LncRNA FAL1 is a negative prognostic biomarker and exhibits pro-oncogenic function in osteosarcoma

J Cell Biochem. 2018 Nov;119(10):8481-8489. doi: 10.1002/jcb.27074. Epub 2018 Jul 10.

Abstract

Long noncoding RNA focally amplified lncRNA on chromosome 1 (FAL1) plays an important role in the development of several human malignancy entities. However, the expression and function of FAL1 in the carcinogenesis and development of osteosarcoma remain unknown. In this study, we detected the FAL1 levels in human osteosarcoma tissues and cell lines by quantitative real-time polymerase chain reaction and investigated its role in osteosarcoma using in vitro assays. Our results showed that FAL1 expression was significantly upregulated in human osteosarcoma tissues and cell lines compared with their normal controls. FAL1 expression level was positively correlated with the distance metastasis (P = .008) and tumor stage ( P = .013). Higher expression of FAL1 conferred a significantly poorer survival, as determined by the Kaplan-Meier method with the log-rank test. Multivariate Cox proportional hazards analysis revealed that FAL1 was probably an independent risk of overall survival. Additionally, the serum FAL1 expression level was associated with osteosarcoma status in patients. Receiver operating characteristic curve analysis demonstrated that FAL1 expression was different between patients with osteosarcoma and healthy cohorts (area under the curve, 0.839; P < .001). Furthermore, knockdown of FAL1 by small interfering RNA significantly inhibited cell proliferation via inducing G2/M arrest in osteosarcoma cells. Depletion of FAL1 also suppressed osteosarcoma cell migration and invasion, which might be mediated by inhibiting the epithelial-mesenchymal transition (EMT) program. Taken together, our study showed that lncRNA FAL1 exhibits an important pro-oncogenic effect on osteosarcoma progression by targeting EMT, which may serve as a potential therapeutic target for osteosarcoma.

Keywords: focally amplified long noncoding RNA on chromosome 1; long noncoding RNA; osteosarcoma; prognostic biomarker; signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Bone Neoplasms / blood*
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Knockdown Techniques
  • Gene Silencing
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Osteosarcoma / blood*
  • Osteosarcoma / genetics*
  • Osteosarcoma / mortality
  • Osteosarcoma / pathology
  • Prognosis
  • Proportional Hazards Models
  • RNA, Long Noncoding / blood*
  • RNA, Long Noncoding / genetics*
  • Survival Rate
  • Transfection
  • Up-Regulation / genetics

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • focally amplified long noncoding RNA on chromosome 1, human