lncRNA TUG1 promotes the development of oral squamous cell carcinoma by regulating the MAPK signaling pathway by sponging miR-593-3p

Cell Cycle. 2022 Sep;21(17):1856-1866. doi: 10.1080/15384101.2022.2074624. Epub 2022 May 23.

Abstract

Dysregulation of non-coding RNAs (ncRNAs) has been proved to play important roles in oral squamous cell carcinoma (OSCC). This study aimed to determine the combined role of lncRNA TUG1, miR-593-3p, and MAPK signaling in oral squamous cell carcinoma (OSCC) development. Here, we found that TUG1 was up-regulated in OSCC tissues and cell lines. Silencing TUG1 suppressed proliferation migration, invasion and promoted apoptosis of OSCC cells. We also validated that knockdown of TUG1 suppressed MAPK signaling pathway and inhibited EMT process in OSCC cells. Then, a novel LncRNA TUG1/ miR-593-3p/MAPK axis was verified to rescue cell viability in OSCC cells. Mechanistically, miR-593-3p bound to lncRNA TUG1, and lncRNA TUG1 positively regulated MAPK related proteins through acting as RNA sponger for miR-593-3p. Further gain- and loss-of-function experiments evidenced that the protective effects of lncRNA TUG1 knock-down on OSCC cells were abrogated by silencing miRNA-593-3p. The OSCC nude mice model experiments demonstrated that depletion of TUG1 further inhibited tumor growth. In conclusion, appropriate diagnostic biomarkers and therapies for OSCC can be identified by targeting the TUG1/miR-593-3p/MAPK axis.

Keywords: MAPK; Oral squamous cell carcinomas; lncRNA TUG1; miR-593-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • Mouth Neoplasms* / genetics
  • Mouth Neoplasms* / pathology
  • RNA, Long Noncoding* / genetics
  • Signal Transduction
  • Squamous Cell Carcinoma of Head and Neck* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / pathology

Substances

  • MIRN593 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TUG1 long noncoding RNA, human

Grants and funding

This work was supported by Project of Wuhan University (No.2042022kf1214).