MiR-138-5p suppresses the progression of lung cancer by targeting SNIP1

Thorac Cancer. 2023 Feb;14(6):612-623. doi: 10.1111/1759-7714.14791. Epub 2023 Jan 3.

Abstract

Background: MicroRNAs (miRNAs) play crucial roles in the development of various cancers. Here, we aimed to evaluate the roles of miR-138-5p in lung cancer progression and the value of miR-138-5p in lung cancer diagnosis.

Methods: Quantitative real-time PCR was performed to examine the expressions of miR-138-5p and smad nuclear interacting protein 1 (SNIP1) mRNA. The diagnostic value of miR-138-5p was analyzed using receiver operating characteristic (ROC) curve analysis, sensitivity, and specificity. We explored the effect of miR-138-5p on cell proliferation and metastasis by CCK-8, colony formation, wound healing and transwell assays. Western blot was employed to detect the protein expression of SNIP1 and related genes. Lung cancer cell growth was evaluated in vivo using xenograft tumor assay.

Results: MiR-138-5p was decreased in the serum of patients with non-small cell lung cancer (NSCLC) and in NSCLC cells and tissues. The area under the ROC curve of serum miR-138-5p in the diagnosis of NSCLC was 0.922. This finding indicates the high diagnostic efficiency for lung cancer. MiR-138-5p suppressed but its inhibitor promoted cell proliferation and migration compared with control treatment in vitro and in vivo. MiR-138-5p directly binds to the 3'-untranslated region of SNIP1 and negatively regulated the expression of SNIP1, thereby inhibiting the expression of cyclin D1 and c-Myc. Moreover, overexpression of SNIP1 rescues the miR-138-5p-mediated inhibition in NSCLC cells.

Conclusions: The results suggested that miR-138-5p suppressed lung cancer cell proliferation and migration by targeting SNIP1. Serum miR-138-5p is a novel and valuable biomarker for NSCLC diagnosis.

Keywords: SNIP1; biomarker; lung cancer; miR-138-5p; tumor suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / pathology
  • MicroRNAs* / genetics
  • RNA-Binding Proteins / genetics

Substances

  • MicroRNAs
  • SNIP1 protein, human
  • RNA-Binding Proteins
  • MIRN138 microRNA, human