Induction of Thioredoxin-Interacting Protein by a Histone Deacetylase Inhibitor, Entinostat, Is Associated with DNA Damage and Apoptosis in Esophageal Adenocarcinoma

Feingold, Paul L.; Surman, Deborah R.; Brown, Kate; Xu, Yuan; McDuffie, Lucas A.; Shukla, Vivek; Reardon, Emily S.; Crooks, Daniel R.; Trepel, Jane B.; Lee, Sunmin; Gao, Shaojian; Xi, Sichuan; McLoughlin, Kaitlin C.; Diggs, Laurence P.; Beer, David G.; Nancarrow, Derek J.; Neckers, Leonard Μ.; Davis, Jeremy L.; Hoang, Chuong D.; Hernandez, Jonathan M.; Schrump, David S.; Ripley, R. Taylor

doi:10.1158/1535-7163.mct-17-1240

Cited by 22 publications

(13 citation statements)

References 42 publications

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“…TXNIP is expressed at a lower level in various cancers (such as liver, breast and bladder cancer) and is a multifunctional protein that controls various cellular processes, such as cell proliferation, apoptotic signaling, oxidative stress and inflammation [44][45][46][47]. Consistent with the findings that overexpression of TXNIP promotes DNA damage in esophageal adenocarcinoma [48], senescence in vascular endothelial cells [49], we demonstrated that TXNIP, may function downstream of PRMT5 to regulate DNA damage signaling and p21-mediated cellular senescence in U2 OS cells. Surprisingly, similar to that of p21 regulation, we also found that knockdown of PRMT5 only upregulated the protein but not the mRNA level of TXNIP.…”

Section: Discussionsupporting

confidence: 72%

PRMT5-TRIM21 interaction regulates the senescence of osteosarcoma cells by targeting the TXNIP/p21 axis

Tong

et al. 2020

Aging

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Osteosarcoma (OS) is the most common bone malignancy in adolescents and has poor clinical outcomes. Protein arginine methyltransferase 5 (PRMT5) has recently been shown to be aberrantly expressed in various cancers, yet its role in OS remains elusive. Here, we found that PRMT5 was overexpressed in OS and its overexpression predicted poor clinical outcomes. PRMT5 knockdown significantly triggered pronounced senescence in OS cells, as evidenced by the increase in senescence-associated β-galactosidase (SA-β-gal)-stained cells, induction of p21 expression, and upregulation of senescence-associated secretory phenotype (SASP) gene expression. In addition, we found that PRMT5 plays a key role in regulating DNA damaging agents-induced OS cell senescence, possibly, via affecting the repair of DNA damage. Furthermore, we found that TXNIP acts as a key factor mediating PRMT5 depletion-induced DNA damage and cellular senescence. Mechanistically, TRIM21, which interacts with PRMT5, was essential for the regulation of TXNIP/p21 expression. In summary, we propose a model in which PRMT5, by interaction with TRIM21, plays a key role in regulating the TXNIP/p21 axis during senescence in OS cells. The present findings suggest that PRMT5 overexpression in OS cells might confer resistance to chemotherapy and that targeting the PRMT5/TRIM21/TXNIP signaling may enhance the therapeutic efficacy in OS.

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Section: Discussionsupporting

confidence: 72%

PRMT5-TRIM21 interaction regulates the senescence of osteosarcoma cells by targeting the TXNIP/p21 axis

Tong

et al. 2020

Aging

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“…Elevated levels of Trx system proteins (Trx-1, TrxR-1, Trx-2, and TrxR-2) and decreased levels of TNXIP protein are involved in various cancers [ 137 – 140 ]. A similar phenomenon was discovered in oral cancers [ 141 – 143 ] and esophageal adenocarcinoma [ 144 ]. Moreover, Kaplan-Meier's analysis revealed that the expression level of Trx was significantly related with a lower 5-year survival rate in patients with tongue squamous cell carcinoma [ 141 ].…”

