Let-7i-5p promotes a malignant phenotype in nasopharyngeal carcinoma via inhibiting tumor-suppressive autophagy

Let-7i-5p 通过抑制肿瘤抑制自噬促进鼻咽癌的恶性表型

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作者:Bo You, Panpan Zhang, Miao Gu, Haimeng Yin, Yue Fan, Hui Yao, Si Pan, Haijing Xie, Tianyi Cheng, Huiting Liu, Yiwen You, Jisheng Liu

Abstract

MicroRNAs (miRNAs) regulate gene expression to participate in carcinogenesis and tumor progression. Therefore, identification of a malignant phenotype associated with miRNAs and therapeutic targets will contribute substantially in improving nasopharyngeal carcinoma (NPC) treatment. In this study, we demonstrated that overexpression of let-7i-5p promotes the malignant phenotype by acting as an autophagy suppressor by targeting ATG10 and ATG16L1 in NPC. Expression levels of let-7i-5p were markedly increased in NPC and head and neck cancers based on an analysis of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Using a cohort comprising 150 NPC tissues, we found that let-7i-5p was correlated with advanced stage, recurrence, metastasis, lymph node metastasis, and poor clinical outcomes. In addition to a series of in vitro cellular analyses, in vivo mouse tumor models revealed that let-7i-5p inhibits autophagy and promotes the malignant phenotype of NPC by targeting ATG10 and ATG16L1. Our findings demonstrate that let-7i-5p may represent a promising therapeutic target for NPC treatment.

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