TRAF2 Knockdown in Nasopharyngeal Carcinoma Induced Cell Cycle Arrest and Enhanced the Sensitivity to Radiotherapy

Zhu, Hongyuan; Ding, Wei; Wu, Jiaojiao; Ma, Rongyou; Pan, Zhaohu; Mao, Xin-Li

doi:10.1155/2020/1641340

Cited by 5 publications

(4 citation statements)

References 26 publications

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“…Moreover, it has been confirmed that radiotherapy could induce a G0/G1 cell cycle arrest and pro-apoptotic effect in EC [42,43], nasopharyngeal carcinoma [44], meningiomas [45], and breast cancer [46]. Our results corroborate these findings, which revealed that KYSE30 and KYSE510 cells showed cell cycle arrest at the G0/G1 phase after radiotherapy, and this cell cycle arrest was weakened after overexpressed HMGB1.…”

Section: Discussionsupporting

confidence: 86%

HMGB1 overexpression promotes a malignant phenotype and radioresistance in ESCC

Dong¹,

Zhang²,

Du³

et al. 2022

J. Cancer

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Esophageal cancer is a common malignant disease that is generally treated with radiotherapy. High mobility group box 1 (HMGB1) plays an essential role in tumor cell proliferation, migration, and cell cycle progression. Here, we aimed to clarify the effects of HMGB1 on radioresistance in esophageal squamous cell carcinoma (ESCC) cell lines and patient survival. We performed immunohistochemistry for HMGB1 in biopsy samples of 39 stage I-III ESCC patients grouped by HMGB1 expression status. Then, 1-, 3-, 5-, and 10-year overall survival outcomes were calculated by Kaplan-Meier survival analysis. The cellular localization of HMGB1 was examined before and after irradiation by Immunofluorescence staining. Stable cell lines (KYSE30 and KYSE510) with differential HMGB1 expression were constructed using lentiviruses. Furthermore, we examined phosphorylated histone H2AX (γ-H2AX) expression in both HMGB1 overexpression and negative control groups by western blotting. HMGB1-negative expression was associated with superior ESCC patient 10-year survival (P=0.016). HMGB1 overexpression promoted cell migration, proliferation, and radioresistance and mitigated cell cycle arrest at the G0/G1 phase induced by irradiation. This demonstrates that HMGB1-positive expression is correlated with unfavorable clinical outcomes, and HMGB1 overexpression may promote the malignant phenotype of ESCC cells and induce radioresistance by regulating cell cycle distribution in ESCC.

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Section: Discussionsupporting

confidence: 86%

HMGB1 overexpression promotes a malignant phenotype and radioresistance in ESCC

Dong¹,

Zhang²,

Du³

et al. 2022

J. Cancer

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“…In addition, the investigation performed by Zhu et al indicated that blockade of the HGF/c-Met pathway would result in restrained radioresistance and augmented cell apoptosis in human non-small-cell lung cancer [ 29 ]. Moreover, another prior study illustrated that EGF silencing sensitized NPC cells to radiotherapy [ 30 ]. Similarly, EGFR downregulation was previously shown to accelerate the radiosensitivity of NPC cells [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Tumor-derived extracellular vesicles inhibit HGF/c-Met and EGF/EGFR pathways to accelerate the radiosensitivity of nasopharyngeal carcinoma cells via microRNA-142-5p delivery

