Yang Zhaoying, He Miao, Wang Keren, Sun Guang, Tang Lu, Xu Zheli
Department of Breast Surgery, China-Japan Union Hospital of Jilin University Changchun, Jilin, China ; Breast Disease Research Institute of Jilin Province Changchun, Jilin, China.
Department of Anesthesiology, Second Hospital of Jilin University Changchun, Jilin, China.
Int J Clin Exp Pathol. 2014 Oct 15;7(11):7563-70. eCollection 2014.
Breast cancer is still a leading cause of cancer deaths in women. Despite improvements in therapeutic approaches in local control, metastatic relapse is almost always incurable, underlining the importance to better understand the biological bases that contribute to disease progression. In this study, we demonstrated that miR-193b was significantly down-regulated in two primary human breast cancer cell lines (MDA-MB-231 and MCF-7). Reconstitution of miR-193b expression resulted in decreasing cell proliferation, clonogenicity, migration and invasion. By using in silico prediction algorithms approach for target identification, we identified DNAJC13 (HPS40) and RAB22A to be direct targets of miR-193b. Concordantly, Re-expression of miR-193b decreased DNAJC13 (HPS40) and RAB22A expression. Luciferase reporter assays confirmed the direct interaction of miR-193b with both DNAJC13 (HPS40) and RAB22A. Our findings have demonstrated that miR-193b as a novel tumor suppressor plays an important role in breast cancer progression, understanding the mechanisms could account for the aggressive behaviour of breast cancer.
乳腺癌仍然是女性癌症死亡的主要原因。尽管局部控制的治疗方法有所改进,但转移性复发几乎总是无法治愈的,这凸显了更好地理解导致疾病进展的生物学基础的重要性。在本研究中,我们证明miR-193b在两种原发性人乳腺癌细胞系(MDA-MB-231和MCF-7)中显著下调。miR-193b表达的重建导致细胞增殖、克隆形成、迁移和侵袭减少。通过使用计算机预测算法方法进行靶点鉴定,我们确定DNAJC13(HPS40)和RAB22A是miR-193b的直接靶点。一致地,miR-193b的重新表达降低了DNAJC13(HPS40)和RAB22A的表达。荧光素酶报告基因测定证实了miR-193b与DNAJC13(HPS40)和RAB22A的直接相互作用。我们的研究结果表明,miR-193b作为一种新型肿瘤抑制因子在乳腺癌进展中起重要作用,了解其机制有助于解释乳腺癌的侵袭性。