He Jiangtu, Mai Jieying, Li Yan, Chen Linyi, Xu Hui, Zhu Xiaofei, Pan Qiuhui
The Research Center for Immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
Department of Central Laboratory, Tenth People's Hospital of Tongji University, Shanghai 200072, P.R. China.
Oncol Rep. 2017 May;37(5):2672-2678. doi: 10.3892/or.2017.5558. Epub 2017 Apr 5.
Many reports suggest that the discovery of microRNAs (miRNAs) might provide a novel therapeutical target for many diseases, even of human cancers; however, there are no reports on the role of miR-597 in human cancers. In the present study, by detecting mRNA expression with qRT-PCR, compared with the adjacent normal tissues we found that miR-597 was significantly downregulated in breast cancer tissues. By using the MTT assay, the cell wound-healing assay and the cell invasion assay, we demonstrated that miR-597 mimics were able to suppress breast cancer cell proliferation, migration and invasion. Additionally, with flow cytometry, we found that mir-597 influenced the growth of breast cancer cells through regulating the G1-S phase transition. Furthermore, we identified one binding site for miR-597 at the 3'UTR of the FOSL2 gene, using bioinformatics methods and the luciferase reporter assay, it was confirmed that FOSL2 was a direct target of miR-597. Moreover, overexpression of FOSL2 in MDA-MB‑231 and SK-BR-3 cells can block the vast majority of the miR-597 roles, suggesting that miR-597 acts as a tumor suppressor in breast cancer cells by the downregulation of FOSL2. Additionally, we also found a negative correlation between the expression of FOSL2 and miR-597 in the tumor samples. This new regulatory mechanism in breast cancer may provide another method for diagnosis and therapy.
许多报告表明,微小RNA(miRNA)的发现可能为许多疾病,甚至人类癌症提供一种新的治疗靶点;然而,关于miR - 597在人类癌症中的作用尚无报道。在本研究中,通过qRT - PCR检测mRNA表达,与相邻正常组织相比,我们发现miR - 597在乳腺癌组织中显著下调。通过MTT法、细胞伤口愈合试验和细胞侵袭试验,我们证明miR - 597模拟物能够抑制乳腺癌细胞的增殖、迁移和侵袭。此外,通过流式细胞术,我们发现mir - 597通过调节G1 - S期转变影响乳腺癌细胞的生长。此外,我们在FOSL2基因的3'UTR处鉴定了一个miR - 597的结合位点,使用生物信息学方法和荧光素酶报告基因试验,证实FOSL2是miR - 597的直接靶点。此外,在MDA - MB‑231和SK - BR - 3细胞中过表达FOSL2可以阻断miR - 597的绝大多数作用,表明miR - 597通过下调FOSL2在乳腺癌细胞中发挥肿瘤抑制作用。此外,我们还发现肿瘤样本中FOSL2和miR - 597的表达呈负相关。这种乳腺癌中的新调控机制可能为诊断和治疗提供另一种方法。