Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 452000, China.
Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 452000, China.
Exp Cell Res. 2020 Nov 1;396(1):112280. doi: 10.1016/j.yexcr.2020.112280. Epub 2020 Sep 19.
Long non-coding RNA (lncRNA) ANRIL has been reported to be closely related to the relapse of multiple myeloma patients. However, the functional role and underlying mechanism of lncRNA ANRIL in multiple myeloma are not known. This study aims to investigate the biological function of lncRNA ANRIL in multiple myeloma. In this study, compared with normal tissues from healthy donors, lncRNA ANRIL and HIF-1α expressions were up-regulated in tumor tissues from multiple myeloma patients. miR-411-3p expression was down-regulated in tumor tissues from multiple myeloma patients. Besides, lncRNA ANRIL can interact with miR-411-3p. HIF-1α was confirmed to be a target of miR-411-3p. Correlation analysis showed that lncRNA ANRIL expression was negatively correlated with miR-411-3p expression. HIF-1α expression was negatively correlated with miR-411-3p expression. Further transfection experiments showed that knockdown of ANRIL or overexpression of miR-411-3p significantly inhibited cell proliferation, tumor formation ability and tumor stem cell like property, promoted cell apoptosis in vitro. Finally, miR-411-3p mimic reduced tumor volume, improved survival rate, suppressed malignant proliferation and tumor stem cell like property in U266 xenograft model. Our results demonstrate that lncRNA ANRIL mediated by miR-411-3p promotes the malignant proliferation and tumor stem cell like property of multiple myeloma through regulating HIF-1α.
长链非编码 RNA（lncRNA）ANRIL 与多发性骨髓瘤患者的复发密切相关。然而，lncRNA ANRIL 在多发性骨髓瘤中的功能作用和潜在机制尚不清楚。本研究旨在探讨 lncRNA ANRIL 在多发性骨髓瘤中的生物学功能。在本研究中，与健康供体的正常组织相比，lncRNA ANRIL 和 HIF-1α 在多发性骨髓瘤患者的肿瘤组织中上调。miR-411-3p 在多发性骨髓瘤患者的肿瘤组织中下调。此外，lncRNA ANRIL 可以与 miR-411-3p 相互作用。HIF-1α 被证实是 miR-411-3p 的靶标。相关性分析表明，lncRNA ANRIL 表达与 miR-411-3p 表达呈负相关。HIF-1α 表达与 miR-411-3p 表达呈负相关。进一步的转染实验表明，敲低 ANRIL 或过表达 miR-411-3p 可显著抑制细胞增殖、肿瘤形成能力和肿瘤干细胞样特性，促进细胞凋亡。最后，miR-411-3p 模拟物降低了肿瘤体积，提高了存活率，抑制了 U266 异种移植模型中的恶性增殖和肿瘤干细胞样特性。我们的结果表明，lncRNA ANRIL 通过调节 HIF-1α 促进多发性骨髓瘤的恶性增殖和肿瘤干细胞样特性。
