通过抑制exosomal LAMP3介导的自噬,miR-526b-3p增强了头颈部鳞状细胞癌细胞对放疗的敏感性。
MiR-526b-3p enhances sensitivity of head and neck squamous cell carcinoma cells to radiotherapy via suppressing exosomal LAMP3-mediated autophagy.
发表日期:2023 Dec
作者:
Huixiang Lu, Junnian Zhou, Xiaojun Li, Xiaoqin Han, Shuping Ma, Chunlan Feng
来源:
Cellular & Molecular Immunology
摘要:
溶酶体相关膜蛋白3(LAMP3)已被报道在多种癌症类型中通过调节肿瘤细胞自噬作为肿瘤促进因子。然而,LAMP3在头颈鳞状细胞癌(HNSCC)放射耐受性中的潜在机制尚不清楚。因此,我们当前的研究旨在检测LAMP3对HNSCC细胞对放射治疗的耐受影响,并同时探索其功能机制。通过RT-Qpcr检测,发现与放射敏感的HNSCC细胞系相比,辐射耐受的HNSCC细胞系中LAMP3表达水平显著升高。包括CCK-8、集落形成和Transwell实验在内的功能分析表明,LAMP3通过诱导自噬促进HNSCC细胞生长,从而增强耐放射治疗能力。此外,耐放射的HNSCC细胞能够通过外泌体转移LAMP3来提高放射敏感的HNSCC细胞中LAMP3的表达水平。在机制上,微小RNA(miRNA)miR-526b-3p能够抑制LAMP3表达,从而增强HNSCC细胞对放射治疗的敏感性。总之,外泌体中LAMP3的表达通过诱导自噬促进HNSCC细胞的放射耐受性,而miR-526b-3p可以有针对性地抑制这种效应。
Lysosomal associated membrane protein 3 (LAMP3) has been reported to be a tumour promoter in multiple cancer types by modulating tumour cell autophagy. However, the potential mechanism of LAMP3 in radio-resistance of head and neck squamous cell carcinoma (HNSCC) remains unknown. Therefore, our current study aims to detect the impacts of LAMP3 on the resistance of HNSCC cells to radiotherapy and meanwhile explore its functional mechanism. Through RT-Qpcr examination, LAMP3 expression was identified to be expressed at a significantly high level in irradiation-resistant HNSCC cell lines compared with irradiation-sensitive HNSCC cell lines. Functional assays including CCK-8, colony formation and Transwell assays demonstrated that LAMP3 enhanced the radio-resistance through inducing autophagy to promote HNSCC cell growth. Furthermore, irradiation-resistant HNSCC cells could transfer exosomal LAMP3 to elevate LAMP3 expression in irradiation-sensitive HNSCC cells. Mechanistically, microRNA (miRNA) miR-526b-3p could inhibit LAMP3 expression so as to strengthen sensitivity of HNSCC cells to radiotherapy. In a word, exosomal LAMP3 expression promoted radioresistance of HNSCC cells via inducing autophagy, while this effect could be suppressed by miR-526b-3p in a targeted manner.