长链非编码 RNA MALAT1/miR-181a-5p 通过调节 Hippo-YAP 信号通路影响骨髓瘤细胞的增殖和黏附。
LncRNA MALAT1/miR-181a-5p affects the proliferation and adhesion of myeloma cells via regulation of Hippo-YAP signaling pathway.
机构信息
Department of Nephrology, The Third Affiliated Hospital of Soochow University , Changzhou , China.
Department of Hematology, Liuzhou Worker's Hospital, The Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China.
出版信息
Cell Cycle. 2019 Oct;18(19):2509-2523. doi: 10.1080/15384101.2019.1652034. Epub 2019 Aug 9.
Multiple myeloma (MM) is a plasma cells malignant proliferative disease, especially in aged people. LncRNAs have been considered as important regulators in MM. This research was to study the effect of LncRNA MALAT1 on the proliferation and adhesion of myeloma cells and whether Long non-coding RNAs MALAT1(LncRNA MALAT1) plays its regulative role through Hippo-YAP signaling pathway by targeting miR-181a-5p. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was used to detect the LncRNA MALAT1/miR-181a-5p expression and improve the transfection efficiency. Western blot analysis was used to analyze the expression of proliferation and apoptosis related proteins and Hippo-Yes-associated protein (YAP) signaling pathway related proteins. Cell proliferative ability and cell apoptosis were respectively determined by Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis. ELISA assay was for the determination of adherence factors. Immunohistochemistry was to detect the expression of proliferation and adhesion related proteins. LncRNA MALAT1 targeting gene was determined by Dual-luciferase reporter assay. LncRNA MALAT1 was increased in MM cells and LncRNA MALAT1 interference could inhibit cell proliferation and promote cell apoptosis with the changes in the related proteins. Also, LncRNA MALAT1 interference could inhibit cell adhesion through Hippo-YAP signaling pathway. MiR-181a-5p was demonstrated to be a target of LncRNA MALAT1 and miR-181a-5p overexpression could also regulate the changes in cellular behavior in accordance with the LncRNA MALAT1 interference. In addition, LncRNA MALAT1 interference could decrease the expression of miR-181a-5p and inhibit the growth of tumor. In conclusion, this study showed that LncRNA MALAT1 interference inhibited the proliferation and adhesion of myeloma cells by the up-regulation of miR-181a-5p through activating the Hippo-YAP signaling pathway.
多发性骨髓瘤（MM）是一种浆细胞恶性增殖性疾病，尤其在老年人中多见。LncRNAs 已被认为是 MM 中的重要调节因子。本研究旨在探讨 LncRNA MALAT1 对骨髓瘤细胞增殖和黏附的影响，以及 LncRNA MALAT1 是否通过靶向 miR-181a-5p 发挥其调节作用通过 Hippo-YAP 信号通路。采用逆转录定量聚合酶链反应（RT-qPCR）分析检测 LncRNA MALAT1/miR-181a-5p 的表达并提高转染效率。Western blot 分析用于分析增殖和凋亡相关蛋白以及 Hippo-Yes 相关蛋白（YAP）信号通路相关蛋白的表达。通过细胞计数试剂盒-8（CCK-8）测定法和流式细胞术分析分别测定细胞增殖能力和细胞凋亡。酶联免疫吸附试验（ELISA）用于测定黏附因子。免疫组织化学用于检测增殖和黏附相关蛋白的表达。通过双荧光素酶报告基因检测确定 LncRNA MALAT1 的靶基因。结果表明，LncRNA MALAT1 在 MM 细胞中表达增加，LncRNA MALAT1 干扰可抑制细胞增殖，促进细胞凋亡，相关蛋白表达发生变化。此外，LncRNA MALAT1 干扰可通过 Hippo-YAP 信号通路抑制细胞黏附。miR-181a-5p 被证明是 LncRNA MALAT1 的靶基因，miR-181a-5p 的过表达也可以根据 LncRNA MALAT1 干扰调节细胞行为的变化。此外，LncRNA MALAT1 干扰可降低 miR-181a-5p 的表达并抑制肿瘤生长。综上所述，本研究表明，LncRNA MALAT1 干扰通过激活 Hippo-YAP 信号通路上调 miR-181a-5p 抑制骨髓瘤细胞的增殖和黏附。
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