Статья

ADAR1-regulated miR-142-3p/RIG-I axis suppresses antitumor immunity in nasopharyngeal carcinoma

Haoyuan XuDepartment of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, 200031, ChinaWanpeng LiDepartment of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, 200031, ChinaKai XueDepartment of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, 200031, ChinaHuankang ZhangDepartment of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, 200031, ChinaHan LiDepartment of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, 200031, ChinaHaoran YuDepartment of Otorhinolaryngology-Head and Neck Surgery, Affiliated Zhongshan Hospital, Fudan University, Shanghai, 200030, ChinaHu LiDepartment of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, 200031, ChinaYurong GuDepartment of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, 200031, ChinaHouyong LiDepartment of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, 200031, ChinaXicai SunDepartment of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, 200031, ChinaQuan LiuDepartment of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, 200031, ChinaDehui WangDepartment of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, 200031, China

2024en

ABI

Аннотация

Following the initial treatment of nasopharyngeal carcinoma (NPC), tumor progression often portends an adverse prognosis for these patients. MicroRNAs (miRNAs) have emerged as critical regulators of tumor immunity, yet their intricate mechanisms in NPC remain elusive. Through comprehensive miRNA sequencing, tumor tissue microarrays and tissue samples analysis, we identified miR-142-3p as a significantly upregulated miRNA that is strongly associated with poor prognosis in recurrent NPC patients. To elucidate the underlying molecular mechanism, we employed RNA sequencing, coupled with cellular and tissue assays, to identify the downstream targets and associated signaling pathways of miR-142-3p. Our findings revealed two potential targets, CFL2 and WASL, which are directly targeted by miR-142-3p. Functionally, overexpressing CFL2 or WASL significantly reversed the malignant phenotypes induced by miR-142-3p both in vitro and in vivo. Furthermore, signaling pathway analysis revealed that miR-142-3p repressed the RIG-I-mediated immune defense response in NPC by inhibiting the nuclear translocation of IRF3, IRF7 and p65. Moreover, we discovered that ADAR1 physically interacted with Dicer and promoted the formation of mature miR-142-3p in a dose-dependent manner. Collectively, ADAR1-mediated miR-142-3p processing promotes tumor progression and suppresses antitumor immunity, indicating that miR-142-3p may serve as a promising prognostic biomarker and therapeutic target for NPC patients.

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Идентификаторы

DOI: 10.1016/j.ncrna.2024.08.003

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar