Zhan Meng-Na, Yu Xiao-Ting, Tang Jun, Zhou Ci-Xiang, Wang Chen-Long, Yin Qian-Qian, Gong Xiu-Feng, He Ming, He Jian-Rong, Chen Guo-Qiang, Zhao Qian
Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
Department of Pathology, Tong-Ji Hospital Affiliated to Tong-Ji University School of Medicine, Shanghai, China.
Cell Death Dis. 2017 Jan 5;8(1):e2529. doi: 10.1038/cddis.2016.440.
MicroRNA (miRNA) is involved in the progression and metastasis of diverse human cancers, including breast cancer, as strong evidence has been found that miRNAs can act as oncogenes or tumor suppressor genes. Here, we show that miR-494 is decreased in human breast cancer specimens and breast cancer cell lines. Ectopic expression of miR-494 in basal-like breast cancer cell lines MDA-MB-231-LUC-D2H3LN and BT-549 inhibits clonogenic ability and metastasis-relevant traits in vitro. Moreover, ectopic expression of miR-494 suppresses neoplasm initiation as well as pulmonary metastasis in vivo. Further studies have identified PAK1, as a direct target gene of miR-494, contributes to the functions of miR-494. Remarkably, the expression of PAK1 is inversely correlated with the level of miR-494 in human breast cancer samples. Furthermore, re-expression of PAK1 partially reverses miR-494-mediated proliferative and clonogenic inhibition as well as migration and invasion suppression in breast cancer cells. Taken together, these findings highlight an important role for miR-494 in the regulation of progression and metastatic potential of breast cancer and suggest a potential application of miR-494 in breast cancer treatment.
微小RNA（miRNA）参与多种人类癌症的进展和转移，包括乳腺癌，因为已有强有力的证据表明miRNA可以作为癌基因或肿瘤抑制基因发挥作用。在此，我们发现miR-494在人类乳腺癌标本和乳腺癌细胞系中表达降低。在基底样乳腺癌细胞系MDA-MB-231-LUC-D2H3LN和BT-549中异位表达miR-494可在体外抑制克隆形成能力和与转移相关的特性。此外，miR-494的异位表达在体内可抑制肿瘤起始以及肺转移。进一步研究确定PAK1是miR-494的直接靶基因，它对miR-494的功能有影响。值得注意的是，在人类乳腺癌样本中，PAK1的表达与miR-494的水平呈负相关。此外，重新表达PAK1可部分逆转miR-494介导的乳腺癌细胞增殖和克隆形成抑制以及迁移和侵袭抑制。综上所述，这些发现突出了miR-494在调节乳腺癌进展和转移潜能中的重要作用，并提示miR-494在乳腺癌治疗中的潜在应用。