2022

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Radioresistance prevails as one of the largest obstacles in the clinical treatment of nasopharyngeal carcinoma (NPC). Meanwhile, tumor-derived extracellular vesicles (TEVs) possess the ability to manipulate radioresistance in NPC. However, its mechanism remains to be further explored. Therefore, the current study set out to explore the mechanism of microRNA (miR)-142-5p delivered by TEVs in regard to the radiosensitivity of NPC. Firstly, peripheral blood samples were collected from patients with radioresistance and radiosensitivity, followed by RT-qPCR detection of miR-142-5p expression. A dual-luciferase reporter assay was carried out to elucidate the targeting relationship of miR-142-5p with HGF and EGF. In addition, radiotherapy-resistant NPC cell models were established by screening NPC cells with gradient increasing radiation exposure, and co-incubated with EVs isolated from miR-142-5p mimic-transfected NPC cells, followed by overexpression of HGF and EGF. Moreover, cell viability was detected by means of MTS, cell proliferation with a colony formation assay, cell apoptosis with flow cytometry, and expression patterns of related genes with the help of Western blot analysis. NPC xenotransplantation models in nude mice were also established by subcutaneous injection of 5-8FR cells to determine apoptosis, tumorigenicity, and radiosensitivity in nude mice. It was found that miR-142-5p was poorly expressed in peripheral blood from NPC patients with radioresistance. Mechanistic experimentation illustrated that miR-142-5p inversely targeted HGF and EGF to inactivate the HGF/c-Met and EGF/EGFR pathways, respectively. NPC cell apoptosis was observed to be augmented, while their radioresistance and proliferation were restricted by EVs-miR-142-5p or HGF silencing, or EGF silencing. Furthermore, EVs-miR-142-5p inhibited growth and radioresistance and accelerated the apoptosis of radiotherapy-resistant NPC cells in nude mice by inhibiting the HGF/c-Met and EGF/EGFR pathways. Collectively, our findings indicated that TEVs might inhibit the HGF/c-Met and EGF/EGFR pathways by delivering miR-142-5p into radiotherapy-resistant NPC cells to enhance radiosensitivity in NPC.

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“…TRAF2 is a member of the TNF-receptor-associated factor family. It acts as a mediator of TNF-induced signaling [ 46 , 47 , 48 ]. Overexpression of TRAF2 enhances the malignant phenotype of gastric cancer cells [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…Overexpression of TRAF2 enhances the malignant phenotype of gastric cancer cells [ 47 ]. In nasopharyngeal carcinoma cells, overexpression of TRAF2 promotes cancer cell proliferation and anchorage-independent growth [ 48 ]. Importantly, its overexpression was associated with resistance to irradiation [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Super-Enhancer-Based Analysis: Identification of Prognostic Genes in Oral Squamous Cell Carcinoma

Saito

Asai

Tanaka

et al. 2022

IJMS

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Advanced-stage oral squamous cell carcinoma (OSCC) patients are treated with combination therapies, such as surgery, radiation, chemotherapy, and immunotherapy. However, OSCC cells acquire resistance to these treatments, resulting in local recurrence and distant metastasis. The identification of genes involved in drug resistance is essential for improving the treatment of this disease. In this study, we applied chromatin immunoprecipitation sequencing (ChIP-Seq) to profile active enhancers. For that purpose, we used OSCC cell lines that had been exposed to cetuximab for a prolonged period. In total, 64 chromosomal loci were identified as active super-enhancers (SE) according to active enhancer marker histone H3 lysine 27 acetylation (H3K27ac) ChIP-Seq. In addition, a total of 131 genes were located in SE regions, and 34 genes were upregulated in OSCC tissues by TCGA-OSCC analysis. Moreover, high expression of four genes (C9orf89; p = 0.035, CENPA; p = 0.020, PISD; p = 0.0051, and TRAF2; p = 0.0075) closely predicted a poorer prognosis for OSCC patients according to log-rank tests. Increased expression of the four genes (mRNA Z-score ≥ 0) frequently co-occurred in TCGA-OSCC analyses. The high and low expression groups of the four genes showed significant differences in prognosis, suggesting that there are clear differences in the pathways based on the underlying gene expression profiles. These data indicate that potential stratified therapeutic strategies could be used to overcome resistance to drugs (including cetuximab) and further improve responses in drug-sensitive patients.

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TRAF2 Knockdown in Nasopharyngeal Carcinoma Induced Cell Cycle Arrest and Enhanced the Sensitivity to Radiotherapy

Cited by 5 publications

References 26 publications

HMGB1 overexpression promotes a malignant phenotype and radioresistance in ESCC

HMGB1 overexpression promotes a malignant phenotype and radioresistance in ESCC

Tumor-derived extracellular vesicles inhibit HGF/c-Met and EGF/EGFR pathways to accelerate the radiosensitivity of nasopharyngeal carcinoma cells via microRNA-142-5p delivery

Genome-Wide Super-Enhancer-Based Analysis: Identification of Prognostic Genes in Oral Squamous Cell Carcinoma

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