miR-506 suppresses cervical cancer cell proliferation both in vitro and in vivo

miR-506 suppresses cervical cancer cell proliferation both in vitro and in vivo
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DOI:
10.4149/neo_2018_170112n25
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发表时间:
2018-01-01
期刊:
影响因子:
3
通讯作者:
Song, M.
Song, M.
中科院分区:
医学4区
文献类型:
--
作者:
Gong, M.;Chen, C.;Song, M.

文献摘要

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宫颈癌是世界范围内最常见的妇科恶性肿瘤之一。近年来,越来越多的证据表明miR-506的异常表达与多种肿瘤相关。本研究的目的是评估miR-506在CC中的潜在作用,并验证其对ABCC 4的调节作用。采用实时荧光定量PCR检测宫颈癌组织、HeLa细胞和C33 A细胞中miR-506的表达。采用MTT法和动物实验检测miR-506对宫颈癌细胞增殖的影响。荧光素酶报告基因和蛋白质印迹法证实miR-506可以调控ABCC 4。我们发现,miR-506在人CC细胞系(HeLa和C33 A)和临床CC标本中的表达显著低于匹配的细胞系和癌旁正常组织,而ABCC 4在肿瘤组织中的表达水平高于癌旁正常组织。上调miR-506的表达可抑制CC细胞在体内外的增殖。此外,ABCC 4被鉴定为miR-506的直接靶点,并且还观察到它们之间的反向关系。总之,我们的研究结果表明,miR-506在抑制CC细胞增殖中具有重要作用,并通过直接靶向其3 '-UTR抑制ABCC 4的表达。miR-506可能代表了microRNA介导的CC细胞增殖抑制的新治疗靶点,但miR-506/ABCC 4轴在CC进展中的作用需要进一步研究。
Cervical cancer (CC) is one of the most common gynecological malignancies in women worldwide. Recently, increasing evidence indicates aberrant expression of miR-506, which was reported to be associated with a variety of tumors. The aim of this study was to evaluate the potential role of miR-506 in CC and to verify its effect on the regulation of ABCC4. The expression of miR-506 in cervical cancer tissues, HeLa and C33A cell lines was examined using quantitative Real-time PCR. MTT assay and animals studies were used to examine the effects of miR-506 on cervical cancer proliferation. Luciferase reporter and western blot were used to confirm that 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 to matched cell lines and adjacent normal tissues, while the expression level of ABCC4 was higher in tumor tissues than in the 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 findings suggest that miR-506 has 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.