TSC complex decrease the expression of mTOR by regulated miR-199b-3p

Sci Rep. 2025 Jan 13;15(1):1892. doi: 10.1038/s41598-025-85706-8.

Abstract

The TSC complex formed by TSC1 and TSC2 is the most important upstream negative regulator of mTORC1. Genetic variations in either TSC1 or TSC2 cause tuberous sclerosis complex (TSC) disease which is a rare autosomal dominant disorder resulting in impairment of multiple organ systems. In this study, besides a reported variation, c.2509_2512del (p.Asn837Valfs*11, p.N837fs) in TSC1, we found a de novo TSC2 variation c.1113delG (p.Gln371Hisfs*18, p.Q371fs), which these two mutation influence the formation of TSC complex. We found that the decrease of TSC complex with the appearance of the decreased miR-199b-3p expression. At the same time, the reduction of miR-199b-3p increased the expression of mTOR and the activation of mTORC1 and mTORC2, the additional miR-199b-3p caused the decrease the expression of mTOR and the activation of mTORC1 and mTORC2. In brief, our results may illustrate a novel mechanism of TSC caused by variations in either TSC1 or TSC2, and a new mTOR expression regulator, miR-199b-3p.

Keywords: MTOR; MiR-199b-3p; TSC; TSC1; TSC2.

MeSH terms

  • Gene Expression Regulation
  • Humans
  • Mechanistic Target of Rapamycin Complex 1* / genetics
  • Mechanistic Target of Rapamycin Complex 1* / metabolism
  • Mechanistic Target of Rapamycin Complex 2 / genetics
  • Mechanistic Target of Rapamycin Complex 2 / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Mutation
  • TOR Serine-Threonine Kinases* / genetics
  • TOR Serine-Threonine Kinases* / metabolism
  • Tuberous Sclerosis / genetics
  • Tuberous Sclerosis / metabolism
  • Tuberous Sclerosis Complex 1 Protein* / genetics
  • Tuberous Sclerosis Complex 1 Protein* / metabolism
  • Tuberous Sclerosis Complex 2 Protein* / genetics
  • Tuberous Sclerosis Complex 2 Protein* / metabolism

Substances

  • MicroRNAs
  • Tuberous Sclerosis Complex 1 Protein
  • TOR Serine-Threonine Kinases
  • Tuberous Sclerosis Complex 2 Protein
  • mirn199 microRNA, human
  • TSC2 protein, human
  • TSC1 protein, human
  • Mechanistic Target of Rapamycin Complex 1
  • MTOR protein, human
  • Mechanistic Target of Rapamycin Complex 2