VEGF-C调节miR-145/SIP1增强宫颈癌细胞侵袭能力

VEGF-C Promotes Cervical Cancer Invasion via Regulation of microRNA-145/Smad Interacting Protein 1

【目的】研究VEGF-C促子宫颈癌细胞侵袭能力的影响,探讨micro RNA-145/Smad相互作用蛋白1在其中的作用。【方法】体外培养宫颈癌细胞株SiHa细胞,观察VEGF-C对miR-145、SIP1表达的影响;转染SIP1si RNA后,采用transwell侵袭小室法观察其对宫颈癌细胞株增殖和侵袭的影响。【结果】VEGF-C(100 ng/mL)处理SiHa细胞12、24、48 h后,均能抑制miR-145表达,与对照组比较,其表达幅度分别为(82.4±6.4)%(P<0.05)、(72.5±7.2)%(P<0.01)、(60.6±9.6)%(P<0.001)。同时,VEGF-C处理后可增强SIP1蛋白表达,与对照组(100%)比较,表达幅度分别为(142.4±16.5)%(P<0.05)、(183.6±11.4)%(P<0.01)、(220.8±15.7)%(P<0.001)。miR-145类似物(mimic)可显著抑制VEGF-C促SIP1表达的效应。SiHa细胞转染特异性SIP1 siRNA 48 h后,VEGF-C促细胞侵袭的能力明显减弱,抑制率为(56.6±10.3)%(P<0.01)。【结论】VEGF-C可能下调miR-145,进而上调SIP1蛋白表达,增强宫颈癌侵袭能力及其恶性进展。

【Objective】To investigate the role of microRNA-145/Smad interacting protein1(SIP1)in VEGF-C-enhancedcervical cancer metastasis.【Methods】Cervical cancer cell line SiHa cells were cultured and treated with VEGF-C to observe its effect on the expression of miR-145and SIP1.After transfection with specific SIP1siRNA,the invasion number of cultured cells were calculated by transwell chamber assay.【Results】Treatment with VEGF-C(100ng/mL)for12h,24h and48h all reduced miR-145expression,with the expression abundance of(82.4±6.4)%(P<0.05),(72.5±7.2)%(P<0.01),and(60.6±9.6)%(P<0.001),respectively,when compared to control.Meanwhile,the same treatment with VEGF-C also increased SIP1protein expression,with the expression abundance of(142.4±16.5)%(P<0.05),(183.6±11.4)%(P<0.01)and(220.8±15.7)%(P<0.001),respectively.The transfection of miR-145mimic significantly impaired VEGF-C effect on SIP1expression.Finally,VEGF-C promoted SiHa cell invasion,which was largely inhibited by the tranfection of SIP siRNA with the inhibitory rate of(56.6±10.3)%(P<0.01).【Conclusion】VEGF-C downregulates miR-145,thus increases SIP1expression and promotes cervical cancer cell invasion,which may contributes to cervical cancer malignant progression.