Department of Medical Oncology, Shanghai Changzheng Hospital, Affiliated to The Second Military Medical University, Shanghai 200070, China.
FEBS Lett. 2013 May 2;587(9):1434-9. doi: 10.1016/j.febslet.2013.03.023. Epub 2013 Mar 20.
Previous cDNA microarrays indicated that CLDN1 (claudin-1) is an important gene for ovarian cancer-initiating cell (OCIC) invasion and adhesion. Here, we show that the downregulation of miR-155 in OCICs correlates with CLDN1 overexpression and the suppression of OCIC invasion. Luciferase assays indicate that miR-155 targets CLDN1 mRNA on the 3' UTR. CLDN1 mRNA and claudin-1 protein expression were significantly decreased in miR-155-OCICs. Proliferation assays and Transwell migration assays show that miR-155 significantly suppresses the proliferative and invasive capacity of OCICs. Furthermore, miR-155 suppresses the growth of OCIC xenograft tumors. Thus, overexpression of miR-155 may prevent tumorigenesis in human ovarian cancer through downregulation of CLDN1.
先前的 cDNA 微阵列表明，CLDN1（紧密连接蛋白 1）是卵巢癌起始细胞（OCIC）侵袭和黏附的重要基因。在这里，我们表明 OCIC 中 miR-155 的下调与 CLDN1 的过表达和 OCIC 侵袭的抑制相关。荧光素酶报告基因实验表明，miR-155 靶向 CLDN1 mRNA 的 3'UTR。miR-155-OCIC 中 CLDN1 mRNA 和紧密连接蛋白 1 蛋白的表达显著降低。增殖实验和 Transwell 迁移实验表明，miR-155 显著抑制 OCIC 的增殖和侵袭能力。此外，miR-155 抑制 OCIC 异种移植肿瘤的生长。因此，miR-155 的过表达可能通过下调 CLDN1 来防止人类卵巢癌的发生。
