LncRNA NEAT1 promotes the tumorigenesis of colorectal cancer by sponging miR-193a-3p

Cell Prolif. 2019 Jan;52(1):e12526. doi: 10.1111/cpr.12526. Epub 2018 Nov 8.

Abstract

Objectives: LncRNA nuclear-enriched abundant transcript 1 (NEAT1) participates in the development and progression of multiple malignancies. However, the molecular mechanism by which NEAT1 contributes to colorectal cancer (CRC) remains unclear.

Methods: The association between lncRNA NEAT1 expression and clinicopathological characteristics and prognosis in patients with CRC was analysed by TCGA RNA-sequencing data. MTT, colony formation, flow cytometry, transwell assays and a xenograft tumour model were used to assess the functions of NEAT1. Bioinformatics and spearman correlation analysis were used to identify the NEAT1-specific binding with miRNAs, and luciferase gene report and RIP assays were performed to confirm the interaction between miR-193a-3p (miR-193a) and NEAT1 in CRC cells.

Results: Upregulation of NEAT1 expression was significantly correlated with TNM stage, poor survival and tumour recurrence in patients with CRC, and acted as an independent prognostic factor for tumour recurrence. Knockdown of NEAT1 suppressed cell proliferation, colony formation abilities and invasive potential and induced cell apoptosis, but overexpression of NEAT1 reversed these effects. Furthermore, NEAT1 was confirmed to act as a sponge of miR-193a, and knockdown of NEAT1 attenuated miR-193a inhibitor-induced tumour promoting effects and L17RD expression in CRC cells. miR-193a harboured negative correlation with NEAT1 and IL17RD expression in CRC specimens. In vivo experiment further validated the inhibitory effects of NEAT1 knockdown on xenograft tumour growth.

Conclusion: Our findings demonstrate that lncRNA NEAT1 acts as an oncogenic role in CRC cells by sponging miR-193a and may represent a potential marker for CRC patients.

Keywords: LncRNA NEAT1; colorectal cancer; growth; miR-193a-3p.

MeSH terms

  • Aged
  • Animals
  • Apoptosis / genetics
  • Caco-2 Cells
  • Cadherins / biosynthesis
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • RNA, Long Noncoding / genetics*
  • Up-Regulation
  • Vimentin / biosynthesis
  • Xenograft Model Antitumor Assays

Substances

  • Cadherins
  • MIRN193 microRNA, human
  • MicroRNAs
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • Vimentin