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Hint1 Overexpression Inhibits the Cell Cycle and Induces Cell Apoptosis in Human Osteosarcoma Cells

Dong-Dong Duan1, Hui Xie1, Hua-Feng Shi1

  • 1Department of Orthopedic Surgery, The First People's Hospital of Jingmen, Jingmen, Hubei 448000, People's Republic of China.

Oncotargets and Therapy
|September 5, 2020
PubMed
Abstract

Insights

Histidine triad nucleotide-binding protein 1 (Hint1) suppresses osteosarcoma (OS) development by inhibiting proliferation and promoting apoptosis. Hint1 downregulates cyclin D1 via FOXO1, suggesting its potential as an OS therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Histidine triad nucleotide-binding protein 1 (Hint1) demonstrates tumor suppressor activity in colorectal and gastric cancers.
  • The role of Hint1 in osteosarcoma (OS) development remains unexplored.

Purpose of the Study:

  • To investigate the function of Hint1 in human osteosarcoma cells.
  • To elucidate the molecular mechanisms underlying Hint1's role in OS.

Main Methods:

  • Utilized human OS cell lines (143B, U2OS, KHOS-240S, Saos-2, MG-63).
  • Assessed cell proliferation, cell cycle, and apoptosis using flow cytometry.
  • Employed adenovirus transfection for Hint1 and FOXO1 overexpression.

Main Results:

  • Hint1 expression was found to be downregulated in OS cell lines.
  • Overexpression of Hint1 inhibited proliferation and cell cycle progression while increasing apoptosis.
  • Hint1 suppressed cyclin D1 expression by inhibiting FOXO1; FOXO1 overexpression counteracted Hint1's effects.

Conclusions:

  • Hint1 acts as a tumor suppressor in osteosarcoma by regulating the FOXO1-cyclin D1 pathway.
  • Hint1 represents a potential therapeutic target for osteosarcoma treatment.
Keywords:
FOXO1apoptosiscell cyclehistidine triad nucleotide-binding protein 1osteosarcoma

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