Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China.
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.
J Cell Mol Med. 2020 Mar;24(6):3492-3503. doi: 10.1111/jcmm.15035. Epub 2020 Feb 12.
Loss of one or some specific miRNA-mediated regulation is closely associated with malignant progression of multiple myeloma (MM). But how these miRNAs work and what role the specific miRNA plays in this process of malignant progression remain unclear. It was found in this study that the expression of miR-129 was decreased in both MM cell lines and newly diagnosed MM patients. Further clinicopathological statistics showed that miR-129 was correlated with the isotype of MM patients. MiR-129 overexpression disturbed cell proliferation, cell cycle evolution and spurred apoptosis both in vitro and in vivo. MAP3K7, a kinase able to activate NF-κB circuit, was found to be up-regulated in MM and contain a binding target of miR-129. In addition, lncRNA PCAT-1 functioned to sponge miR-129 and thereby lowered its expression. PCAT-1 knockdown eliminated the tumour-promoting effect caused by miR-129 inhibition, probably through repressing MAP3K7 and subsequent NF-κB activation. To the best of our knowledge, this is the first study to have discovered that increased expression of PCAT-1 could augment cell proliferation and cycle procession and inhibit apoptosis by down-regulating miR-129 via the MAP3K7/NF-κB pathway in MM.
某些特定的 miRNA 介导的调控丧失与多发性骨髓瘤（MM）的恶性进展密切相关。但是，这些 miRNA 如何发挥作用以及特定 miRNA 在恶性进展过程中扮演何种角色尚不清楚。本研究发现，miR-129 在 MM 细胞系和新诊断的 MM 患者中均表达下调。进一步的临床病理统计表明，miR-129 与 MM 患者的同种型相关。miR-129 的过表达在体外和体内均干扰细胞增殖、细胞周期演变并促进细胞凋亡。MAP3K7 是一种能够激活 NF-κB 通路的激酶，在 MM 中被发现上调并含有 miR-129 的结合靶位。此外，lncRNA PCAT-1 发挥海绵吸附 miR-129 的作用，从而降低其表达。PCAT-1 敲低消除了由 miR-129 抑制引起的促肿瘤作用，可能是通过抑制 MAP3K7 和随后的 NF-κB 激活。据我们所知，这是第一项研究，发现增加的 PCAT-1 表达可通过 MAP3K7/NF-κB 通路下调 miR-129 来增强 MM 中的细胞增殖、周期进程并抑制凋亡。
