Comprehensive Breast Health Center, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Rui-Jin Er Road, Shanghai, 200025, China.
Department of Pharmacy, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, No. 2800, Gong-Wei Road, Shanghai, 201399, China.
Biol Res. 2020 Sep 29;53(1):43. doi: 10.1186/s40659-020-00311-5.
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.
乳腺癌是全球女性最常见的癌症，导致了绝大多数与癌症相关的死亡。毫无疑问，肿瘤转移和复发是导致这些死亡的主要原因。miRNA 是内源性的非编码 RNA，已经整合到几乎所有的生理和病理过程中，包括转移。本研究探讨了 miR-128 在乳腺癌中的作用。
与相应的相邻正常组织相比，miR-128 在人乳腺癌标本中的表达明显受到抑制。更重要的是，其表达水平与癌症的组织学分级呈负相关。在侵袭性乳腺癌细胞系 MDA-MB-231 中异位表达 miR-128 可显著抑制细胞迁移和侵袭能力。随后，Metadherin（MTDH），也称为 AEG-1（Astrocyte Elevated Gene 1）和 Lyric，与癌症进展和转移的各个方面有关，被进一步鉴定为 miR-128 的直接靶基因，其表达水平在临床样本中如预期的那样上调。此外，在 MDA-MB-231 细胞中敲低 MTDH 明显削弱了迁移和侵袭能力，而重新表达 MTDH 则消除了 miR-128 引起的抑制作用。
总的来说，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，并可能成为未来治疗的潜在靶点。
