miR-184 通过靶向 Notch1 对多发性骨髓瘤的影响。

Effect of miR-184 on Multiple Myeloma by Targeting Notch1.

机构信息

Department of Lecturer, Wuchang Institute of Technology, Wuhan, China.

Department of Orthopedics, Yichang Traditional Chinese Medicine Hospital, Yichang, China.

出版信息

Ann Clin Lab Sci. 2024 Jul;54(4):533-538.

PMID:39293836

Abstract

OBJECTIVE

Multiple myeloma (MM) is caused by abnormal cloning of plasma cells. miR-184 is abnormally expressed in several types of tumors, but its expression and role in MM have not been reported.

METHODS

The bone marrow samples of healthy controls and MM patients were collected, and plasma cells were sorted. The multiple myeloma cell line OPM-2 was cultured and assigned into miR-NC+siRNA-NC group, miR-184 inhibitor+siRNA-NC group, and miR-184 inhibitor+siRNA-Notch1 group. Cell proliferation was assessed by MTT assay. Clone formation was evaluated by colony formation assay. Cell apoptosis activity was tested with flow cytometry. Notch1 and cleaved caspase3 protein expressions were detected.

RESULTS

MiR-184 expression was increased in myeloma plasma cells (<0.05). Transfection of miR-184 inhibitor can downregulate miR-184 expression, increase the levels of Notch1 and cleaved caspase3, inhibit OPM-2 cell proliferation, restrain colony formation, enhance caspase3 activity, and suppress tumor cell invasion (<0.05). However, administration of siRNA-Notch1 retarded the effect of miR-184 inhibitor by decreasing the expressions of Notch1 and cleaved caspase3, enhancing colony formation and tumor cell invasion, as well as inhibiting caspase3 activity and cell proliferation.

CONCLUSION

Our data indicated that miR-184 expression is increased in myeloma plasma cells. Down-regulation of miR-184 promotes MM cell apoptosis and inhibits proliferation and colony formation by regulating Notch1 expression.

摘要

目的

多发性骨髓瘤（MM）是由浆细胞异常克隆引起的。miR-184 在多种类型的肿瘤中异常表达，但它在 MM 中的表达和作用尚未被报道。

方法

收集健康对照者和 MM 患者的骨髓样本，并对浆细胞进行分选。培养多发性骨髓瘤细胞系 OPM-2，并分为 miR-NC+siRNA-NC 组、miR-184 抑制剂+siRNA-NC 组和 miR-184 抑制剂+siRNA Notch1 组。用 MTT 法评估细胞增殖。用集落形成实验评估克隆形成。用流式细胞术检测细胞凋亡活性。检测 Notch1 和 cleaved caspase3 蛋白的表达。

结果

骨髓瘤浆细胞中 miR-184 表达增加（<0.05）。转染 miR-184 抑制剂可下调 miR-184 表达，增加 Notch1 和 cleaved caspase3 水平，抑制 OPM-2 细胞增殖，抑制集落形成，增强 caspase3 活性，抑制肿瘤细胞侵袭（<0.05）。然而，siRNA Notch1 的给药通过降低 Notch1 和 cleaved caspase3 的表达、增强集落形成和肿瘤细胞侵袭、抑制 caspase3 活性和细胞增殖，削弱了 miR-184 抑制剂的作用。