Dataset Information

HPV⁺ HNSCC-derived exosomal miR-9-5p inhibits TGF-β signaling-mediated fibroblast phenotypic transformation through NOX4.

ABSTRACT: Human papillomavirus (HPV) is a significant risk factor for head and neck squamous cell carcinoma (HNSCC). HPV⁺ HNSCC patients have a higher survival rate, which may be related to its unique tumor microenvironment. Exosomes are emerging as a communication tool between tumor cells and the tumor microenvironment, including cancer-associated fibroblasts (CAFs). In this study, 111 clinical samples tissues and public sequencing data were analyzed. Our study found fewer CAFs infiltrated in HPV⁺ HNSCC, and poor CAF infiltration level was associated with a good prognosis. HPV⁺ HNSCC cell-derived exosomes can significantly reduce the phenotypic transformation of fibroblasts. miR-9-5p, as a miRNA enriched in HPV⁺ HNSCC cell-derived exosomes, can be transferred to fibroblasts. miR-9-5p mimic transfection decreased the expression of NOX4 and the level of intracellular reactive oxygen species (ROS), which inhibited the transforming growth factor beta 1(TGF-β1)-induced increase of αSMA levels. Therefore, these results indicated that HPV⁺ HNSCC-derived exosomal miR-9-5p inhibits TGF-β signaling-mediated fibroblast phenotypic transformation through NOX4, which is related to the excellent prognosis of HPV patients.

SUBMITTER: Wang B

PROVIDER: S-EPMC8990726 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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HPV<sup>+</sup> HNSCC-derived exosomal miR-9-5p inhibits TGF-β signaling-mediated fibroblast phenotypic transformation through NOX4.

Wang Bozhi B Zhang Siwei S Tong Fangjia F Wang Yan Y Wei Lanlan L

Cancer science 20220303 4

Human papillomavirus (HPV) is a significant risk factor for head and neck squamous cell carcinoma (HNSCC). HPV<sup>+</sup> HNSCC patients have a higher survival rate, which may be related to its unique tumor microenvironment. Exosomes are emerging as a communication tool between tumor cells and the tumor microenvironment, including cancer-associated fibroblasts (CAFs). In this study, 111 clinical samples tissues and public sequencing data were analyzed. Our study found fewer CAFs infiltrated in ...[more]

PMID: 35100464

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Project description:IntroductionTreatment-related toxicity following either chemo- or radiotherapy can create significant clinical challenges for HNSCC cancer patients, particularly those with HPV-associated oropharyngeal squamous cell carcinoma. Identifying and characterizing targeted therapy agents that enhance the efficacy of radiation is a reasonable approach for developing de-escalated radiation regimens that result in less radiation-induced sequelae. We evaluated the ability of our recently discovered, novel HPV E6 inhibitor (GA-OH) to radio-sensitize HPV+ and HPV- HNSCC cell lines to photon and proton radiation.MethodsRadiosensitivity to either photon or proton beams was assessed using various assays such as colony formation assay, DNA damage markers, cell cycle and apoptosis, western blotting, and primary cells. Calculations for radiosensitivity indices and relative biological effectiveness (RBE) were based on the linear quadratic model.ResultsOur results showed that radiation derived from both X-ray photons and protons is effective in inhibiting colony formation in HNSCC cells, and that GA-OH potentiated radiosensitivity of the cells. This effect was stronger in HPV+ cells as compared to their HPV- counterparts. We also found that GA-OH was more effective than cetuximab but less effective than cisplatin (CDDP) in enhancing radiosensitivity of HSNCC cells. Further tests indicated that the effects of GA-OH on the response to radiation may be mediated through cell cycle arrest, particularly in HPV+ cell lines. Importantly, the results also showed that GA-OH increases the apoptotic induction of radiation as measured by several apoptotic markers, even though radiation alone had little effect on apoptosis.ConclusionThe enhanced combinatorial cytotoxicity found in this study indicates the strong potential of E6 inhibition as a strategy to sensitize cells to radiation. Future research is warranted to further characterize the interaction of GA-OH derivatives and other E6-specific inhibitors with radiation, as well as its potential to improve the safety and effectiveness of radiation treatment for patients with oropharyngeal cancer.

Dataset Information

HPV⁺ HNSCC-derived exosomal miR-9-5p inhibits TGF-β signaling-mediated fibroblast phenotypic transformation through NOX4.

Publications

HPV<sup>+</sup> HNSCC-derived exosomal miR-9-5p inhibits TGF-β signaling-mediated fibroblast phenotypic transformation through NOX4.

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Dataset Information

HPV+ HNSCC-derived exosomal miR-9-5p inhibits TGF-β signaling-mediated fibroblast phenotypic transformation through NOX4.

Publications

HPV<sup>+</sup> HNSCC-derived exosomal miR-9-5p inhibits TGF-β signaling-mediated fibroblast phenotypic transformation through NOX4.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

HPV⁺ HNSCC-derived exosomal miR-9-5p inhibits TGF-β signaling-mediated fibroblast phenotypic transformation through NOX4.