Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
J Cell Biochem. 2018 Mar;119(3):2617-2626. doi: 10.1002/jcb.26426. Epub 2017 Dec 12.
MicroRNA-29 (miR-29) family is involved in various types of cancer regulation. Although miR-29 family was shown to play an inhibitory role in tumorigenesis, the effect of miR-29a expression on schwannoma cells still remains unclear. In this study, we aimed to explore the role of miR-29 family in schwannoma. The expressions of miR-29a, miR-29b, and miR-29c were detected in the Schwann tissues and cell lines using qRT-PCR. The effect of miR-29a, miR-29b, and miR-29c on cell viability, migration, invasion, and apoptosis was tested. Then, the regulatory relationship between miR-29a and CKD6 was detected using qRT-PCR, Western blot, and luciferase assay. Finally, the phosphorylation levels of mainly factors in JNK and p38MAPK/ERK pathways were analyzed by Western blot. The expression of miR-29a, miR-29b, and miR-29c was downregulated in Schwann tissues and cell lines. Cell viability, migration, invasion were decreased, while apoptosis was increased when miR-29a, miR-29b, and miR-29c overexpression. We further found that miR-29a negatively regulated expression of CDK6. Then, knockdown of miR-29a promoted cell viability, migration, invasion, and inhibited apoptosis in schwannoma cells by upregulating CDK6 expression. In addition, the overexpression of miR-29a downregulated CDK6 expression by deactivation of JNK and p38MAPK/ERK pathways. Our data suggested that miR-29a could play an important role in inhibiting proliferation and motility of cancerous Schwann cells, and may suppress tumor growth through upregulation of CDK6.
miR-29 家族参与多种类型癌症的调控。尽管 miR-29 家族在肿瘤发生中发挥抑制作用，但 miR-29a 表达对神经鞘瘤细胞的影响仍不清楚。本研究旨在探讨 miR-29 家族在神经鞘瘤中的作用。采用 qRT-PCR 检测 miR-29a、miR-29b 和 miR-29c 在神经鞘组织和细胞系中的表达。检测 miR-29a、miR-29b 和 miR-29c 对细胞活力、迁移、侵袭和凋亡的影响。然后，采用 qRT-PCR、Western blot 和荧光素酶报告基因检测 miR-29a 与 CKD6 的调控关系。最后，采用 Western blot 分析 JNK 和 p38MAPK/ERK 通路中主要因子的磷酸化水平。miR-29a、miR-29b 和 miR-29c 在神经鞘组织和细胞系中表达下调。miR-29a、miR-29b 和 miR-29c 过表达可降低细胞活力、迁移和侵袭，促进细胞凋亡。我们进一步发现 miR-29a 负调控 CDK6 的表达。随后，miR-29a 敲低通过上调 CDK6 表达促进神经鞘瘤细胞的活力、迁移和侵袭，抑制凋亡。此外，miR-29a 的过表达通过抑制 JNK 和 p38MAPK/ERK 通路的失活下调 CDK6 表达。我们的数据表明，miR-29a 可能在抑制癌细胞增殖和运动中发挥重要作用，并可能通过上调 CDK6 抑制肿瘤生长。
