Xie Wei, Sun Feng, Chen Lin, Cao Xinjian
Department of Laboratory Medicine, Nantong First People's Hospital, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
Department of Laboratory Medicine, Nantong Tumor Hospital, Nantong, Jiangsu 226361, P.R. China.
Oncol Lett. 2018 Mar;15(3):3464-3471. doi: 10.3892/ol.2018.7728. Epub 2018 Jan 4.
Novel, non-invasive biomarkers with high sensitivity and specificity are critical for breast cancer treatment, and prognosis. MicroRNA (miR)-96 has been demonstrated to be highly expressed in several solid malignancies, including breast cancer. However, its expression and function in the metastasis and prognosis of breast cancer have not been fully explored, and its regulation mechanisms remain unclear. In the present study, the serum miR-96 expression in healthy controls, benign and malignant breast cancer types was compared by using reverse transcription-quantitative polymerase chain reaction. The effect of chemotherapy on miR-96 expression in breast cancer was also investigated. Result revealed that miR-96 expression was increased in malignant breast cancer types and reduced in patients following chemotherapy treatment. The effect of miR-96 manipulation on the migration of breast cancer cells was also investigated by using wound healing, and Transwell migration assays. These results revealed that the induced expression of miR96 led to enhanced wound closing and trans-membrane cell numbers. By using bioinformatics analysis, western blotting and immunohistochemical staining, the metastasis suppressor-1 (MTSS1) gene was identified to be the functional target of miR-96 in the promotion of cell migration. In conclusion, it was identified that miR-96 exhibited an increased level in serum samples of patients with malignant breast cancer in comparison with benign breast tumor types and health controls and may be substantially reduced by chemotherapy treatment, implying that it may be used as a prognostic marker in breast cancer. miR-96 overexpression may inhibit migration of breast cancer cells by downregulating MTSS1 expression.
新型、具有高灵敏度和特异性的非侵入性生物标志物对于乳腺癌的治疗和预后至关重要。微小RNA(miR)-96已被证明在包括乳腺癌在内的多种实体恶性肿瘤中高表达。然而,其在乳腺癌转移和预后中的表达及功能尚未得到充分研究,其调控机制也仍不清楚。在本研究中,通过逆转录-定量聚合酶链反应比较了健康对照、良性和恶性乳腺癌类型患者血清中miR-96的表达。还研究了化疗对乳腺癌中miR-96表达的影响。结果显示,恶性乳腺癌类型中miR-96表达增加,化疗治疗后的患者中miR-96表达降低。还通过伤口愈合实验和Transwell迁移实验研究了miR-96调控对乳腺癌细胞迁移的影响。这些结果表明,miR96的诱导表达导致伤口闭合增强和跨膜细胞数量增加。通过生物信息学分析、蛋白质免疫印迹和免疫组织化学染色,确定转移抑制因子1(MTSS1)基因是miR-96促进细胞迁移的功能靶点。总之,研究发现与良性乳腺肿瘤类型和健康对照相比,恶性乳腺癌患者血清样本中miR-96水平升高,且化疗治疗后可能大幅降低,这意味着它可能作为乳腺癌的预后标志物。miR-96过表达可能通过下调MTSS1表达来抑制乳腺癌细胞的迁移。