Department of Obstetrics and Gynecology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Neoplasma. 2018 Mar 14;65(3):331-338. doi: 10.4149/neo_2018_170112N25.
Cervical cancer (CC) is one of the most common gynecological malignancies in women worldwide. Recently increasing evidences indicate aberrant expression of miR-506 was reported to be associated with a variety of tumors. The aimof this study was to evaluate the potential role of miR-506 in CC and verify its effect on the regulation of ABCC4. The expression of miR-506 in cervical cancer tissues and HeLa and C33A cell lines was examined using quantitative Real-time PCR. MTT assay and animals studies were use to examine the effects of miR-506 on cervical cancer proliferation. Luciferase reporter and western blot were used to confirm miR-506 could regulate ABCC4. We found that miR-506 was significantly downregulated in human CC cell lines (HeLa and C33A) and clinical CC specimens as compared with matched cell lines and adjacent normal tissues, while the expression level of ABCC4 was higher in tumor tissues than it in adjacent normal tissues. We also revealed that up-regulated expression of miR-506 could inhibit CC cells proliferation both in vitro and in vivo. Moreover, ABCC4 was identified as a direct target of miR-506 and the inverse relationship between them was also observed. In summary, our finding suggests that miR-506 acts an important role in suppressing CC cell proliferation and suppresses the expression of ABCC4 by directly targeting its 3'-UTR. miR-506 may represent a novel therapeutic target of microRNA-mediated suppression of cell proliferation in CC, but the role of the miR-506/ABCC4 axis in CC progression needs further study.
宫颈癌(CC)是全球女性最常见的妇科恶性肿瘤之一。最近越来越多的证据表明,miR-506 的异常表达与多种肿瘤有关。本研究旨在评估 miR-506 在 CC 中的潜在作用,并验证其对 ABCC4 调节的影响。采用定量实时 PCR 检测宫颈癌组织及 HeLa 和 C33A 细胞系中 miR-506 的表达。MTT 试验和动物研究用于检测 miR-506 对宫颈癌增殖的影响。荧光素酶报告和 Western blot 用于证实 miR-506 可调节 ABCC4。结果发现,与匹配的细胞系和相邻正常组织相比,miR-506 在人宫颈癌细胞系(HeLa 和 C33A)和临床 CC 标本中表达明显下调,而 ABCC4 的表达水平在肿瘤组织中高于相邻正常组织。还揭示了上调 miR-506 的表达可抑制体外和体内 CC 细胞的增殖。此外,鉴定出 ABCC4 是 miR-506 的直接靶标,并且它们之间存在相反的关系。综上所述,我们的研究结果表明,miR-506 在抑制 CC 细胞增殖中起重要作用,并通过直接靶向其 3'-UTR 抑制 ABCC4 的表达。miR-506 可能代表了 miRNA 抑制 CC 细胞增殖的新型治疗靶点,但 miR-506/ABCC4 轴在 CC 进展中的作用仍需要进一步研究。