Downregulation of lncRNA UCA1 facilitates apoptosis and reduces proliferation in multiple myeloma via regulation of the miR-1271-5p/HGF axis

J Chin Med Assoc. 2019 Sep;82(9):699-709. doi: 10.1097/JCMA.0000000000000145.

Abstract

Background: Long noncoding RNAs (lncRNAs) are considered to be a novel prognostic and therapeutic target in many cancers. This study identified dysregulation of lncRNA urothelial carcinoma associated 1 (UCA1) and hepatocyte growth factor (HGF) mRNA via the Gene Expression Omnibus (GEO) database, which was traced to the mutual target miRNA, miR-1271-5p, and their effects were explored in multiple myeloma (MM).

Methods: RNA expression profiles of MM were downloaded from the GEO database and analyzed using R packages. The expression of RNAs in MM tissue samples and cells was evaluated through quantificational real-time polymerase chain reaction (qRT-PCR). A luciferase reporter assay was utilized to confirm the binding relationships between UCA1/HGF and miR-1271-5p. To assess cell proliferation and apoptosis, CCK-8 assays and flow cytometry were conducted. Additionally, tumor progression was demonstrated in vivo.

Results: LncRNA UCA1 and HGF expression was higher in the cells and samples of patients with MM than in normal plasma cells. miR-1271-5p was confirmed to be the target of lncRNA UCA1 and HGF and to be negatively correlated with them. Moreover, downregulation of lncRNA UCA1 and HGF inhibited cell proliferation and facilitated cell apoptosis in RPMI 8226 cells (human MM cell line). However, miR-1271-5p overexpression affected the proliferation decrease and apoptosis increase. Moreover, in vivo experiments indicated that down or upregulation of lncRNA UCA1 repressed or enhanced the tumor growth of MM, respectively, in xenograft models.

Conclusion: LncRNA UCA1 promoted proliferation and inhibited apoptosis by regulating miR-1271-5p and HGF in the human MM cell line RPMI 8226. Our investigations might contribute to a better understanding of the lncRNA UCA1/miR-1271-5p/HGF axis as a potential therapeutic strategy in MM.

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Hepatocyte Growth Factor / physiology*
  • Humans
  • Mice
  • MicroRNAs / physiology*
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / pathology*
  • RNA, Long Noncoding / physiology*

Substances

  • HGF protein, human
  • MIRN1271 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • UCA1 RNA, human
  • Hepatocyte Growth Factor