Inhibition of STAT1 sensitizes radioresistant nasopharyngeal carcinoma cell line CNE-2R to radiotherapy

Qu, Song; Guo, Ya; Huang, Shan; Zhu, Xiao‐Dong

doi:10.18632/oncotarget.19690

Cited by 13 publications

(8 citation statements)

References 17 publications

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“…Instead, STAT1 is highly responsive to the cytosolic content of LINC00669, whose ectopic expression leads to increases in both total and phosphorylated STAT1. Inhibition of STAT1 can enhance the radiosensitivity of CNE-2R cells, and knockout STAT1 causes cell growth retardation and apoptosis both in vitro and in vivo [37]. Therefore, we consider STAT1 as a key effector in LINC00669/SOCS1/JAK-STAT signaling cascade, which compiles cancerous transcriptome in NPC cells.…”

Section: Discussionmentioning

confidence: 99%

LINC00669 insulates the JAK/STAT suppressor SOCS1 to promote nasopharyngeal cancer cell proliferation and invasion

Qiu

Tan

Liu

et al. 2020

J Exp Clin Cancer Res

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Nasopharyngeal carcinoma (NPC) is an epithelial cancer emerging from the lining of nasopharyngeal mucosa, with extremely frequent occurrence in east and southeast Asia. For the purpose of exploring roles of the dysregulated long non-coding RNA (lncRNA) in NPC, we identified a novel lncRNA LINC00669 with an apparent negative correlation to the overall survival from human NPC mRNA expression profiling databases. We further performed RNA pulldown coupled with mass spectrum to find out its target protein, and applied a series of in vitro and in vivo loss-and-gain-of function assays to investigate its oncogenic roles in NPC tumor development and progression. Our results demonstrated that LINC00669 competitively binds to the key JAK/STAT signaling pathway suppressor SOCS1, and insulates it from imposing ubiquitination modification on the pathway component of STAT1, which leads to its abnormal stabilization and activation. The activated STAT1 is then transferred into the nucleus and initiates the transcription of genes related to proliferation and invasion. In summary, our study reveals that the cytoplasmic resident lncRNA LINC00669 confers malignant properties on NPC cancer cells by facilitating a persistent activation of the JAK/STAT signaling pathway. Findings in the current study shed lights on prospects for treating NPC using strategies targeting the novel regulator of the JAK/STAT signaling.

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Section: Discussionmentioning

confidence: 99%

LINC00669 insulates the JAK/STAT suppressor SOCS1 to promote nasopharyngeal cancer cell proliferation and invasion

Qiu

Tan

Liu

et al. 2020

J Exp Clin Cancer Res

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“…ese upregulated genes are closely related to survival mechanisms, such as DNA repair, metabolic changes, tumor recurrence, and malignant transformation [9]. us, controlling the signals associated with radiation-induced resistant genes might be a major strategy in radiotherapy to reduce the irradiation burden in the host [10,11]. For this reason, the discovery of adjuvants targeting radioresistant molecules is important for effective radiotherapy [12,13].…”

Section: Introductionmentioning

confidence: 99%

mTOR-Mediated Antioxidant Activation in Solid Tumor Radioresistance

Woo

Lee

Jung

et al. 2019

Journal of Oncology

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Radiotherapy is widely used for the treatment of cancer patients, but tumor radioresistance presents serious therapy challenges. Tumor radioresistance is closely related to high levels of mTOR signaling in tumor tissues. Therefore, targeting the mTOR pathway might be a strategy to promote solid tumor sensitivity to ionizing radiation. Radioresistance is associated with enhanced antioxidant mechanisms in cancer cells. Therefore, examination of the relationship between mTOR signaling and antioxidant mechanism-linked radioresistance is required for effective radiotherapy. In particular, the effect of mTOR signaling on antioxidant glutathione induction by the Keap1-NRF2-xCT pathway is described in this review. This review is expected to assist in the identification of therapeutic adjuvants to increase the efficacy of radiotherapy.

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“…12 Moreover, the suppression of STAT1 expression reversed tumor radioresistance and malignant progression in renal cell carcinoma 11 and nasopharyngeal cancer. 13 In comparison with other STAT isoforms, STAT1 is the main transcription factor that acts as a critical control point of the phenomenon of therapeutic resistance to ionizing radiation (IR) in different types of cancer cells. Thus, understanding the mechanisms of the interaction between the IFN/STAT1 pathway and cancer cells could lead to the development of highly tailored radio-immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

<p>Targeting IFN/STAT1 Pathway as a Promising Strategy to Overcome Radioresistance</p>

Liu

Imani

Deng

et al. 2020

OTT

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The interferon (IFN)-mediated activation of the Janus kinase (JAK)-signal transducer and activator of transcription 1 (STAT1) signaling is crucial for cell sensitivity to ionizing radiation. Several preclinical studies have reported that the IFN/STAT1 pathway mediates radioresistance in the tumor microenvironment by shielding the immune responses and activating survival signaling pathways. This review focuses on the oncogenic function of the IFN/STAT1 pathway, emphasizing the major signaling pathway in radiation sensitization. Furthermore, it highlights the possibility of mediatory roles of the IFN/STAT1 pathway as a prognostic therapeutic target in the modulation of resistance to radiotherapy and chemotherapy. MicroRNA involved in the regulation of the IFN/STAT1 pathway is also discussed. A better understanding of radiation-induced IFN/STAT1 signaling will open new opportunities for the development of novel therapeutic strategies, as well as define new approaches to enhance radio-immunotherapy efficacy in the treatment of various types of cancers.

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Inhibition of STAT1 sensitizes radioresistant nasopharyngeal carcinoma cell line CNE-2R to radiotherapy

Cited by 13 publications

References 17 publications

LINC00669 insulates the JAK/STAT suppressor SOCS1 to promote nasopharyngeal cancer cell proliferation and invasion

LINC00669 insulates the JAK/STAT suppressor SOCS1 to promote nasopharyngeal cancer cell proliferation and invasion

mTOR-Mediated Antioxidant Activation in Solid Tumor Radioresistance

<p>Targeting IFN/STAT1 Pathway as a Promising Strategy to Overcome Radioresistance</p>

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