miR-4652-3p/TWIST2轴调节乳腺癌血管生成及与超声造影参数的相关性

miR-4652-3p/TWIST2 axis regulates breast cancer angiogenic mimicry and its correlation with contrast-enhanced ultrasound parameters

目的探究miR-4652-3p对乳腺癌细胞增殖及血管生成的作用及与超声造影参数的相关性。方法qRT-PCR检测乳腺癌组织及细胞miR-4652-3p表达,生物信息学分析TWIST2 mRNA 3’-非翻译区miR-4652-3p的潜在结合位点,双荧光素酶报告基因实验验证,qRT-PCR及Western blot检测过表达miR-4652-3p对乳腺癌细胞TWIST2 mRNA和蛋白表达的影响,CCK-8检测乳腺癌细胞增殖。建立裸鼠成瘤模型,Western blot检测移植瘤AGGF1和VEGFA蛋白表达,超声造影检测移植瘤造影参数。结果miR-4652-3p在乳腺癌组织和细胞中低表达,miR-4652-3p靶向结合并抑制TWIST2表达,过表达miR-4652-3p抑制乳腺癌细胞增殖及肿瘤生长,降低移植瘤超声造影参数峰值强度,过表达TWIST2逆转miR-4652-3p对乳腺癌细胞增殖及肿瘤生长的抑制作用,增加移植瘤超声造影参数峰值强度。结论miR-4652-3p靶向抑制TWIST2表达抑制乳腺癌细胞增殖及肿瘤生长,且可通过超声造影进行评估。

Objective To explore the effect of miR-4652-3p on breast cancer cell proliferation and angiogenesis and its correlation with contrast-enhanced ultrasound parameters.Methods The expression of miR-4652-3p in breast cancer tissues and cells was detected by qRT-PCR,and the potential binding sites of miR-4652-3p in the 3’-untranslated region of TWIST2 mRNA were analyzed by bioinformatics.qRT-PCR and Western blot were used to detect the effect of overexpression of miR-4652-3p on the expression of TWIST2 mRNA and protein in breast cancer cells.CCK-8was used to detect the proliferation of breast cancer cells,and a tumorigenic model was established in nude mice.Western blot was used to detect the expressions of AGGF1 and VEGFA,and contrast-enhanced ultrasound was used to detect the contrast parameters.Results miR-4652-3p is lowly expressed in breast cancer tissues and cells.miR-4652-3p targeted binding and inhibited the expression of TWIST2.Overexpression of miR-4652-3p inhibited the proliferation of breast cancer cells and tumor growth,and reduced the peak intensity of contrast-enhanced ultrasound parameters for transplanted tumors.Overexpression of TWIST2 reversed the inhibitory effect of miR-4652-3p on the proliferation of breast cancer cells and tumor growth,and increased the peak intensity of CEUS parameters.Conclusion miR-4652-3p targeted inhibition of TWIST2 expression inhibited proliferation of breast cancer cells and tumor growth,and was evaluated by contrast-enhanced ultrasound.