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Targeting USP22 with miR‑30‑5p to inhibit the hypoxia‑induced expression of PD‑L1 in lung adenocarcinoma cells.
Oncology Reports ( IF 3.8 ) Pub Date : 2021-08-13 , DOI: 10.3892/or.2021.8166
Xiaoyang Hua 1 , Heng Chu 1 , Chuanxiao Wang 1 , Xuexin Shi 1 , Ailin Wang 1 , Zhe Zhang 1
Affiliation  

Lung cancer is one of the most common forms of cancer and accounts for a significant proportion of all cancer‑related deaths. Lung adenocarcinoma (LUAD) accounts for approximately 40% of all cases of lung cancer. In recent years, new developments in both the diagnosis and treatment of LUAD have been achieved. Unfortunately, the prognosis remains poor for patients with malignant LUAD. Hypoxia is a common characteristic of solid tumors and induce the immune evasion by increasing the expression of programmed cell death‑ligand‑1 (PD‑L1) in the tumor. In this study, it was predicted that ubiquitin‑specific peptidase 22 (USP22) is the direct target of the microRNA (miR)‑30‑5p family, including miR‑30a‑5p, miR‑30b‑5p, miR‑30c‑5p, miR‑30d‑5p and miR‑30e‑5p. Furthermore, the binding of USP22 with the miR‑30‑5p family was confirmed by luciferase assay. In addition, it was demonstrated that targeting USP22 via the miR‑30‑5p family inhibited the induction of PD‑L1 expression in hypoxic conditions, thus preventing activated T cells from killing LUAD cells. Our results indicated that miR‑30a‑5p, miR‑30b‑5p, miR‑30c‑5p, miR‑30d‑5p and miR‑30e‑5p represent new targets for the treatment of LUAD.

中文翻译:

用 miR-30-5p 靶向 USP22 抑制缺氧诱导的肺腺癌细胞中 PD-L1 的表达。

肺癌是最常见的癌症形式之一,在所有与癌症相关的死亡人数中占很大比例。肺腺癌 (LUAD) 约占所有肺癌病例的 40%。近年来,LUAD的诊断和治疗都取得了新的进展。不幸的是,恶性 LUAD 患者的预后仍然很差。缺氧是实体瘤的一个共同特征,它通过增加肿瘤中程序性细胞死亡配体 1 (PD-L1) 的表达来诱导免疫逃避。在本研究中,预测泛素特异性肽酶 22 (USP22) 是 microRNA (miR)-30-5p 家族的直接靶点,包括 miR-30a-5p、miR-30b-5p、miR-30c-5p , miR-30d-5p 和 miR-30e-5p。此外,荧光素酶测定证实了 USP22 与 miR-30-5p 家族的结合。此外,已证明通过 miR-30-5p 家族靶向 USP22 可抑制缺氧条件下 PD-L1 表达的诱导,从而防止活化的 T 细胞杀死 LUAD 细胞。我们的结果表明,miR-30a-5p、miR-30b-5p、miR-30c-5p、miR-30d-5p和miR-30e-5p代表了治疗LUAD的新靶点。
更新日期:2021-08-13
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