LncRNA HCG18 Promotes Osteosarcoma Cells Proliferation, Migration, and Invasion in by Regulating miR-34a/RUNX2 Pathway

Biochem Genet. 2023 Jun;61(3):1035-1049. doi: 10.1007/s10528-022-10294-5. Epub 2022 Nov 19.

Abstract

Osteosarcoma (OS) is a type of tumor with high malignant behaviors. Increasing investigates have confirmed that long non-coding RNA HLA complex group 18 (lncRNA HCG18) acted as a tumor-promoting factor in multiple tumors. Nevertheless, the underlying mechanism of HCG18 on OS remains largely unclear. HCG18, miR-34a, and runt-related transcription factor 2 (RUNX2) expressions were detected by quantitative real-time PCR (RT-qPCR) or western blotting assays, respectively. The underlying tumorigenic phenotypes were detected by MTT, wound healing, transwell invasion, western blotting assays. Molecular interactions were verified by dual-luciferase report assay. HCG18 and RUNX2 were notably enhanced, whereas miR-34a was decreased in OS tumor tissues and cell lines. Functional experiments uncovered that HCG18 silencing significantly inhibited the capabilities of proliferation, migration, and invasion, while overexpression of HCG18 play the opposite roles. Furthermore, HCG18 directly bound to miR-34a, and miR-34a was confirm to be a negative regulator of RUNX2. Interestingly, the anti-tumor effects of HCG18 silencing were attenuated by miR-34a inhibitor and RUNX2 overexpression. Taken together, the present study suggested that HCG18 promoted the malignant biological behaviors of OS through regulating the miR-34a/RUNX2 pathway, implying HCG18 might serve as a new target for OS treatment.

Keywords: Invasion; Osteosarcoma; RUNX2; lncRNA HCG18; miR-34a.

MeSH terms

  • Bone Neoplasms* / genetics
  • Bone Neoplasms* / metabolism
  • Bone Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / physiology
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Osteosarcoma* / genetics
  • Osteosarcoma* / metabolism
  • Osteosarcoma* / pathology
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • Core Binding Factor Alpha 1 Subunit
  • RUNX2 protein, human