MiR-526b-3p通过抑制外泌体LAMP3介导的自噬增强头颈部鳞状细胞癌细胞对放疗的敏感性。

IF 3.3 4区 医学 Q3 IMMUNOLOGY Autoimmunity Pub Date : 2023-12-01 Epub Date: 2023-09-23 DOI:10.1080/08916934.2023.2259125
Huixiang Lu, Junnian Zhou, Xiaojun Li, Xiaoqin Han, Shuping Ma, Chunlan Feng
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引用次数: 0

摘要

据报道,溶体相关膜蛋白3(LAMP3)通过调节肿瘤细胞自噬,在多种癌症类型中是肿瘤启动子。然而,LAMP3在头颈部鳞状细胞癌(HNSCC)放射抵抗中的潜在机制尚不清楚。因此,我们目前的研究旨在检测LAMP3对HNSCC细胞放疗耐药性的影响,同时探讨其功能机制。通过RT-Qpcr检测,与辐射敏感的HNSCC细胞系相比,LAMP3在辐射抗性HNSCC细胞株中的表达水平显著较高。包括CCK-8、集落形成和Transwell测定在内的功能测定表明,LAMP3通过诱导自噬促进HNSCC细胞生长来增强无线电抗性。此外,耐辐射的HNSCC细胞可以转移外泌体LAMP3,以提高LAMP3在辐射敏感的HNSCC中的表达。从机制上讲,微小RNA(miRNA)miR-526b-3p可以抑制LAMP3的表达,从而增强HNSCC细胞对放疗的敏感性。总之,外泌体LAMP3的表达通过诱导自噬促进HNSCC细胞的放射抗性,而miR-526b-3p可以靶向抑制这种作用。
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MiR-526b-3p enhances sensitivity of head and neck squamous cell carcinoma cells to radiotherapy via suppressing exosomal LAMP3-mediated autophagy.

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.

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来源期刊
Autoimmunity
Autoimmunity 医学-免疫学
CiteScore
5.70
自引率
8.60%
发文量
59
审稿时长
6-12 weeks
期刊介绍: Autoimmunity is an international, peer reviewed journal that publishes articles on cell and molecular immunology, immunogenetics, molecular biology and autoimmunity. Current understanding of immunity and autoimmunity is being furthered by the progress in new molecular sciences that has recently been little short of spectacular. In addition to the basic elements and mechanisms of the immune system, Autoimmunity is interested in the cellular and molecular processes associated with systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, type I diabetes, multiple sclerosis and other systemic and organ-specific autoimmune disorders. The journal reflects the immunology areas where scientific progress is most rapid. It is a valuable tool to basic and translational researchers in cell biology, genetics and molecular biology of immunity and autoimmunity.
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