Department of Hematology, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Pediatric Hematology, Shengjing Hospital of China Medical University, Shenyang, China.
Bioengineered. 2021 Dec;12(1):1611-1626. doi: 10.1080/21655979.2021.1920325.
Multiple myeloma (MM), a malignancy of plasma cells mainly derived from the bone marrow, has remained incurable generally. LncRNA MALAT1 has been reported to be upregulated in the MM cells and knockdown of MALAT1 inhibited MM cell cycle progression and enhanced cell apoptosis. Online target prediction showed that two target sites for MALAT1 existed in miR-188-5p, which has been identified as a tumor suppressor in other types of cancers. However, the role of miR-188-5p in the MM and whether miR-188-5p mediates the MM tumor progression regulated by MALAT1 are still unknown. Herein, four main MM cell lines were adopted to investigate the effects of miR-188-5p on cell proliferation and apoptosis via transfection with miR-188-5p mimic/inhibitor and co-transfection with miR-188-5p inhibitor and MALAT1-shRNA plasmids. Xenograft tumor model was also established to study these effects in vivo. Overexpression of miR-188-5p inhibited cell viability, cell proliferation as well as tumor growth and arrested cell cycle at G1 to S transition, but miR-188-5p knockdown showed opposite effects on the MM cells in vitro and in vivo. Moreover, MALAT1 was shown to be inversely correlated with miR-188-5p expression through direct binding to miR-188-5p, and in turn, miR-188-5p could mediate the MM cell proliferation and apoptosis regulated by MALAT1. These findings indicate that miR-188-5p serves as a tumor suppressor in the progression of the MM and is directly involved in MM cell proliferation and apoptosis regulated by MALAT1, which may provide a potential therapeutic target or prognostic indictor for MM clinical treatment.
多发性骨髓瘤（MM）是一种主要来源于骨髓的浆细胞恶性肿瘤，通常仍然无法治愈。已有研究报道长链非编码 RNA（lncRNA）MALAT1 在 MM 细胞中上调，敲低 MALAT1 可抑制 MM 细胞周期进程并增强细胞凋亡。在线靶标预测显示 MALAT1 存在 miR-188-5p 的两个靶位，miR-188-5p 已被确定为其他类型癌症中的肿瘤抑制因子。然而，miR-188-5p 在 MM 中的作用以及 miR-188-5p 是否介导 MALAT1 调节的 MM 肿瘤进展尚不清楚。在此，我们采用四种主要的 MM 细胞系，通过转染 miR-188-5p 模拟物/抑制剂以及共转染 miR-188-5p 抑制剂和 MALAT1-shRNA 质粒，研究 miR-188-5p 对细胞增殖和凋亡的影响。还建立了异种移植肿瘤模型，以研究这些效应在体内的作用。结果显示，过表达 miR-188-5p 抑制细胞活力、细胞增殖以及肿瘤生长，并使细胞周期停滞在 G1 到 S 期过渡，但 miR-188-5p 敲低在体外和体内对 MM 细胞则显示相反的效果。此外，MALAT1 与 miR-188-5p 的表达呈负相关，这是通过 MALAT1 直接与 miR-188-5p 结合实现的，而 miR-188-5p 可介导 MALAT1 调节的 MM 细胞增殖和凋亡。这些发现表明，miR-188-5p 作为 MM 进展中的肿瘤抑制因子，直接参与 MALAT1 调节的 MM 细胞增殖和凋亡，这可能为 MM 的临床治疗提供潜在的治疗靶点或预后指标。
