Clinical Laboratory Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu, China.
J Healthc Eng. 2022 Jan 25;2022:3282860. doi: 10.1155/2022/3282860. eCollection 2022.
Multiple myeloma is one of the hematological malignancies and inhibited osteoblast differentiation of bone marrow mesenchymal stem cells (BM-MSCs) which has been proved as a major complication of the patients with multiple myeloma. However, the pathomechanism of symptom remains unclear. Besides, several studies have indicated that LINC00461 plays an important role in the progression of multiple tumors. Hence, this study attempted to reveal the role of LINC00461 in the osteoblast differentiation of MSCs. In this study, the expression level of LINC00461 in the exosomes of multiple myeloma cells was measured, and BM-MSCs were cultured with the exosomes to observe the change of cellular phenotype. Moreover, downstream target of LINC00461 was searched and verified with dual-luciferase reporter assay, and the activation of the Wnt/-catenin pathway was also observed by Western blot. The results showed that the isolated BMSCs exhibited special biomarkers of MSCs. LINC00461 was significantly upregulated in the exosomes originated multiple myeloma cells, and increased LINC00461 significantly impeded the osteoblast differentiation of MSCs. Moreover, LINC00461 could significantly suppress the activation of the Wnt/-catenin pathway in MSCs. In conclusion, this study suggested that LINC00461 in exosomes of multiple myeloma could reduce the activity of the Wnt/-catenin pathway to inhibit the osteoblast differentiation of BM-MSCs via targeting miR-324-3p.
多发性骨髓瘤是一种血液系统恶性肿瘤,可抑制骨髓间充质干细胞(BM-MSCs)的成骨细胞分化,这已被证明是多发性骨髓瘤患者的主要并发症之一。然而,其症状的发病机制仍不清楚。此外,有几项研究表明 LINC00461 在多种肿瘤的进展中起着重要作用。因此,本研究试图揭示 LINC00461 在 MSC 成骨细胞分化中的作用。在这项研究中,测量了多发性骨髓瘤细胞外体中 LINC00461 的表达水平,并培养 BM-MSCs 与外体共培养,观察细胞表型的变化。此外,通过双荧光素酶报告基因实验搜索并验证了 LINC00461 的下游靶标,并通过 Western blot 观察了 Wnt/-catenin 通路的激活情况。结果表明,分离的 BMSCs 表现出 MSC 的特殊生物标志物。多发性骨髓瘤细胞来源的外体中 LINC00461 显著上调,增加的 LINC00461 显著阻碍了 MSC 的成骨细胞分化。此外,LINC00461 可显著抑制 MSC 中 Wnt/-catenin 通路的激活。总之,本研究表明,多发性骨髓瘤细胞外体中的 LINC00461 通过靶向 miR-324-3p 降低 Wnt/-catenin 通路的活性,从而抑制 BM-MSCs 的成骨细胞分化。