Ribosomal DNA as DAMPs Signal for MCF7 Cancer Cells

Malinovskaya, Elena M.; Ershova, Elizaveta S.; Okorokova, N. A.; Вейко, В. П.; Konkova, Marina S.; Kozhina, Ekaterina A.; Savinova, Ekaterina A.; Porokhovnik, Lev N.; Kutsev, Serguey I.; Вейко, Н. Н.; Kostyuk, Svetlana V.

doi:10.3389/fonc.2019.00445

Cited by 8 publications

(10 citation statements)

References 58 publications

(72 reference statements)

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“…Breast cancer is one of the tumor types where BIRC3 has not yet fully characterized. In this setting, BIRC3 is regarded as an oncogene with antiapoptotic functions, at the same fashion of Bcl2L1 , Bcl2A1 , RelB , Bcl3 and MDM2 [ 57 , 58 ]. BIRC3 results also upregulated by the administration of the inflammatory cytokine 1β (IL-1β) to MCF-7 breast cancer cell line [ 59 ].…”

Section: The Role Of Birc3 During Evasion Of Cancer Cells From Apoptomentioning

confidence: 99%

BIRC3 and BIRC5: multi‐faceted inhibitors in cancer

Frazzi

2021

Cell Biosci

126

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Background The evasion from apoptosis is a common strategy adopted by most tumors, and inhibitors of apoptosis proteins (IAPs) are among the most studied molecular and therapeutic targets. BIRC3 (cellular IAP2) and BIRC5 (survivin) are two of the eight members of the human IAPs family. This family is characterized by the presence of the baculoviral IAP repeat (BIR) domains, involved in protein-protein interactions. In addition to the BIR domains, IAPs also contain other important domains like the C-terminal ubiquitin-conjugating (UBC) domain, the caspase recruitment (CARD) domain and the C-terminal Ring zinc-finger (RING) domain. Main body BIRC3 and BIRC5 have been characterized in some solid and hematological tumors and are therapeutic targets for the family of drugs called “Smac mimetics”. Many evidences point to the pro-survival and antiapoptotic role of BIRC3 in cancer cells, however, not all the data are consistent and the resulting picture is heterogeneous. For instance, BIRC3 genetic inactivation due to deletions or point mutations is consistently associated to shorter progression free survival and poor prognosis in chronic lymphocytic leukemia patients. BIRC3 inactivation has also been associated to chemoimmunotherapy resistance. On the contrary, the progression from low grade gliomas to high grade gliomas is accompanied by BIRC3 expression increase, which bears relevant prognostic consequences. Due to the relationship between BIRC3, MAP3K14 and the non-canonical NF-kB pathway, BIRC3 inactivation bears consequences also on the tumor cells relying on NF-kB pathway to survive. BIRC5, on the contrary, is commonly considered an anti-apoptotic molecule, promoting cell division and tumor progression and it is widely regarded as potential therapeutic target. Conclusions The present manuscript collects and reviews the most recent literature concerning the role played by BIRC3 and BIRC5 in cancer cells, providing useful information for the choice of the best therapeutic targets.

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Section: The Role Of Birc3 During Evasion Of Cancer Cells From Apoptomentioning

confidence: 99%

BIRC3 and BIRC5: multi‐faceted inhibitors in cancer

Frazzi

2021

Cell Biosci

126

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“…Nazaretyan A.S. 1,3 , Malinovskaya E.M. 1 , Filev A.D. 1,2 , Ershova E.S. 1,2 , Veiko N.N. 1 , Pisarev V.M.…”

Section: Oxidized Extracellular Dna Affects Dna Damage and Transcription Of Genes Regulating Dna Repair And Apoptosis In Human Astrocytomunclassified

“…2 , Khalansky A.S. 4 , Kameneva L.V. 1 , Tabakov V.Y. 1 The effects of oxidized extracellular DNA (oecDNA) on genomic DNA damage and activation of transcription of genes regulating DNA repair and apoptosis in human astrocytoma 1321NI cells were studied.…”

Section: Oxidized Extracellular Dna Affects Dna Damage and Transcription Of Genes Regulating Dna Repair And Apoptosis In Human Astrocytommentioning

confidence: 99%

“…1 , Tabakov V.Y. 1 The effects of oxidized extracellular DNA (oecDNA) on genomic DNA damage and activation of transcription of genes regulating DNA repair and apoptosis in human astrocytoma 1321NI cells were studied. OecDNA fragments, 50-100 ng/ml, were added to 1321NI cells for 0.5-24 hours.…”

Section: Oxidized Extracellular Dna Affects Dna Damage and Transcription Of Genes Regulating Dna Repair And Apoptosis In Human Astrocytommentioning

confidence: 99%

“…Молекулярные механизмы, обеспечивающие резистентность опухоли к лечению, недостаточно изучены. Ранее в наших исследованиях было показано, что фрагменты внеклеточной ДНК (вкДНК) и окисленной вкДНК (овкДНК) могут проникать в раковые клетки и активировать сигнальные каскады адаптивного ответа [1,2]. Мы предположили, что противоопухолевая терапия, вызывающая окислительный стресс и гибель клеток как самой опухоли, так и окружающих тканей, приводит к высвобождению в межклеточное пространство овкДНК.…”

Section: Oxidized Extracellular Dna Affects Dna Damage and Transcription Of Genes Regulating Dna Repair And Apoptosis In Human Astrocytomunclassified

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Oxidized extracellular DNA affects DNA damage and transcription of genes regulating DNA repair and apoptosis in human astrocytoma cells

