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环状 RNA EPSTI1 通过上调宫颈癌中 MSH2 促进肿瘤进展和顺铂耐药。

circEPSTI1 promotes tumor progression and cisplatin resistance via upregulating MSH2 in cervical cancer.

机构信息

Hengyang Maternal and Child Health Hospital, Hengyang 421001, Hunan Province, China.

Department of Pathology, The First People's Hospital of Changde City, Changde 415000, China.

出版信息

Aging (Albany NY). 2022 Jul 2;14(13):5406-5416. doi: 10.18632/aging.204152.

Abstract

CircRNAs (circRNAs) are a kind of non-coding RNAs which are extensively distributed in tissues. Previous investigations reported that circRNAs harbor indispensable roles in modulating the progress of multiple cancers. Nevertheless, the function along with the molecular mechanism of most circRNAs in cervical cancer progression was still not clear. Herein, we illustrated that circEPSTI1 is a remarkably upregulated circRNA, which we validated in tissues with cervical cancer along with cell lines. The biological role of circEPSTI1 in the advancement of cervical cancer was probed via loss-of function assessments. Silencing circEPSTI1 could diminish the proliferative capacity of the cervical cancer cells to spread. In cervical cancer cells, silencing circEPSTI1 dramatically elevated drug responsivity to cisplatin. Mechanically, RNA immuno-precipitation experiments and dual luciferase enzyme reporter experiments were conducted to reveal the molecular mechanism of circEPSTI1 in cervical cancer. In conclusion, this research premise identified the biological function of circEPSTI1-miR-370-3p-MSH2 axis in cervical cancer progression. Our result is significant for slowing the progress of and overcoming drug resistance of cervical cancer.

摘要

circRNAs(circRNAs)是一种广泛分布于组织中的非编码 RNA。先前的研究报道称,circRNAs 在调节多种癌症的进展中起着不可或缺的作用。然而,大多数 circRNAs 在宫颈癌进展中的功能及其分子机制尚不清楚。本文中,我们表明 circEPSTI1 是一种显著上调的 circRNA,我们在宫颈癌组织和细胞系中验证了这一点。通过功能丧失评估探究了 circEPSTI1 在宫颈癌进展中的作用。沉默 circEPSTI1 可降低宫颈癌细胞的增殖能力和扩散能力。在宫颈癌细胞中,沉默 circEPSTI1 可显著提高顺铂的药物反应性。从机制上讲,进行了 RNA 免疫沉淀实验和双荧光素酶酶报告基因实验,以揭示 circEPSTI1 在宫颈癌中的分子机制。总之,这项研究确定了 circEPSTI1-miR-370-3p-MSH2 轴在宫颈癌进展中的生物学功能。我们的研究结果对减缓宫颈癌的进展和克服宫颈癌的耐药性具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9174/9320557/f3b511f011f4/aging-14-204152-g001.jpg

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