Cinnamtannin B-1 Inhibits the Progression of Osteosarcoma by Regulating the miR-1281/PPIF Axis

Biol Pharm Bull. 2023 Jan 1;46(1):67-73. doi: 10.1248/bpb.b22-00600. Epub 2022 Oct 22.

Abstract

Osteosarcoma (OS), one of the bone tumors, occurs mainly during childhood and adolescence and has an incidence rate of 5%. Cinnamtannin B-1 (CTB-1) is a natural trimeric proanthocyanidin compound found in plants Cinnamomum zeylanicum and Laurus nobilis. Previously, several articles have demonstrated that CTB-1 exerts a certain effect on melanoma and cervical cancer. However, their role in OS remains unclear. In this study, CTB-1 was found to inhibit the proliferation of OS cancer cells, with the dose of CTB-1 positively correlated to the survival rate of HOS and MG-63 cells. Recently, microRNAs (miRNAs) were also reported to play an important role in tumor proliferation. Hence, we performed the miRNA sequencing analysis after CTB-1 treatment to identify miRNA levels in HOS cells and found that the expression of miR-1281 was significantly upregulated. According to the functional analysis, CTB-1 inhibited the growth and migration of OS by upregulating the expression of miR-1281. Additionally, miR-1281 acted as a sponge for Peptidylprolyl Isomerase F (PPIF), inhibiting its expression levels. The rescue experiments revealed that CTB-1 delayed the development of OS by regulating the miR-1281/PPIF pathway. Hence, our findings suggested that CTB-1 inhibited the cell growth, invasion, and migration of OS by upregulating miR-1281 and inhibiting PPIF expression, thereby providing a possible target drug for OS treatment.

Keywords: cinnamtannin B-1; miR-1281; osteosarcoma; proliferation.

MeSH terms

  • Apoptosis
  • Bone Neoplasms* / drug therapy
  • Bone Neoplasms* / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cyclophilins* / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • Osteosarcoma* / drug therapy
  • Osteosarcoma* / genetics
  • Proanthocyanidins* / pharmacology

Substances

  • cinnamtannin B-1
  • MicroRNAs
  • MIRN1281 microRNA, human
  • Proanthocyanidins
  • PPID protein, human
  • Cyclophilins