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

Cancer Lett. 2022 Apr 10:531:14-26. doi: 10.1016/j.canlet.2022.01.019. Epub 2022 Jan 29.

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.

Keywords: ATG10; ATG16L1; Autophagy; Let-7i-5p; Nasopharyngeal carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Neoplasms* / pathology
  • Phenotype

Substances

  • MicroRNAs