MicroRNA-363-3p downregulation in papillary thyroid cancer inhibits tumor progression by targeting NOB1

J Investig Med. 2021 Jan;69(1):66-74. doi: 10.1136/jim-2020-001562. Epub 2020 Oct 19.

Abstract

MicroRNA-363-3 p (miR-363-3 p) has been reported to play a crucial role in tumor development and progression, and function as a tumor suppressor in many types of cancer. In our previous studies, we found that miRNA-363-3 p inhibited papillary thyroid carcinoma (PTC) progression by targeting PIK3CA. Meanwhile, we found that NIN1/RPN12 binding protein 1 (NOB1) was significantly upregulated in thyroid carcinoma tissue and downregulation of NOB1 expression significantly inhibited cell proliferation, migration and invasion in PTC. However, the correlation of NOB1 and miR-363-3 p has not been investigated. Here, we performed bioinformatic analysis to explore miRNA targeting NOB1. We found that NOB1 was a target of miR-363-3 p and miR-363-3 p regulated NOB1 expression at the translational and transcriptional levels by targeting its 3' untranslated region (3'-UTR). Further, we showed that miR-363-3 p inhibited tumor progression by targeting NOB1 in vitro and in vivo. We found that overexpression miR-363-3 p or silencing NOB1 significantly increased G0/G1-phase and decreased S-phase in the human papillary thyroid cells, which led to a significant delay in cell proliferation, indicating miR-363-3 p and NOB1 are crucial for human papillary thyroid cancer tumorigenesis. Collectively, our data unveil that miR-363-3 p negatively regulates NOB1 activity by reducing its stability. This study provides a new therapeutic target for regulation of NOB1 stability to modulate human papillary thyroid cancer progression.

Keywords: RNA; cell proliferation; thyroid neoplasms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / genetics
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Heterografts
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Nuclear Proteins / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Thyroid Cancer, Papillary / genetics*
  • Thyroid Cancer, Papillary / pathology

Substances

  • 3' Untranslated Regions
  • MIRN363 microRNA, human
  • MicroRNAs
  • NOB1 protein, human
  • Nuclear Proteins
  • RNA-Binding Proteins