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miR-181a-5p 通过调节肌醇多磷酸-5-磷酸酶 A(INPP5A)促进宫颈癌细胞的增殖、侵袭,抑制其凋亡。

miR-181a-5p Promotes Proliferation and Invasion and Inhibits Apoptosis of Cervical Cancer Cells via Regulating Inositol Polyphosphate-5-Phosphatase A (INPP5A).

机构信息

Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, P.R. China.

Department of Anesthesia, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, P.R. China.

出版信息

Oncol Res. 2018 Jun 11;26(5):703-712. doi: 10.3727/096504017X14982569377511. Epub 2017 Jun 23.

Abstract

Expression of miR-181a-5p associates with the proliferation and progression of cancer cells via its targets. This study was designed to investigate the effect of miR-181a-5p and its target inositol polyphosphate-5-phosphatase A (INPP5A) on the progression of cervical cancers. Upregulation of miR-181a-5p was revealed in the cervical cancer cell lines HeLa and SiHa in comparison with a normal cervical epithelium cell line End1/E6E7 (p < 0.001). The inhibition and upregulation of miR-181a-5p in cervical cancer cell lines significantly reduced or increased cell proliferation and invasion capacity, accompanied with enhanced or reduced apoptosis (p < 0.05). Moreover, INPP5A overexpression significantly inhibited cell proliferation and invasion capacity and enhanced cell apoptosis. The target relationship of miR-181a-5p to INPP5A was demonstrated by both the results of the Dual-Luciferase Reporter Assay and the fact that the miR-181a-5p mimic attenuated INPP5A's effect on cell proliferation, invasion, and apoptosis. To sum up, the overexpression of miR-181a-5p enhanced cell proliferation and invasion and inhibited apoptosis of cervical cancer cells by negatively targeting INPP5A. Therefore, inhibition of miR-181a-5p might benefit the inhibition of cervical cancer cell invasion.

摘要

miR-181a-5p 的表达通过其靶标与癌细胞的增殖和进展相关。本研究旨在探讨 miR-181a-5p 及其靶标肌醇多磷酸-5-磷酸酶 A(INPP5A)对宫颈癌进展的影响。与正常宫颈上皮细胞系 End1/E6E7 相比,在宫颈癌细胞系 HeLa 和 SiHa 中发现 miR-181a-5p 上调(p<0.001)。miR-181a-5p 在宫颈癌细胞系中的抑制和上调显著降低或增加了细胞增殖和侵袭能力,并伴随着增强或降低的细胞凋亡(p<0.05)。此外,INPP5A 的过表达显著抑制了细胞增殖和侵袭能力,并增强了细胞凋亡。miR-181a-5p 对 INPP5A 的靶标关系通过双荧光素酶报告基因检测和 miR-181a-5p 模拟物减弱 INPP5A 对细胞增殖、侵袭和凋亡的影响这两个事实得到证明。总之,miR-181a-5p 的过表达通过负向靶向 INPP5A 增强了宫颈癌细胞的增殖、侵袭和抑制凋亡。因此,抑制 miR-181a-5p 可能有益于抑制宫颈癌细胞的侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d19/7844749/ca64996e1249/OR-26-703-g001.jpg

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