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ZBTB7A, a miR-663a target gene, protects osteosarcoma from endoplasmic reticulum stress-induced apoptosis by

Lu Zhang1, Yuan Wang1, Li Zhang2

  • 1The Second Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, 116044, PR China.

Cancer Letters
|February 13, 2019
PubMed

Insights

ZBTB7A is a key survival factor in osteosarcoma cells experiencing endoplasmic reticulum (ER) stress. ER stress downregulates ZBTB7A, promoting cancer cell death and metastasis, highlighting a critical pathway for cell survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The role of ZBTB7A in tumorigenesis is established, but its function in endoplasmic reticulum (ER) stress responses is unclear.
  • Osteosarcoma is a significant bone cancer with complex regulatory mechanisms.
  • Understanding ER stress pathways is crucial for developing targeted cancer therapies.

Purpose of the Study:

  • To investigate the role of ZBTB7A in osteosarcoma cell survival under ER stress.
  • To elucidate the molecular mechanisms linking ER stress, ZBTB7A, and apoptosis in osteosarcoma.
  • To identify potential therapeutic targets within the identified signaling pathway.

Main Methods:

  • Utilized pharmacological inducers of ER stress (tunicamycin, thapsigargin) in osteosarcoma cell lines.
  • Assessed cell apoptosis in vitro and in vivo following ZBTB7A manipulation.
  • Performed mechanistic studies involving microRNA (miR-663a) and long non-coding RNA (LncRNA GAS5) interactions.
  • Analyzed ZBTB7A expression in human osteosarcoma tissues.

Main Results:

  • ZBTB7A acts as a prosurvival factor in osteosarcoma cells subjected to ER stress.
  • ER stress-induced downregulation of ZBTB7A promotes osteosarcoma cell apoptosis.
  • Elevated ZBTB7A expression correlates with osteosarcoma metastasis.
  • miR-663a directly targets ZBTB7A, contributing to its downregulation under ER stress.
  • ZBTB7A suppresses LncRNA GAS5, which is involved in ER stress-induced apoptosis.

Conclusions:

  • ZBTB7A plays a critical prosurvival role in osteosarcoma cells adapting to ER stress.
  • The miR-663a-ZBTB7A-LncRNA GAS5 axis is essential for osteosarcoma cell survival under ER stress.
  • Targeting this pathway could offer novel therapeutic strategies for osteosarcoma.
Keywords:
ER stressGAS5OsteosarcomaZBTB7AmiR-663a

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