The regulation of CD47-SIRPα signaling axis by microRNAs in combination with conventional cytotoxic drugs together with the help of nano-delivery: a choice for therapy?

Mol Biol Rep. 2021 Jul;48(7):5707-5722. doi: 10.1007/s11033-021-06547-y. Epub 2021 Jul 17.

Abstract

CD47, a member of the immunoglobulin superfamily, is an important "Don't Eat-Me" signal in phagocytosis process [clearance of apoptotic cells] as well as a regulator of the adaptive immune response. The lower level of CD47 on the cell surface leads to the clearance of apoptotic cells. Dysregulation of CD47 plays a critical role in the development of disorders, particularly cancers. In cancers, recognition of CD47 overexpression on the surface of cancer cells by its receptor, SIRPα on the phagocytic cells, inhibits phagocytosis of cancer cells. Thus, blocking of CD47-SIRPα signaling axis might be as a promising therapeutic target, which promotes phagocytosis of cancer cells, antigen-presenting cell function as well as adaptive T cell-mediated anti-cancer immunity. In this respect, it has been reported that CD47 expression can be regulated by microRNAs (miRNAs). MiRNAs can regulate phagocytosis of macrophages apoptotic process, drug resistance, relapse of disease, radio-sensitivity, and suppress cell proliferation, migration, and invasion through post-transcriptional regulation of CD47-SIRPα signaling axis. Moreover, the regulation of CD47 expression by miRNAs and combination with conventional cytotoxic drugs together with the help of nano-delivery represent a valuable opportunity for effective cancer treatment. In this review, we review studies that evaluate the role of miRNAs in the regulation of CD47-SIRPα in disorders to achieve a novel preventive, diagnostic, and therapeutic strategy.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Also, kindly confirm the details in the metadata are correct. Confirmed.Journal standard instruction requires a structured abstract; however, none was provided. Please supply an Abstract with subsections..Not confirmed. This is a review article. According to submission guidelines: "The abstract should be presented divided into subheadings (unless it is a mini or full review article)". Kindly check and confirm whether the corresponding authors and mail ID are correctly identified. Confirmed.

Keywords: CD47; Immunotherapy; Nano-strategies; RNAi; SIRPα; miRNA.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • CD47 Antigen / genetics
  • CD47 Antigen / metabolism*
  • Disease Management
  • Disease Susceptibility
  • Drug Carriers / chemistry
  • Drug Delivery Systems
  • Gene Expression Regulation / drug effects*
  • Humans
  • MicroRNAs / genetics*
  • Nanoparticles / chemistry
  • Neoplasms / drug therapy
  • Neoplasms / etiology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Organ Specificity
  • Phagocytosis / drug effects
  • RNA Interference*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Signal Transduction / drug effects*

Substances

  • Antigens, Differentiation
  • Antineoplastic Agents
  • CD47 Antigen
  • CD47 protein, human
  • Drug Carriers
  • MicroRNAs
  • Receptors, Immunologic
  • SIRPA protein, human