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miR-335 通过靶向 Bcl-w 成为卵巢癌的侵袭抑制基因。

miR-335 represents an invasion suppressor gene in ovarian cancer by targeting Bcl-w.

机构信息

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China.

出版信息

Oncol Rep. 2013 Aug;30(2):701-6. doi: 10.3892/or.2013.2482. Epub 2013 May 23.

DOI:10.3892/or.2013.2482
PMID:23708561
Abstract

microRNAs (miRNAs) are a class of non-coding small RNAs that bind to target mRNAs, usually resulting in post-transcriptional repression by translational inhibition or target degradation. mRNAs can function as tumor suppressors or oncogenes (also referred to as oncomirs) in human tumors. Although aberrant expression of miR-335 has been reported in ovarian cancer, whether it is an active participant or a mere bystander remains unknown. To clarify its role in ovarian carcinogenesis, we first examined the relative expression of miR-335 in 17 normal ovarian tissues and 4 ovarian cancer cell lines using qPCR. We found that miR-335 was downregulated in the ovarian cancer cell lines relative to normal ovarian epithelium tissues. In vitro, overexpression of miR-335 suppressed cell migration and invasion and resulted in depolymerization of F-actin in ovarian cancer cell lines, but exhibited a negligible effect on cell proliferation. B-cell CLL/lymphoma 2 like 2 (Bcl-w or BCL2L2), a pro-survival member of the Bcl-2 protein family, was identified as a potential target of miR-335 according to the results of bioinformatic analysis, and the expression of Bcl-w and its effector matrix metalloproteinase-2 (MMP‑2) was downregulated after transfection with miR-335 mimics. In addition, ectopic Bcl-w could almost fully nullify the effect of miR-335 overexpression on ovarian cancer cell migration and invasion. These findings indicate that the tiny genome product, miR-335, whose lack of expression brings about the abnormal accumulation of Bcl-w and subsequent unchecked cell invasion in ovarian cancer, may help us to understand one of the many steps ovarian cells take on their way toward the acquisition of malignant phenotypes and miR-335 may be a promising predictor of survival.

摘要

微小 RNA(miRNA)是一类非编码的小 RNA,可与靶 mRNA 结合,通常通过翻译抑制或靶标降解导致转录后抑制。mRNA 在人类肿瘤中可以作为肿瘤抑制因子或癌基因(也称为癌 microRNA)发挥作用。尽管已经报道 miR-335 在卵巢癌中表达异常,但它是积极参与者还是仅仅是旁观者尚不清楚。为了阐明其在卵巢癌发生中的作用,我们首先使用 qPCR 检查了 17 个正常卵巢组织和 4 个卵巢癌细胞系中 miR-335 的相对表达。我们发现,与正常卵巢上皮组织相比,miR-335 在卵巢癌细胞系中下调。在体外,miR-335 的过表达抑制了卵巢癌细胞系的迁移和侵袭,并导致 F-肌动蛋白解聚,但对细胞增殖几乎没有影响。B 细胞 CLL/淋巴瘤 2 样 2(Bcl-w 或 BCL2L2)是 Bcl-2 蛋白家族的一种生存促进成员,根据生物信息学分析的结果,被鉴定为 miR-335 的潜在靶标,并且 Bcl-w 及其效应物基质金属蛋白酶-2(MMP-2)的表达在转染 miR-335 模拟物后下调。此外,外源性 Bcl-w 几乎可以完全消除 miR-335 过表达对卵巢癌细胞迁移和侵袭的影响。这些发现表明,微小的基因组产物 miR-335 的缺乏导致 Bcl-w 的异常积累,并随后在卵巢癌中不受控制的细胞侵袭,这可能有助于我们理解卵巢细胞获得恶性表型的许多步骤之一,并且 miR-335 可能是一个有前途的生存预测因子。

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