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circEIF4G2 通过 miR-218/HOXA1 通路调节宫颈癌的恶性特征。

circEIF4G2 modulates the malignant features of cervical cancer via the miR‑218/HOXA1 pathway.

机构信息

Department of Gynecology, The Second People's Hospital of Wuhu, Wuhu, Anhui 241000, P.R. China.

Department of Geriatrics, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui 241000, P.R. China.

出版信息

Mol Med Rep. 2019 May;19(5):3714-3722. doi: 10.3892/mmr.2019.10032. Epub 2019 Mar 14.

Abstract

Circular RNAs (circRNAs) serve important roles in tumorigenesis and may be used as novel molecular biomarkers for clinical diagnosis. However, the role and molecular mechanisms of circRNAs in cervical cancer (CC) remain unknown. In the present study, circRNA isoform of eukaryotic translation initiation factor 4γ2 (circEIF4G2) was revealed to be significantly upregulated in CC tissues and cell lines. Furthermore, increased expression of circEIF4G2 was associated with poor prognosis in patients with CC. circEIF4G2 knockdown suppressed the malignant features of CC cells, including cell proliferation, colony formation, migration and invasion. Additionally, circEIF4G2 was identified to serve as a sponge for microRNA‑218 (miR‑218), which targeted homeobox A1 (HOXA1). Furthermore, circEIF4G2 may increase the expression levels of HOXA1 by sponging miR‑218. Rescue experiments suggested that transfection with a miR‑218 inhibitor attenuated the inhibitory effects of circEIF4G2 knockdown on cell proliferation, migration and invasion. Furthermore, silencing HOXA1 reversed the effects of the miR‑218 inhibitor on CC cells. Collectively, the present findings suggested that circEIF4G2 promoted cell proliferation and migration via the miR‑218/HOXA1 pathway.

摘要

环状 RNA(circRNAs)在肿瘤发生中发挥重要作用,可能作为临床诊断的新型分子生物标志物。然而,circRNAs 在宫颈癌(CC)中的作用和分子机制尚不清楚。在本研究中,发现真核翻译起始因子 4γ2 的环状 RNA 异构体(circEIF4G2)在 CC 组织和细胞系中显著上调。此外,circEIF4G2 的高表达与 CC 患者的不良预后相关。circEIF4G2 敲低抑制了 CC 细胞的恶性特征,包括细胞增殖、集落形成、迁移和侵袭。此外,circEIF4G2 被鉴定为 microRNA-218(miR-218)的海绵体,miR-218 靶向同源盒 A1(HOXA1)。此外,circEIF4G2 可能通过海绵 miR-218 增加 HOXA1 的表达水平。挽救实验表明,转染 miR-218 抑制剂减弱了 circEIF4G2 敲低对细胞增殖、迁移和侵袭的抑制作用。此外,沉默 HOXA1 逆转了 miR-218 抑制剂对 CC 细胞的影响。综上所述,本研究结果表明,circEIF4G2 通过 miR-218/HOXA1 通路促进细胞增殖和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df07/6471440/4ad935318d51/MMR-19-05-3714-g00.jpg

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