Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Hematology, ChongQing Three Gorges Centre Hospital, Chongqing, China.
J Chin Med Assoc. 2019 Sep;82(9):699-709. doi: 10.1097/JCMA.0000000000000145.
Long noncoding RNAs (lncRNAs) are considered to be a novel prognostic and therapeutic target in many cancers. This study identified dysregulation of lncRNA urothelial carcinoma associated 1 (UCA1) and hepatocyte growth factor (HGF) mRNA via the Gene Expression Omnibus (GEO) database, which was traced to the mutual target miRNA, miR-1271-5p, and their effects were explored in multiple myeloma (MM).
RNA expression profiles of MM were downloaded from the GEO database and analyzed using R packages. The expression of RNAs in MM tissue samples and cells was evaluated through quantificational real-time polymerase chain reaction (qRT-PCR). A luciferase reporter assay was utilized to confirm the binding relationships between UCA1/HGF and miR-1271-5p. To assess cell proliferation and apoptosis, CCK-8 assays and flow cytometry were conducted. Additionally, tumor progression was demonstrated in vivo.
LncRNA UCA1 and HGF expression was higher in the cells and samples of patients with MM than in normal plasma cells. miR-1271-5p was confirmed to be the target of lncRNA UCA1 and HGF and to be negatively correlated with them. Moreover, downregulation of lncRNA UCA1 and HGF inhibited cell proliferation and facilitated cell apoptosis in RPMI 8226 cells (human MM cell line). However, miR-1271-5p overexpression affected the proliferation decrease and apoptosis increase. Moreover, in vivo experiments indicated that down or upregulation of lncRNA UCA1 repressed or enhanced the tumor growth of MM, respectively, in xenograft models.
LncRNA UCA1 promoted proliferation and inhibited apoptosis by regulating miR-1271-5p and HGF in the human MM cell line RPMI 8226. Our investigations might contribute to a better understanding of the lncRNA UCA1/miR-1271-5p/HGF axis as a potential therapeutic strategy in MM.
长链非编码 RNA（lncRNA）被认为是许多癌症中一种新的预后和治疗靶点。本研究通过基因表达综合数据库（GEO）鉴定了 lncRNA 尿路上皮癌相关 1（UCA1）和肝细胞生长因子（HGF）mRNA 的失调，该失调可追踪到共同的靶 miRNA，miR-1271-5p，并在多发性骨髓瘤（MM）中探讨了它们的作用。
从 GEO 数据库下载 MM 的 RNA 表达谱，并使用 R 包进行分析。通过定量实时聚合酶链反应（qRT-PCR）评估 MM 组织样本和细胞中的 RNA 表达。利用荧光素酶报告基因实验证实 UCA1/HGF 与 miR-1271-5p 的结合关系。通过 CCK-8 测定和流式细胞术评估细胞增殖和凋亡。此外，在体内证明肿瘤进展。
与正常浆细胞相比，MM 患者的细胞和样本中 lncRNA UCA1 和 HGF 的表达升高。miR-1271-5p 被证实是 lncRNA UCA1 和 HGF 的靶标，与它们呈负相关。此外，下调 lncRNA UCA1 和 HGF 抑制 RPMI 8226 细胞（人 MM 细胞系）中的细胞增殖并促进细胞凋亡。然而，miR-1271-5p 的过表达影响增殖减少和凋亡增加。此外，体内实验表明，在异种移植模型中，下调或上调 lncRNA UCA1 分别抑制或增强 MM 的肿瘤生长。
lncRNA UCA1 通过调节 miR-1271-5p 和 HGF 在人 MM 细胞系 RPMI 8226 中促进增殖并抑制凋亡。我们的研究可能有助于更好地理解 lncRNA UCA1/miR-1271-5p/HGF 轴作为 MM 的潜在治疗策略。
