Chen Ying, Hao Jinxia, Zhao Jing, Liu Ye, Li Yuan, Ren Juan, Wang Wei
Department of Hematology, The First Affiliated Hospital of Xi'an Jiaotong University China.
Department of Hematology, Ninth Hospital of Xi'an No. 151, East Section of South Second Ring Road Xi'an 710049 Shaanxi China
RSC Adv. 2019 Oct 21;9(58):33834-33842. doi: 10.1039/c9ra06188f. eCollection 2019 Oct 18.
Multiple Myeloma (MM) is a plasma cell myeloma. Long non-coding RNA (lncRNA) prostate cancer associated transcript 1 (PCAT1) has been identified as being associated with various types of cancer. However, the mechanism of PCAT1 was still undefined in MM. In the current study, PCAT1 and metadherin (MTDH) were up-regulated and miR-363-3p was down-regulated in MM bone marrow plasma and cells. Furthermore, PCAT1 knockdown inhibited cell proliferation, cell cycle progression, and the protein kinase B (AKT) and β-catenin signaling pathway, but induced cell apoptosis by regulating MTDH. PCAT1 was verified to sponge miR-363-3p, and MTDH was identified as a candidate target of miR-363-3p. Meanwhile, PCAT1 positively modulated MTDH expression by sponging miR-363-3p. In addition, PCAT1 knockdown blocked xenograft tumor growth . Thus, we concluded that PCAT1 facilitated cell growth in multiple myeloma by activating the AKT/β-catenin signaling pathway through the miR-363-3p/MTDH axis.
多发性骨髓瘤（MM）是一种浆细胞骨髓瘤。长链非编码RNA（lncRNA）前列腺癌相关转录本1（PCAT1）已被确定与多种类型的癌症相关。然而，PCAT1在MM中的作用机制仍不明确。在本研究中，MM骨髓浆细胞和细胞中PCAT1和黏附素（MTDH）上调，而miR-363-3p下调。此外，敲低PCAT1可抑制细胞增殖、细胞周期进程以及蛋白激酶B（AKT）和β-连环蛋白信号通路，但通过调节MTDH诱导细胞凋亡。经证实，PCAT1可吸附miR-363-3p，且MTDH被确定为miR-363-3p的候选靶标。同时，PCAT1通过吸附miR-363-3p正向调节MTDH表达。此外，敲低PCAT1可阻断异种移植瘤的生长。因此，我们得出结论，PCAT1通过miR-363-3p/MTDH轴激活AKT/β-连环蛋白信号通路促进多发性骨髓瘤细胞生长。
