Dataset Information

Twist1 promotes radioresistance in nasopharyngeal carcinoma.

ABSTRACT: With the development of advanced imaging and radiation technologies, radiotherapy has been employed as the principal treatment approach for nasopharyngeal carcinoma (NPC). So far, a number of patients still suffer from the failure of this treatment due to the acquired radioresistance, but the underlying mechanisms are still poorly defined. In this study, we found that Twist1, participating in a variety of cell biological process, was associated with the malignancy of NPC and could induce NPC radioresistance in vitro and in vivo. Mechanically, Twist1 could promote the accumulation of DNA damage repair and inhibit the apoptosis of NPC cells. Therefore, our study not only elucidates the significant role of Twist1 in radioresistance of NPC, but also highlights Twist1 as a potential therapeutic target for NPC.

SUBMITTER: Zhang L

PROVIDER: S-EPMC5348396 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Twist1 promotes radioresistance in nasopharyngeal carcinoma.

Zhang Linli L Su Beibei B Sun Wei W Li Wenwen W Luo Min M Liu Dongbo D Mei Qi Q Long Guoxian G Hu Guangyuan G Hu Guoqing G

Oncotarget 20161201 49

With the development of advanced imaging and radiation technologies, radiotherapy has been employed as the principal treatment approach for nasopharyngeal carcinoma (NPC). So far, a number of patients still suffer from the failure of this treatment due to the acquired radioresistance, but the underlying mechanisms are still poorly defined. In this study, we found that Twist1, participating in a variety of cell biological process, was associated with the malignancy of NPC and could induce NPC rad ...[more]

PMID: 27793033

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Project description:BackgroundRadiotherapy is the primary treatment for patients with nasopharyngeal carcinoma (NPC); however, almost 20% of patients experience treatment failure due to radioresistance. Therefore, understanding the mechanisms of radioresistance is imperative. HOTAIRM1 is deregulated in various human cancers, yet its role in NPC radioresistance are largely unclear.MethodsThis study investigated the association between HOTAIRM1 and radioresistance using CCK8, flow cytometry, and comet assays. Additionally, xenograft mice and patient-derived xenografts (PDX) models were employed to elucidate the biological functions of HOTAIRM1, and transcriptomic RNA sequencing was utilized to identify its target genes.ResultsOur study revealed an upregulation of HOTAIRM1 levels in radioresistant NPC cell lines and tissues. Furthermore, a positive correlation was noted between high HOTAIRM1 expression and increased NPC cell proliferation, reduced apoptosis, G2/M cell cycle arrest, and diminished cellular DNA damage following radiotherapy. HOTAIRM1 modulates the acetylation and stability of the FTO protein, and inhibiting FTO elevates the m6A methylation level of CD44 precursor transcripts in NPC cells. Additionally, silencing the m6A reading protein YTHDC1 was found to increase the expression of CD44V. HOTAIRM1 enhances NPC cell resistance to ferroptosis and irradiation through the HOTAIRM1-FTO-YTHDC1-CD44 axis. Mechanistically, HOTAIRM1 interacts with the FTO protein and induces m6A demethylation of the CD44 transcript. The absence of m6A modification in the CD44 transcript prevents its recognition by YTHDC1, resulting in the transition from CD44S to CD44V. An abundance of CD44V suppresses ferroptosis induced by irradiation and contributes to NPC radioresistance.ConclusionsIn conclusion, the results in this study support the idea that HOTAIRM1 stimulates CD44 alternative splicing via FTO-mediated demethylation, thereby attenuating ferroptosis induced by irradiation and promoting NPC radioresistance.

Dataset Information

Twist1 promotes radioresistance in nasopharyngeal carcinoma.

Publications

Twist1 promotes radioresistance in nasopharyngeal carcinoma.

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