lncRNA TUSC7 inhibits osteosarcoma progression through the miR‑181a/RASSF6 axis

Int J Mol Med. 2021 Feb;47(2):583-594. doi: 10.3892/ijmm.2020.4825. Epub 2020 Dec 18.


Osteosarcoma (OS) is one of the most aggressive malignancies, accompanied by an elevated incidence and a decreased rate of healing. Recently, several long non‑coding RNAs (lncRNAs) have been reported to be involved in OS progression. Although tumor suppressor candidate 7 (TUSC7) was reported as a novel lncRNA, little is known about its biological functions in OS. The present study was designed to explore whether TUSC7 was involved in the pathological development of OS using various methods, including hematoxylin and eosin staining, Cell Counting Kit‑8 assay, colony formation assay and Transwell assay. The present study revealed that TUSC7 expression was downregulated in OS tissues and cell lines compared with in normal tissues and cell lines. Functionally, the current results revealed that overexpression of TUSC7 inhibited OS cell proliferation, migration and invasion, while promoting apoptosis in vitro and in vivo. Next, the subcellular distribution of TUSC7 was examined by nuclear/cytoplasmic RNA fractionation and reverse transcription‑quantitative PCR. Mechanistic studies revealed that TUSC7 exerted its role by sponging microRNA (miR)‑181a in OS cell lines. Ras association domain family member 6 (RASSF6) was confirmed as a target gene of miR‑181a, and the expression levels of RASSF6 were negatively regulated by miR‑181a. Additionally, the results of rescue experiments suggested that overexpression of miR‑181a neutralized the inhibitory effects of TUSC7 overexpression on OS cells. Overall, the present study demonstrated that the tumor suppressor role of TUSC7 in OS progression was mediated through the miR‑181a/RASSF6 axis, which may represent a new therapeutic target for OS.

Keywords: osteosarcoma; long non-coding RNA tumor suppressor candidate 7; microRNA-181a; Ras association domain family member 6.

MeSH terms

  • Adolescent
  • Adult
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Child
  • Female
  • Genes, Tumor Suppressor*
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • Signal Transduction*


  • Apoptosis Regulatory Proteins
  • MIrn181 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RASSF6 protein, human
  • RNA, Long Noncoding
  • RNA, Neoplasm
  • loc285194 LncRNA, human