Назаретян¹,

Малиновская²,

Filev³

et al. 2020

Nauchno-Prakticheskii Zhurnal «Medicinskaia Genetika»

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В работе исследовали влияние окисленной внеклеточной ДНК (овкДНК) на повреждение геномной ДНК и активацию транскрипции генов, регулирующих репарацию ДНК и процессы апоптоза в клетках астроцитомы человека линии 1321NI. Фрагменты овкДНК добавляли в среду культивирования клеток в концентрации 50-100 нг/мл на 0,5-24 часа. Уровни окислительных повреждений и двунитевых разрывов ДНК ядер, экспрессии белков BCL2, BAX определяли с помощью антител к 8-окси-7,8-дигидрогуанозину (8oxodG), фосфорилированной форме гистона H2AX (γH2AX), белкам BCL2 и BAX, соответственно, используя метод проточной цитофлуориметрии. Уровень экспрессии генов BCL2, ВАХ, BRCA1, BRCA2, ТВР (контроль) оценивали методом ПЦР в реальном времени. Воздействие на клетки 1321NI 50-100 нг/мл овкДНК в течение 30-60 мин приводило к 2-4-кратному повышению уровня 8-охоdG (р < 0,01, уровень двунитевых разрывов увеличивался в 3-3,5 раза (р < 0,01), а экспрессия генов репарации повреждений BRCA1 и BRCA2 возрастала в 3-5 раз (р<0,001). Позже, через 5-24 часа после воздействия на клетки овкДНК, в 3,5-5 раз увеличивалось отношение экспрессии генов BCL2/BAX по сравнению с нестимулированными культурами (p<0,001). Таким образом, в клетках астроцитомы овкДНК индуцирует и перестройку генома, и адаптивные реакции транскриптома, c последующей активацией анти-апоптотического процесса в клетках. Предполагается, что тем самым овкДНК может способствовать накоплению резистентных к лечению мутантных клонов в резидуальной опухоли, провоцируя рецидивы. The effects of oxidized extracellular DNA (oecDNA) on genomic DNA damage and activation of transcription of genes regulating DNA repair and apoptosis in human astrocytoma 1321NI cells were studied. OecDNA fragments, 50-100 ng/ml, were added to 1321NI cells for 0.5-24 hours. The levels of oxidative damage and double stranded DNA breaks, BCL and BAX protein expression were determined using antibodies to 8-hydroxy-7,8-dihydroguanosine (8-ohdG), phosphorylated histone γH2AX, BCL2 and BAX proteins and flow cytofluorimetry. The levels of gene expression of BCL2, BAC, BRCA1, BRCA2, TBP (control) were evaluated by real-time PCR. The exposure of 1321NI cells to oecDNA resulted in a 2-4-fold increased levels of 8-ohdG (p <0.01) and 3-3.5-fold increases in double-strand breaks (p < 0.01), whereas the expression of damage repair genes BRCA1 and BRCA2 was enchanced by 3-5 times (p <0.001). In 5-24 hours after exposure to oecDNA cells, the ratio of BCL2/BAX gene expression increased by 3.5-5 times vs. unexposed cell cultures (p <0.001). Therefore, in astrocytoma cells, oecDNA induces both genome rearrangement and adaptive transcriptome reactions followed by activation of an anti-apoptotic path in malignant cells. It is suggested that oecDNA contributes to the accumulation in a residual tumor of mutant clones resistant to treatment thus provoking relapse.

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The complex role of AIM2 in autoimmune diseases and cancers

Zhu

Zhao

Chang

et al. 2021

Immunity Inflam & Disease

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Absent in melanoma 2 (AIM2) is a novel member of interferon (IFN)‐inducible PYHIN proteins. In innate immune cells, AIM2 servers as a cytoplasmic double‐stranded DNA sensor, playing a crucial role in the initiation of the innate immune response as a component of the inflammasome. AIM2 expression is increased in patients with systemic lupus erythematosus (SLE), psoriasis, and primary Sjogren's syndrome, indicating that AIM2 might be involved in the pathogenesis of autoimmune diseases. Meanwhile, AIM2 also plays an antitumorigenesis role in an inflammasome independent‐manner. In melanoma, AIM2 is initially identified as a tumor suppressor factor. However, AIM2 is also found to contribute to lung tumorigenesis via the inflammasome‐dependent release of interleukin 1β and regulation of mitochondrial dynamics. Additionally, AIM2 reciprocally dampening the cGAS‐STING pathway causes immunosuppression of macrophages and evasion of antitumor immunity during antibody treatment. To summarize the complicated effect and role of AIM2 in autoimmune diseases and cancers, herein, we provide an overview of the emerging research progress on the function and regulatory pathway of AIM2 in innate and adaptive immune cells, as well as tumor cells, and discuss its pathogenic role in autoimmune diseases, such as SLE, psoriasis, primary Sjogren's syndrome, and cancers, such as melanomas, non‐small‐cell lung cancer, colon cancer, hepatocellular carcinoma, renal carcinoma, and so on, hopefully providing potential therapeutic and diagnostic strategies for clinical use.

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Ribosomal DNA as DAMPs Signal for MCF7 Cancer Cells

Cited by 8 publications

References 58 publications

BIRC3 and BIRC5: multi‐faceted inhibitors in cancer

BIRC3 and BIRC5: multi‐faceted inhibitors in cancer

Oxidized extracellular DNA affects DNA damage and transcription of genes regulating DNA repair and apoptosis in human astrocytoma cells

The complex role of AIM2 in autoimmune diseases and cancers

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