Breast cancer, the most common cancer in women worldwide, causes the vast majority of cancer-related deaths. Undoubtedly, tumor metastasis and recurrence are responsible for more than 90 percent of these deaths. MicroRNAs are endogenous noncoding RNAs that have been integrated into almost all the physiological and pathological processes, including metastasis. In the present study, the role of miR-128 in breast cancer was investigated. Compared to the corresponding adjacent normal tissue, the expression of miR-128 was significantly suppressed in human breast cancer specimens. More importantly, its expression level was reversely correlated to histological grade of the cancer. Ectopic expression of miR-128 in the aggressive breast cancer cell line MDA-MB-231 could inhibit cell motility and invasive capacity remarkably. Afterwards, Metadherin (MTDH), also known as AEG-1 (Astrocyte Elevated Gene 1) and Lyric that implicated in various aspects of cancer progression and metastasis, was further identified as a direct target gene of miR-128 and its expression level was up-regulated in clinical samples as expected. Moreover, knockdown of MTDH in MDA-MB-231 cells obviously impaired the migration and invasion capabilities, whereas re-expression of MTDH abrogated the suppressive effect caused by miR-128. Overall, these findings demonstrate that miR-128 could serve as a novel biomarker for breast cancer metastasis and a potent target for treatment in the future.

中文翻译：

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MiR-128通过靶向乳腺癌细胞中的metaherin抑制转移能力

乳腺癌是全世界女性中最常见的癌症，它导致绝大多数与癌症相关的死亡。毫无疑问，肿瘤转移和复发是造成这些死亡的90％以上。MicroRNA是内源性非编码RNA，已经整合到几乎所有生理和病理过程中，包括转移。在本研究中，对miR-128在乳腺癌中的作用进行了研究。与相应的相邻正常组织相比，miR-128的表达在人乳腺癌样本中得到了显着抑制。更重要的是，它的表达水平与癌症的组织学等级成反比。miR-128在侵袭性乳腺癌细胞系MDA-MB-231中的异位表达可显着抑制细胞运动和侵袭能力。之后，Metadherin（MTDH），也被称为AEG-1（星形胶质细胞升高基因1）和Lyric，与癌症进展和转移的各个方面都有牵连，被进一步鉴定为miR-128的直接靶基因，其表达水平在临床样品中如预期的那样上调。此外，MTDH在MDA-MB-231细胞中的敲低明显损害了迁移和侵袭能力，而MTDH的重新表达则消除了miR-128引起的抑制作用。总体而言，这些发现表明，miR-128可以作为乳腺癌转移的新型生物标志物，并且可以作为未来治疗的有效靶标。进一步将其鉴定为miR-128的直接靶基因，并且其表达水平在临床样品中如预期的那样上调。此外，MTDH在MDA-MB-231细胞中的敲低明显损害了迁移和侵袭能力，而MTDH的重新表达则消除了miR-128引起的抑制作用。总体而言，这些发现表明，miR-128可以作为乳腺癌转移的新型生物标志物，并在将来成为治疗的有效靶标。进一步将其鉴定为miR-128的直接靶基因，并且其表达水平在临床样品中如预期的那样上调。此外，MTDH在MDA-MB-231细胞中的敲低明显损害了迁移和侵袭能力，而MTDH的重新表达则消除了miR-128引起的抑制作用。总体而言，这些发现表明，miR-128可以作为乳腺癌转移的新型生物标志物，并在将来成为治疗的有效靶标。