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长链非编码 RNA CCAT1 通过作为 miR-181a-5p 的分子海绵来调节 HOXA1 表达,从而促进多发性骨髓瘤的进展。

Long non-coding RNA CCAT1 promotes multiple myeloma progression by acting as a molecular sponge of miR-181a-5p to modulate HOXA1 expression.

机构信息

a Department of Hematology , Huaihe Hospital of Henan University , Kaifeng 475000 , Henan China.

b Department of Hematology , The First People's Hospital of Shangqiu , Shangqiu 476100 , Henan China.

出版信息

Cell Cycle. 2018;17(3):319-329. doi: 10.1080/15384101.2017.1407893. Epub 2018 Jan 29.

Abstract

Multiple myeloma (MM) is the second most common hematological cancer all over the world. Long non-coding RNA (lncRNA) colon cancer associated transcript-1 (CCAT1) has been reported to play important roles in the development and progression of multiple human malignancies. However, little is known about its functional role and molecular mechanism in MM. The aim of this study was to investigate the clinical and biological significance of CCAT1 in MM. Our data showed that the relative expression levels of CCAT1 were significantly upregulated in MM tissues and cell lines compared with healthy donors and normal plasma cells (nPCs). High expression of CCAT1 was correlated shorter overall survival of MM patients. CCAT1 knockdown significantly inhibited cell proliferation, induced cell cycle arrest at G0/G1 phase and promoted cell apoptosis in vitro, and suppressed tumor growth in vivo. MiR-181a-5p was a direct target of CCAT1, and repression of miR-181a-5p could rescue the inhibition of CCAT1 knockdown on MM progression. In addition, CCAT1 positively regulated HOXA1 expression through sponging miR-181a-5p in MM cells.taken together, lncRNA CCAT1 exerted an oncogenic role in MM by acting as a ceRNA of miR-181a-5p. These results suggest that CCAT1 may serve as a novel diagnostic marker and therapeutic target for MM.

摘要

多发性骨髓瘤(MM)是全球第二大常见的血液系统恶性肿瘤。长链非编码 RNA(lncRNA)结肠癌相关转录本-1(CCAT1)已被报道在多种人类恶性肿瘤的发生和发展中发挥重要作用。然而,其在 MM 中的功能作用和分子机制知之甚少。本研究旨在探讨 CCAT1 在 MM 中的临床和生物学意义。我们的数据表明,与健康供体和正常浆细胞(nPC)相比,CCAT1 在 MM 组织和细胞系中的相对表达水平显著上调。CCAT1 高表达与 MM 患者的总生存期较短相关。CCAT1 敲低显著抑制体外细胞增殖,诱导 G0/G1 期细胞周期停滞,并促进细胞凋亡,体内抑制肿瘤生长。miR-181a-5p 是 CCAT1 的直接靶标,抑制 miR-181a-5p 可以挽救 CCAT1 敲低对 MM 进展的抑制作用。此外,CCAT1 通过海绵吸附 miR-181a-5p 在 MM 细胞中正向调节 HOXA1 表达。总之,lncRNA CCAT1 通过作为 miR-181a-5p 的 ceRNA 在 MM 中发挥致癌作用。这些结果表明,CCAT1 可能作为 MM 的新型诊断标志物和治疗靶点。

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