Autophagy regulation by microRNAs: Novel insights into osteosarcoma therapy

IUBMB Life. 2020 Jul;72(7):1306-1321. doi: 10.1002/iub.2277. Epub 2020 Mar 31.

Abstract

Osteosarcoma (OS) is a kind of primary bone cancer that is considered as the leading cause of children death. Surgery and chemotherapy are considered as common treatment approaches for OS; the rate of survival for patients is almost 60-70%. Besides the used therapeutic approaches, it seems that there is a crucial need to launch new treatments for OS. In this regard, more understanding about cellular and molecular pathways involved in OS can contribute to recovery and develop new therapeutic platforms. Autophagy is a cellular machinery that digests and degrades dysfunctional proteins and organelles, so it can regulate the cell proliferation and survival. Most of the time, OS cells use autophagy to increase their survival and proliferation and to gain the ability to resist chemotherapy. Although, there are several controversial evidences on how OS cells use autophagy. A variety of cellular and molecular pathways, that is, microRNAs (miRNAs) can modulate autophagy. MiRNAs are some endogenous, approximately 22 nucleotide RNAs that have an important role in posttranscriptional regulation of mRNAs by targeting them. There are many evidences that the various miRNA expressions in OS cells are dysregulated, so it can propel a normal cell to cancerous one by influencing the cell survival, apoptosis, and autophagy, and eventually increased chemoresitance. Hence, miRNAs can be considered as new biomarkers for OS diagnosis, and according to the role of autophagy in OS progression, miRNAs can use inhibiting or promoting autophagy agents. The present review summarizes the effects of aberrant expression of miRNAs in OS diagnosis and treatment with focus on their roles in autophagy.

Keywords: autophagy; microRNA; osteosarcoma.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Autophagy*
  • Autophagy-Related Proteins / antagonists & inhibitors*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • MicroRNAs / genetics*
  • Molecular Targeted Therapy
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology

Substances

  • Antineoplastic Agents
  • Autophagy-Related Proteins
  • MicroRNAs