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MicroRNA-425 induces apoptosis and suppresses migration and invasion of human cervical cancer cells by targeting RAB2B
International Journal of Immunopathology and Pharmacology ( IF 3.0 ) Pub Date : 2021-05-22 , DOI: 10.1177/20587384211016131
Yue Tian 1 , Ying Luo 1 , Jing Wang 2
Affiliation  

Dysregulation of microRNA-425 (miR-425) has been reported in several human cancers. However, the role of miR-425 in human cervical cancer via modulation of RAB2B expression is still unclear. This study was therefore designed to examine the expression and decipher the role of miR-425 in cervical cancer. The qRT-PCR was used for expression analysis. MTT and EdU assays were used for the determination of cell viability and proliferation, respectively. Annexin V/PI staining was used to detect apoptosis. Wound healing and transwell assays were used to monitor cell migration and invasion. Western blotting was used for protein expression analysis. The in vivo study was performed in xenografted mice model. The results of the present study revealed miR-425 to be significantly (P = 0.032) down-regulated in cervical cancer tissues and cell lines. Additionally, low expression of miR-425 was associated with significantly (P = 0.035) lower survival rate of the cervical cancer patients. Overexpression of miR-425 resulted in significant (P = 0.024) decline of cervical cancer cell proliferation via induction of apoptosis. The induction of apoptosis was associated with up-regulation of Bax and down-regulation of Bcl-2. Besides, the migration and invasion of cancer cells significantly (P < 0.01) decreased under miR-425 overexpression. Additionally, miR-425 could inhibit the growth of xenografted tumors in vivo. In silico analysis and dual luciferase assay revealed RAB2B as the direct target of miR-425 in cervical cancer. RAB2B was found to be significantly (P < 0.05) up-regulated in cervical cancer tissues and cell lines and miR-425 overexpression suppressed the expression of RAB2B. Additionally, silencing of RAB2B could suppress the growth of cervical cancer cells but its overexpression could rescue the tumor-suppressive effects of miR-425. Taken together, the results revealed the tumor-suppressive roe of miR-425 and point towards its therapeutic potential in the management of cervical cancer.



中文翻译:


MicroRNA-425通过靶向RAB2B诱导细胞凋亡并抑制人宫颈癌细胞的迁移和侵袭



据报道,多种人类癌症中存在 microRNA-425 (miR-425) 失调。然而,miR-425 通过调节 RAB2B 表达在人宫颈癌中的作用仍不清楚。因此,本研究旨在检查 miR-425 在宫颈癌中的表达并破译其作用。 qRT-PCR用于表达分析。 MTT 和 EdU 测定分别用于测定细胞活力和增殖。膜联蛋白V/PI染色用于检测细胞凋亡。伤口愈合和跨孔实验用于监测细胞迁移和侵袭。蛋白质印迹用于蛋白质表达分析。体内研究是在异种移植小鼠模型中进行的。本研究结果显示,miR-425在宫颈癌组织和细胞系中显着下调( P = 0.032)。此外,miR-425的低表达与宫颈癌患者的生存率显着降低( P = 0.035)相关。 miR-425 的过表达通过诱导细胞凋亡导致宫颈癌细胞增殖显着下降( P = 0.024)。细胞凋亡的诱导与 Bax 的上调和 Bcl-2 的下调有关。此外,miR-425过表达时癌细胞的迁移和侵袭能力显着降低( P < 0.01)。此外,miR-425可以抑制体内异种移植肿瘤的生长。计算机分析和双荧光素酶测定显示 RAB2B 是 miR-425 在宫颈癌中的直接靶标。研究发现,RAB2B 在宫颈癌组织和细胞系中显着上调( P < 0.05),并且 miR-425 过表达抑制 RAB2B 的表达。 此外,RAB2B 的沉默可以抑制宫颈癌细胞的生长,但其过度表达可以挽救 miR-425 的肿瘤抑制作用。总而言之,这些结果揭示了 miR-425 的肿瘤抑制作用,并表明其在宫颈癌治疗中的治疗潜力。

更新日期:2021-05-22
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