Section: Modulate Ros Generation and Elimination To Improve The Efsupporting

confidence: 76%

ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer

Huang

Pan

2020

Oxidative Medicine and Cellular Longevity

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Head and neck cancer is a highly genetic and metabolic heterogeneous collection of malignancies of the lip, oral cavity, salivary glands, pharynx, esophagus, paranasal sinuses, and larynx with five-year survival rates ranging from 12% to 93%. Patients with head and neck cancer typically present with advanced stage III, IVa, or IVb disease and are treated with comprehensive modality including chemotherapy, radiotherapy, and surgery. Despite advancements in treatment modality and technique, noisome recurrence, invasiveness, and resistance as well as posttreatment complications severely influence survival rate and quality of life. Thus, new therapeutic strategies are urgently needed that offer enhanced efficacy with less toxicity. ROS in cancer cells plays a vital role in regulating cell death, DNA repair, stemness maintenance, metabolic reprogramming, and tumor microenvironment, all of which have been implicated in resistance to chemo-/radiotherapy of head and neck cancer. Adjusting ROS generation and elimination to reverse the resistance of cancer cells without impairing normal cells show great hope in improving the therapeutic efficacy of chemo-/radiotherapy of head and neck cancer. In the current review, we discuss the pivotal and targetable redox-regulating system including superoxide dismutases (SODs), tripeptide glutathione (GSH), thioredoxin (Trxs), peroxiredoxins (PRXs), nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/keap1), and mitochondria electron transporter chain (ETC) complexes and their roles in regulating ROS levels and their clinical significance implicated in chemo-/radiotherapy of head and neck cancer. We also summarize several old drugs (referred to as the non-anti-cancer drugs used in other diseases for a long time) and small molecular compounds as well as natural herbs which effectively modulate cellular ROS of head and neck cancer to synergize the efficacy of conventional chemo-/radiotherapy. Emerging interdisciplinary techniques including photodynamic, nanoparticle system, and Bio-Electro-Magnetic-Energy-Regulation (BEMER) therapy are promising measures to broaden the potency of ROS modulation for the benefit of chemo-/radiotherapy in head and neck cancer.

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“…Despite great efforts to improve the treatment of esophageal adenocarcinoma, its 5-year survival rate is still <20% (88,89). In EAC, TXNIP has been confirmed to be an independent prognostic factor for distant metastasis-free survival (90). Studies have indicated that TXNIP overexpression can decrease tumor growth in mice.…”

Section: Txnip and Gastroesophageal Cancermentioning

confidence: 99%

Research Progress of TXNIP as a Tumor Suppressor Gene Participating in the Metabolic Reprogramming and Oxidative Stress of Cancer Cells in Various Cancers

et al. 2020

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Thioredoxin-interacting protein (TXNIP) is a thioredoxin-binding protein that can mediate oxidative stress, inhibit cell proliferation, and induce apoptosis by inhibiting the function of the thioredoxin system. TXNIP is important because of its wide range of functions in cardiovascular diseases, neurodegenerative diseases, cancer, diabetes, and other diseases. Increasing evidence has shown that TXNIP expression is low in tumors and that it may act as a tumor suppressor in various cancer types such as hepatocarcinoma, breast cancer, and lung cancer. TXNIP is known to inhibit the proliferation of breast cancer cells by affecting metabolic reprogramming and can affect the invasion and migration of breast cancer cells through the TXNIP-HIF1α-TWIST signaling axis. TXNIP can also prevent the occurrence of bladder cancer by inhibiting the activation of ERK, which inhibits apoptosis in bladder cancer cells. In this review, we find that TXNIP can be regulated by binding to transcription factors or other binding proteins and can also be downregulated by epigenetic changes or miRNA. In addition, we also summarize emerging insights on TXNIP expression and its functional role in different kinds of cancers, as well as clarify its participation in metabolic reprogramming and oxidative stress in cancer cells, wherein it acts as a putative tumor suppressor gene to inhibit the proliferation, invasion, and migration of different tumor cells as well as promote apoptosis in these cells. TXNIP may therefore be of basic and clinical significance for finding novel molecular targets that can facilitate the diagnosis and treatment of malignant tumors.

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Induction of Thioredoxin-Interacting Protein by a Histone Deacetylase Inhibitor, Entinostat, Is Associated with DNA Damage and Apoptosis in Esophageal Adenocarcinoma

Cited by 22 publications

References 42 publications

PRMT5-TRIM21 interaction regulates the senescence of osteosarcoma cells by targeting the TXNIP/p21 axis

PRMT5-TRIM21 interaction regulates the senescence of osteosarcoma cells by targeting the TXNIP/p21 axis

ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer

Research Progress of TXNIP as a Tumor Suppressor Gene Participating in the Metabolic Reprogramming and Oxidative Stress of Cancer Cells in Various Cancers

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