Genome‑wide profiling of lncRNA expression patterns in patients with acute promyelocytic leukemia with differentiation therapy

Oncol Rep. 2018 Sep;40(3):1601-1613. doi: 10.3892/or.2018.6521. Epub 2018 Jun 25.

Abstract

Long non‑coding RNAs (lncRNAs) are crucial factors in acute promyelocytic leukemia (APL) cell differentiation. However, their expression patterns and regulatory functions during all‑trans‑retinoic acid (ATRA)‑induced APL differentiation remain to be fully elucidated. The profile of dysregulated lncRNAs between three bone marrow (BM) samples from patients with APL post‑induction and three BM samples from untreated matched controls was examined with the Human Transcriptome Array 2.0. The dysregulated lncRNA expression of an additional 27 APL BM samples was validated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis. The lncRNA functions were predicted through co‑expressed messenger RNA (mRNA) annotations. Co‑expressed lncRNA‑mRNA networks were constructed to analyze the functional pathways. In total, 825 lncRNAs and 1,218 mRNAs were dysregulated in the treated APL BM group, compared with the untreated APL BM group. The expression of 10 selected lncRNAs was verified by RT‑qPCR analysis. During APL differentiation, NONHSAT076891 was the most upregulated lncRNA, whereas TCONS_00022632‑XLOC_010933 was the most downregulated. Functional analysis revealed that several lncRNAs may exert activities in biological pathways associated with ATRA‑induced APL differentiation through cis and/or trans regulation of mRNAs. The findings of the present study assist in explaining the contributions of lncRNAs in APL myeloid differentiation and improve current knowledge on the potential mechanisms regarding dysregulated lncRNA expression in ATRA‑induced APL differentiation.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / pharmacology
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics*
  • Computational Biology
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Gene Regulatory Networks
  • Genome, Human*
  • Humans
  • Leukemia, Promyelocytic, Acute / drug therapy
  • Leukemia, Promyelocytic, Acute / genetics*
  • Leukemia, Promyelocytic, Acute / pathology
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Transcriptome
  • Tretinoin / pharmacology*
  • Young Adult

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • Tretinoin