LncRNA TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the miR-134-5p/MBTD1 axis

Aging (Albany NY). 2019 Oct 10;11(19):8374-8385. doi: 10.18632/aging.102325. Epub 2019 Oct 10.

Abstract

Aim: To explore the mechanism by which long non-coding RNA (lncRNA) TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the microRNA miR-134-5p/malignant brain tumour domain containing 1 (MBTD1) axis.

Results: The lncRNA TTN-AS1 was highly expressed in osteosarcoma and was associated with poor prognosis. The lncRNA TTN-AS1 promoted cell viability and inhibited apoptosis. MiR-134-5p targeted MBTD1, which was regulated by lncRNA TTN-AS1. MBTD1 was highly expressed in osteosarcoma and was associated with poor prognosis. MBTD1 promoted cell viability and inhibited apoptosis, and knockdown of MBTD1 reversed the cancer-promoting effects of lncRNA TTN-AS1. Downregulation of lncRNA TTN-AS1 reduced drug resistance.

Conclusion: In osteosarcoma, lncRNA TTN-AS1 promoted the expression of MBTD1 by targeting miR-134-5p and regulated cell growth, apoptosis and drug resistance.

Methods: The expression characteristics of genes in osteosarcoma patients were analysed using bioinformatics. Plasmid transfection technology was applied to silence or overexpress lncRNA TTN-AS1, miR-134-5p and MBTD1. Western blotting and quantitative polymerase chain reaction (qPCR) were used to detect protein and RNA, respectively. A cell counting kit 8 (CCK-8) and flow cytometry were used to detect cell viability and apoptosis. The effects of lncRNA TTN-AS1 and MBTD1 on osteosarcoma in vivo were studied by using a tumour burden assay.

Keywords: aging and age-related diseases; lncRNA TTN-AS1; malignant brain tumour domain containing protein 1; miR-134-5p; osteosarcoma; resistance.

MeSH terms

  • Aging / physiology*
  • Apoptosis* / drug effects
  • Apoptosis* / genetics
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Chromosomal Proteins, Non-Histone / genetics*
  • Computational Biology
  • Drug Resistance / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • Osteosarcoma* / genetics
  • Osteosarcoma* / metabolism
  • RNA, Long Noncoding / genetics*

Substances

  • Chromosomal Proteins, Non-Histone
  • MBTD1 protein, human
  • MIRN134 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding