Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Research Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Oncol Rep. 2018 Sep;40(3):1601-1613. doi: 10.3892/or.2018.6521. Epub 2018 Jun 25.
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.
长链非编码 RNA（lncRNA）是急性早幼粒细胞白血病（APL）细胞分化的关键因素。然而，它们在全反式维甲酸（ATRA）诱导的 APL 分化过程中的表达模式和调节功能仍有待充分阐明。通过人类转录组阵列 2.0 检查了 3 例 APL 患者诱导后骨髓（BM）样本和 3 例未经治疗的匹配对照 BM 样本之间失调 lncRNA 的特征。通过逆转录-定量聚合酶链反应（RT-qPCR）分析验证了另外 27 例 APL BM 样本的失调 lncRNA 表达。通过共表达信使 RNA（mRNA）注释预测 lncRNA 功能。构建共表达 lncRNA-mRNA 网络以分析功能途径。与未经治疗的 APL BM 组相比，治疗的 APL BM 组中共有 825 个 lncRNA 和 1,218 个 mRNA 失调。通过 RT-qPCR 分析验证了 10 个选定 lncRNA 的表达。在 APL 分化过程中，NONHSAT076891 是上调最明显的 lncRNA，而 TCONS_00022632-XLOC_010933 是下调最明显的 lncRNA。功能分析表明，一些 lncRNA 可能通过 cis 和/或 trans 调节 mRNA 来发挥与 ATRA 诱导的 APL 分化相关的生物学途径中的活性。本研究的结果有助于解释 lncRNA 在 APL 髓样分化中的作用，并提高关于 ATRA 诱导的 APL 分化中失调 lncRNA 表达的潜在机制的现有知识。
