Zhang Yuan, Tian Fei, Zhao Jing
Department of Gynecology, Hebei General Hospital, Shijiazhuang, Hebei, China.
Heliyon. 2023 Jul 28;9(8):e18789. doi: 10.1016/j.heliyon.2023.e18789. eCollection 2023 Aug.
MiR-520d-3p has recently been reported to have anti-tumor function in several cancers, including glioma and gastric cancer. However, the biological function and its mechanism of action remain unclear in cervical cancer (CC). In this study, we observed that miR-520d-3p expression was lowly expressed in CC specimens compared with adjacent normal specimens using reverse transcription quantitative PCR. Moreover, low miR-520d-3p expression was correlated with FIGO stage and lymph node metastasis by Chi-square test. Functionally, overexpression of miR-520d-3p suppressed the proliferation and migration and invasion of two CC cell lines (HeLa and SiHa) using CCK-8 assay and wound healing assay. After target prediction, luciferase reporter assay showed that zinc finger protein 36 ring finger protein-like 2 (ZFP36L2) was a direct target of miR-520d-3p in CC cells. The expression levels of ZFP36L2 at protein and mRNA were significantly increased in CC tissues compared with adjacent tissues. The expression of ZFP36L2 was negatively correlated with miR-520d-3p in the patients with CC. Importantly, ZFP36L2 overexpression abolished the effects of miR-520d-3p on cell proliferation, migration and EMT process in CC cells. In conclusion, our findings indicate that targeting miR-520d-3p/ZFP36L2 axis might be a promising therapeutic target for CC treatment.
最近有报道称,miR-520d-3p在包括胶质瘤和胃癌在内的多种癌症中具有抗肿瘤功能。然而,其在宫颈癌(CC)中的生物学功能及其作用机制仍不清楚。在本研究中,我们通过逆转录定量PCR观察到,与相邻正常标本相比,CC标本中miR-520d-3p表达较低。此外,通过卡方检验,低miR-520d-3p表达与国际妇产科联盟(FIGO)分期和淋巴结转移相关。在功能上,使用CCK-8检测和伤口愈合检测,miR-520d-3p的过表达抑制了两种CC细胞系(HeLa和SiHa)的增殖、迁移和侵袭。经过靶标预测,荧光素酶报告基因检测表明,锌指蛋白36环状指蛋白样2(ZFP36L2)是CC细胞中miR-520d-3p的直接靶标。与相邻组织相比,CC组织中ZFP36L2的蛋白质和mRNA表达水平显著升高。在CC患者中,ZFP36L2的表达与miR-520d-3p呈负相关。重要的是,ZFP36L2的过表达消除了miR-520d-3p对CC细胞增殖、迁移和上皮-间质转化(EMT)过程的影响。总之,我们的研究结果表明,靶向miR-520d-3p/ZFP36L2轴可能是CC治疗的一个有前景的治疗靶点。