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长链非编码核斑蛋白组装转录本 1 通过隔离 microRNA-101 作为宫颈癌的预后生物标志物并增加细胞生长和侵袭。

Long non‑coding nuclear paraspeckle assembly transcript 1 acts as prognosis biomarker and increases cell growth and invasion in cervical cancer by sequestering microRNA‑101.

机构信息

Department of Obstetrics and Gynecology, Xidian Group Hospital, Xi'an, Shaanxi 710077, P.R. China.

Department of Obstetrics and Gynecology, Xianyang Caihong Hospital, Xianyang, Shaanxi 712021, P.R. China.

出版信息

Mol Med Rep. 2018 Feb;17(2):2771-2777. doi: 10.3892/mmr.2017.8186. Epub 2017 Nov 29.

DOI:10.3892/mmr.2017.8186
PMID:29207151
Abstract

Emerging studies have focused on the essential role of long non‑coding RNAs (lncRNAs) in cervical carcinogenesis. A recent study has indicated that nuclear paraspeckle assembly transcript 1 (NEAT1) is highly expressed in the human cervical tissue. However, whether NEAT1 is involved in cervical cancer remains to be elucidated. Reverse transcription‑quantitative polymerase chain reaction results demonstrated that the expression of NEAT1 was higher in cervical cancer cells/tissues compared with that in normal human keratinocytes/tissues. Patients with higher NEAT1 level had poorer clinical characteristics and a shorter survival time compared with those that exhibited lower NEAT1 expression levels. In vitro, flow cytometery analysis revealed that transfection with NEAT1 small interfering RNA retarded cervical cancer cell (Caski and HeLa) growth by decreasing the percentage of S phase in the cell cycle and inducing cell apoptosis. In addition, the colony formation assay, wound healing assay and matrigel invasion assay results indicated that downregulation of NEAT1 inhibited colony formation, cell migration and invasion. Further investigation using the luciferase reporter assay revealed that the expression of mircoRNA‑101 (miR‑101) target gene Fos was positively associated with NEAT1 expression due to NEAT1‑competitive molecular sequestering of miR‑101 via base pairing. Furthermore, reduction of miR‑101 expression by inhibitor transfection reversed the effect of NEAT1 siRNA on cervical cancer cells. To conclude, the present data indicated that NEAT1 promoted cervical cancer progression by targeting miR‑101.

摘要

新兴研究集中于长非编码 RNA(lncRNA)在宫颈癌发生中的重要作用。最近的一项研究表明,核斑蛋白组装转录本 1(NEAT1)在人宫颈组织中高表达。然而,NEAT1 是否参与宫颈癌仍有待阐明。逆转录-定量聚合酶链反应结果表明,与正常人类角质形成细胞/组织相比,宫颈癌细胞/组织中 NEAT1 的表达更高。与表达水平较低的患者相比,NEAT1 水平较高的患者具有较差的临床特征和较短的生存时间。在体外,流式细胞术分析显示,转染 NEAT1 小干扰 RNA 通过降低细胞周期 S 期的百分比和诱导细胞凋亡来抑制宫颈癌细胞(Caski 和 HeLa)的生长。此外,集落形成实验、划痕愈合实验和基质胶侵袭实验结果表明,下调 NEAT1 抑制集落形成、细胞迁移和侵袭。进一步使用荧光素酶报告基因实验进行的研究表明,由于 NEAT1 通过碱基配对竞争性分子隔离 miR-101,miR-101 靶基因 Fos 的表达与 NEAT1 表达呈正相关。此外,通过抑制剂转染降低 miR-101 的表达逆转了 NEAT1 siRNA 对宫颈癌细胞的作用。总之,本研究数据表明,NEAT1 通过靶向 miR-101 促进宫颈癌的进展。

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