysregulation of protein expression is associated with most diseases including cancer. Mass spectrometry-based proteomic analysis is widely employed as a tool to study protein dysregulation in cancers. Proteins which are differentially expressed in head and neck squamous cell carcinoma (HNSCC) cell lines compared to the normal oral cell line could serve as biomarkers for patient stratification. To understand the proteomic complexity in HNSCC, we carried out iTRAQ-based mass spectrometry analysis on a panel of HNSCC cell lines in addition to a normal oral keratinocyte cell line. LC-MS/MS analysis of total proteome of the HNSCC cell lines led to the identification of 3,263 proteins, of which 185 proteins were overexpressed and 190 proteins were downregulated more than 2-fold in at least two of the three HNSCC cell lines studied. Amongst the overexpressed proteins, 23 proteins were related to DNA replication and repair. These included high mobility group box 2 (HMGB2) protein, which was overexpressed in all three HNSCC lines studied. Overexpression of HMGB2 has been reported in various cancers, yet its role in HNSCC remains unclear. Immunohistochemical labeling of HMGB2 in a panel of HNSCC tumors using tissue microarrays revealed overexpression in 77% (54 of 70) of tumors. The HMGB proteins are known to bind to DNA structure resulting from cisplatin-DNA adducts and affect the chemosensitivity of cells. We observed that siRNA-mediated silencing of HMGB2 increased the sensitivity of the HNSCC cell lines to cisplatin and 5-FU. We hypothesize that targeting HMGB2 could enhance the efficacy of existing chemotherapeutic regimens for treatment of HNSCC.

show abstract

High-mobility group box 2 (HMGB2) modulates radioresponse and is downregulated by p53 in colorectal cancer cell

Cited by 28 publications

References 37 publications

Targeting the High-Mobility Group Box 3 Protein Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin

Targeting the High-Mobility Group Box 3 Protein Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin

Loss of Endometrial Plasticity in Recurrent Pregnancy Loss

Silencing of high‐mobility group box 2 (HMGB2) modulates cisplatin and 5‐fluorouracil sensitivity in head and neck squamous cell carcinoma

Contact Info

Product

Resources

About