Long non-coding RNA CCAT1 promotes multiple myeloma progression by acting as a molecular sponge of miR-181a-5p to modulate HOXA1 expression

Cell Cycle. 2018;17(3):319-329. doi: 10.1080/15384101.2017.1407893. Epub 2018 Jan 29.

Abstract

Multiple myeloma (MM) is the second most common hematological cancer all over the world. Long non-coding RNA (lncRNA) colon cancer associated transcript-1 (CCAT1) has been reported to play important roles in the development and progression of multiple human malignancies. However, little is known about its functional role and molecular mechanism in MM. The aim of this study was to investigate the clinical and biological significance of CCAT1 in MM. Our data showed that the relative expression levels of CCAT1 were significantly upregulated in MM tissues and cell lines compared with healthy donors and normal plasma cells (nPCs). High expression of CCAT1 was correlated shorter overall survival of MM patients. CCAT1 knockdown significantly inhibited cell proliferation, induced cell cycle arrest at G0/G1 phase and promoted cell apoptosis in vitro, and suppressed tumor growth in vivo. MiR-181a-5p was a direct target of CCAT1, and repression of miR-181a-5p could rescue the inhibition of CCAT1 knockdown on MM progression. In addition, CCAT1 positively regulated HOXA1 expression through sponging miR-181a-5p in MM cells.taken together, lncRNA CCAT1 exerted an oncogenic role in MM by acting as a ceRNA of miR-181a-5p. These results suggest that CCAT1 may serve as a novel diagnostic marker and therapeutic target for MM.

Keywords: CCAT1; HOXA1; LncRNA; miR-181a-5p; multiple myeloma.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Base Sequence
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / metabolism*
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / pathology*
  • Prognosis
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Transcription Factors / metabolism*
  • Up-Regulation

Substances

  • CCAT1 long noncoding RNA, human
  • Homeodomain Proteins
  • MIrn181 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Transcription Factors
  • homeobox A1 protein