Dysregulation of TCONS_00006091 contributes to the elevated risk of oral squamous cell carcinoma by upregulating SNAI1, IRS and HMGA2

Sci Rep. 2024 Apr 26;14(1):9616. doi: 10.1038/s41598-024-60310-4.

Abstract

In this study, we aimed to study the role of TCONS_00006091 in the pathogenesis of oral squamous cellular carcinoma (OSCC) transformed from oral lichen planus (OLP). This study recruited 108 OSCC patients which transformed from OLP as the OSCC group and 102 OLP patients with no sign of OSCC as the Control group. ROC curves were plotted to measure the diagnostic values of TCONS_00006091, miR-153, miR-370 and let-7g, and the changes in gene expressions were measured by RT-qPCR. Sequence analysis and luciferase assays were performed to analyze the molecular relationships among these genes. Cell proliferation and apoptosis were observed via MTT and FCM. TCONS_00006091 exhibited a better diagnosis value for OSCC transformed from OLP. OSCC group showed increased TCONS_00006091 expression and decreased expressions of miR-153, miR-370 and let-7g. The levels of SNAI1, IRS and HMGA2 was all significantly increased in OSCC patients. And TCONS_00006091 was found to sponge miR-153, miR-370 and let-7g, while these miRNAs were respectively found to targe SNAI1, IRS and HMGA2. The elevated TCONS_00006091 suppressed the expressions of miR-153, miR-370 and let-7g, leading to the increased expression of SNAI1, IRS and HMGA2. Also, promoted cell proliferation and suppressed apoptosis were observed upon the over-expression of TCONS_00006091. This study demonstrated that the expressions of miR-153, miR-370 and let-7g were down-regulated by the highly expressed TCONS_00006091 in OSCC patients, which accordingly up-regulated the expressions of SNAI1, IRS and HMGA2, resulting in the promoted cell proliferation and suppressed cell apoptosis.

Keywords: HMGA2; IRS; Oral squamous cellular carcinoma; Proliferation; SNAI1; lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis* / genetics
  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / metabolism
  • Carcinoma, Squamous Cell* / pathology
  • Cell Line, Tumor
  • Cell Proliferation* / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HMGA2 Protein* / genetics
  • HMGA2 Protein* / metabolism
  • Humans
  • Lichen Planus, Oral / genetics
  • Lichen Planus, Oral / metabolism
  • Lichen Planus, Oral / pathology
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Mouth Neoplasms* / genetics
  • Mouth Neoplasms* / metabolism
  • Mouth Neoplasms* / pathology
  • Snail Family Transcription Factors* / genetics
  • Snail Family Transcription Factors* / metabolism
  • Up-Regulation

Substances

  • Snail Family Transcription Factors
  • HMGA2 Protein
  • SNAI1 protein, human
  • MicroRNAs
  • HMGA2 protein, human