miR-337-3p 及其靶基因 Rap1A 在调控宫颈癌细胞增殖、侵袭、迁移和凋亡中的作用。

Role of miR-337-3p and its target Rap1A in modulating proliferation, invasion, migration and apoptosis of cervical cancer cells.

出版信息

Cancer Biomark. 2019;24(3):257-267. doi: 10.3233/CBM-181225.

Abstract

OBJECTIVE

To investigate the role of miR-337-3p targeting Rap1A in modulating proliferation, invasion, migration and apoptosis of cervical cancer cells.

METHODS

The expression levels of miR-337-3p and Rap1A in cervical cancer tissues and normal tissues were evaluated through quantitative Real-time PCR (qRT-PCR) and Western blotting; and correlations of miR-337-3p with clinicopathological characteristics and prognosis of patients were also analyzed. Besides, human cervical cancer cell line HeLa cells were randomly divided into five groups (Mock, NC, miR-337-3p mimic, Rap1A, and miR-337-3p mimic + Rap1A groups). CCK-8 assay was utilized to measure cell proliferation, flow cytometry to evaluate cell apoptosis, and wound-healing and Transwell assays to detect cell migration and invasion.

RESULTS

Cervical cancer tissues presented a significant decrease in miR-337-3p and a remarkable increase in Rap1A protein. Besides, the expression levels of miR-337-3p and Rap1A were closely related to the major clinicopathological characteristics of cervical cancer; and patients with high-miR-337-3p-expression had the higher 5-year survival rate (all p< 0.05). When compared to Mock group, cells in miR-337-3p mimic group were suppressed in proliferation, migration, and invasion, but significantly promoted in apoptosis; meanwhile, cells in the Rap1A group showed changes in a completely opposite trend (all p< 0.05). Moreover, Rap1A can reverse the effect of miR-337-3p mimic on cell proliferation, invasion, migration and apoptosis (all p< 0.05).

CONCLUSION

MiR-337-3p was discovered to be decreased in cervical cancer, and miR-337-3p up-regulation may inhibit the proliferation, migration and invasion and promote the apoptosis of cervical cancer cells via down-regulating Rap1A.

摘要

目的

研究 miR-337-3p 靶向 Rap1A 对调控宫颈癌细胞增殖、侵袭、迁移和凋亡的作用。

方法

通过实时定量 PCR（qRT-PCR）和 Western blot 检测 miR-337-3p 和 Rap1A 在宫颈癌组织和正常组织中的表达水平，并分析 miR-337-3p 与患者临床病理特征和预后的相关性。此外，将人宫颈癌 HeLa 细胞随机分为 5 组（Mock 组、NC 组、miR-337-3p 模拟组、Rap1A 组和 miR-337-3p 模拟+Rap1A 组）。CCK-8 法检测细胞增殖，流式细胞术检测细胞凋亡，划痕愈合和 Transwell 检测细胞迁移和侵袭。

结果

宫颈癌组织中 miR-337-3p 显著降低，Rap1A 蛋白显著升高。此外，miR-337-3p 和 Rap1A 的表达水平与宫颈癌的主要临床病理特征密切相关；高 miR-337-3p 表达的患者 5 年生存率更高（均 p<0.05）。与 Mock 组相比，miR-337-3p 模拟组细胞增殖、迁移和侵袭受到抑制，凋亡明显增加；而 Rap1A 组则表现出完全相反的变化趋势（均 p<0.05）。此外，Rap1A 可逆转 miR-337-3p 模拟对细胞增殖、侵袭、迁移和凋亡的影响（均 p<0.05）。