Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Department of Hematology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Cytokine. 2021 Jun;142:155495. doi: 10.1016/j.cyto.2021.155495. Epub 2021 Mar 23.
MicroRNA (MiR)-135b and its mediated Wnt/β-catenin signaling pathway are involved in human malignancies. However, their roles in multiple myeloma (MM) remained poorly understood. Our study aimed to uncover their roles in MM. MiR-135b and Versican expressions were measured using quantitative real-time polymerase chain reaction (qRT-PCR). MM cell proliferation, apoptosis, migration and invasion were detected by cell counting kit-8 (CCK-8) assay, flow cytometry, wound healing assay and transwell assay, respectively. Relative expression of Wnt/β-catenin signaling pathway-related protein was quantified by Western blot. MiR-135b was upregulated in the serum of MM patients, and miR-135b upregulation promoted MM cell proliferation, migration and invasion but suppressed apoptosis. Also, miR-135b upregulation promoted activation of Wnt/β-catenin signaling pathway. However, downregulation of miR-135b caused an opposite effect. After incubating cells with miR-135b inhibitor and Wnt/β-catenin signaling pathway agonist Lithium chloride (LiCl), which reversed the effects of downregulating miR-135b. Versican is the downstream effector of the Wnt/β-catenin signaling pathway, and its silencing reversed the effects of LiCl on MM cells. In conclusion, miR-135b and its mediated Wnt/β-catenin signaling pathway promoted proliferation, migration and invasion but suppressed apoptosis of MM cells through regulating Versican, providing a possible treatment for MM.
微小 RNA（miR）-135b 及其介导的 Wnt/β-catenin 信号通路参与人类恶性肿瘤。然而，它们在多发性骨髓瘤（MM）中的作用仍知之甚少。本研究旨在揭示它们在 MM 中的作用。采用实时定量聚合酶链反应（qRT-PCR）检测 miR-135b 和 Versican 的表达。通过细胞计数试剂盒-8（CCK-8）检测、流式细胞术、划痕愈合试验和 Transwell 试验分别检测 MM 细胞增殖、凋亡、迁移和侵袭。Western blot 定量检测 Wnt/β-catenin 信号通路相关蛋白的相对表达量。MM 患者血清中 miR-135b 上调，miR-135b 上调促进 MM 细胞增殖、迁移和侵袭，抑制凋亡。此外，miR-135b 上调促进 Wnt/β-catenin 信号通路的激活。然而，下调 miR-135b 则会产生相反的效果。用 miR-135b 抑制剂和 Wnt/β-catenin 信号通路激动剂氯化锂（LiCl）孵育细胞后，这种下调 miR-135b 的作用被逆转。Versican 是 Wnt/β-catenin 信号通路的下游效应物，其沉默逆转了 LiCl 对 MM 细胞的作用。总之，miR-135b 及其介导的 Wnt/β-catenin 信号通路通过调节 Versican 促进 MM 细胞的增殖、迁移和侵袭，抑制凋亡，为 MM 的治疗提供了一种可能的方法。
