Department of Hematology, Anhui No. 2 Provincial People's Hospital, Hefei, Anhui 230041, P.R. China.
Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
Mol Med Rep. 2021 Sep;24(3). doi: 10.3892/mmr.2021.12288. Epub 2021 Jul 19.
Multiple myeloma (MM) is a malignancy of plasma cells that leads to marrow failure and bone lesions. Numerous studies have verified the link between long non‑coding RNAs (lncRNAs) and MM. The present study aimed to examine the role and underlying mechanism of differentiation antagonizing non‑protein coding RNA (DANCR) in MM cells. The relative expression levels of DANCR, microRNA (miR)‑135b‑5p and Krüppel‑like factor 9 (KLF9) were examined using reverse transcription‑quantitative PCR. Cell viability was assessed using the MTT assay, while relative cell migration and invasion were evaluated using Transwell assays. Moreover, the dual‑luciferase reporter assay was used to examine the interplay between DANCR, miR‑135b‑5p and KLF9. Western blotting was performed to determine the expression level of KLF9. It was found that lncRNA DANCR and KLF9 were downregulated, while miR‑135b‑5p was upregulated in the serum of patients with MM and in MM cells compared with the controls. Overexpressing DANCR or knocking down miR‑135b‑5p reduced the viability of the MM cells, as well as restrained MM cells from migrating and invading. Furthermore, DANCR directly targeted miR‑135b‑5p and was negatively correlated with miR‑135b‑5p. It was also found that KLF9 was targeted by miR‑135b‑5p and was inversely correlated with miR‑135b‑5p expression. The impact of lncRNA DANCR‑mediated suppression on cell viability, invasion and migration was partially abolished by short hairpin RNA KLF9 or miR‑135b‑5p mimics transfection in MM cells. Thus, it was suggested that lncRNA DANCR repressed the viability, migration and invasion of MM cells by sponging miR‑135b‑5p to target KLF9.
多发性骨髓瘤（MM）是一种浆细胞恶性肿瘤，可导致骨髓衰竭和骨病变。大量研究已经证实了长非编码 RNA（lncRNA）与 MM 之间的联系。本研究旨在探讨分化拮抗非编码 RNA（DANCR）在 MM 细胞中的作用及其潜在机制。采用逆转录定量 PCR 检测 DANCR、microRNA（miR）-135b-5p 和 Krüppel 样因子 9（KLF9）的相对表达水平。采用 MTT 法检测细胞活力，Transwell 法检测细胞相对迁移和侵袭能力。此外，采用双荧光素酶报告基因实验检测 DANCR、miR-135b-5p 和 KLF9 之间的相互作用。采用 Western blot 法检测 KLF9 的表达水平。结果发现，与对照组相比，MM 患者血清和 MM 细胞中 lncRNA DANCR 和 KLF9 下调，而 miR-135b-5p 上调。过表达 DANCR 或敲低 miR-135b-5p 可降低 MM 细胞活力，并抑制 MM 细胞迁移和侵袭。此外，DANCR 可直接靶向 miR-135b-5p，且与 miR-135b-5p 呈负相关。还发现，miR-135b-5p 可靶向 KLF9，且与 miR-135b-5p 表达呈负相关。在 MM 细胞中，短发夹 RNA KLF9 或 miR-135b-5p 模拟物转染部分消除了 lncRNA DANCR 介导的抑制对细胞活力、侵袭和迁移的影响。因此，lncRNA DANCR 通过海绵吸附 miR-135b-5p 靶向 KLF9 抑制 MM 细胞活力、迁移和侵袭。
