Shikonin induces cell autophagy via modulating the microRNA -545-3p/guanine nucleotide binding protein beta polypeptide 1 axis, thereby disrupting cellular carcinogenesis in colon cancer

Bioengineered. 2022 Mar;13(3):5928-5941. doi: 10.1080/21655979.2021.2024638.

Abstract

Shikonin (SHK), a major component of shiverweed, was provided with anti-tumor effects via multiple targets and signal pathways. Nevertheless, the specific mechanism of its function in colorectal cancer (CRC) still needed to be further explored. The study was designed to examine the role of SHK in CRC and its specific mechanism on the cell tumor behavior of CRC. Collection of clinical samples was performed, and test of microRNA (miR)-545-3p and guanine nucleotide-binding protein beta polypeptide 1 (GNB1) in the samples was conducted; Selection of CRC cell line was exerted, and examination of miR-545-3p and GNB1 was performed; After treatment of shikonin (SHK), correlated plasmids were transfected, test of cell advancement was performed. Test of the protein of autophagy-correlated proteins light chain 3-II/light chain 3I and p63 was performed. The interaction of miR-545-3p with GNB1 was explored, and the action of SHK in vivo was tested. SHK repressed the advancement of SW480 cells with elevated apoptosis and autophagy and the cells quantities in G0/G1 phase. MiR-545-3p was elevated in CRC. SHK boosted miR-545-3p, repression of miR-545-3p or augmentation of GNB1 was able to turn around the function of SHK on CRC, and GNB1 was the target gene of miR-545-3p.All in all, SHK stimulates apoptosis and autophagy in CRC via miR-545-3p/GNB1 signaling axis, firstly demonstrating the regulatory mechanism of SHK in CRC via miR-545-3p/GNB1 axis.

Keywords: Shikonin; autophagy; colorectal cancer; guanine nucleotide binding protein beta polypeptide 1; microrna-545-3p.

MeSH terms

  • Autophagy / genetics
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colonic Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • GTP-Binding Protein beta Subunits* / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • Naphthoquinones

Substances

  • GNB1 protein, human
  • GTP-Binding Protein beta Subunits
  • MIR545 microRNA, human
  • MicroRNAs
  • Naphthoquinones
  • shikonin

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.