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环状FAM114A2通过miR-222-3p/P27和miR-146a-5p/P21级联反应促进尿路上皮癌对顺铂的敏感性。

CircFAM114A2 Promotes Cisplatin Sensitivity miR-222-3p/P27 and miR-146a-5p/P21 Cascades in Urothelial Carcinoma.

作者信息

Lv Jiancheng, Zhou Zijian, Wang Jingzi, Yang Xiao, Yu Hao, Han Jie, Feng Dexiang, Yuan Baorui, Wu Qikai, Li Pengchao, Lu Qiang, Yang Haiwei

机构信息

Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Front Oncol. 2021 Oct 14;11:659166. doi: 10.3389/fonc.2021.659166. eCollection 2021.

DOI:10.3389/fonc.2021.659166
PMID:34722233
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8551855/
Abstract

INTRODUCTION

Circular RNAs (circRNAs) are non-coding RNAs that have the structure of a covalently closed loop. Increasing data have proven that circRNAs can influence the progression and chemotherapy sensitivity of tumors. Therefore, the underlying function and mechanisms of more circRNAs in progression and chemotherapy resistance are important.

METHODS

We conducted RNA sequencing on five pairs of urothelial carcinoma samples and screened for circRNAs. CircFAM114A2 was found to be low expressed in urothelial carcinoma. The functions of circFAM114A2 in urothelial carcinoma were explored by cell cycle assay, IC determination assay, cell proliferation assay, apoptosis assay, and tumorigenesis assay.

RESULTS

We discovered that the levels of circFAM114A2 were decreased in urothelial carcinoma cell lines and tissues. According to follow-up data, urothelial carcinoma patients with higher circFAM114A2 expression had better survival. Importantly, the levels of circFAM114A2 were associated with the histological grade of urothelial carcinoma. CircFAM114A2 could inhibit cell proliferation and block more urothelial carcinoma cells in the G1 phase and then increase the sensitivity of urothelial carcinoma to cisplatin chemotherapy. Mechanistically, circFAM114A2 directly sponged miR-222-3p/miR-146a-5p and subsequently influenced the expressions of the downstream target genes /, which, in turn, inhibited the progression of urothelial carcinoma and increased the sensitivity of cancer cells to cisplatin chemotherapy.

CONCLUSION

CircFAM114A2 could inhibit progression and promote cisplatin sensitivity in urothelial carcinoma through novel circFAM114A2/miR-222-3p/P27 and circFAM114A2/miR-146a-5p/P21 pathways. CircFAM1142 has therefore great potential as a prognostic biomarker and therapeutic target for urothelial carcinoma.

摘要

引言

环状RNA（circRNAs）是具有共价闭合环状结构的非编码RNA。越来越多的数据证明，circRNAs可影响肿瘤的进展和化疗敏感性。因此，更多circRNAs在肿瘤进展和化疗耐药中的潜在功能及机制具有重要意义。

方法

我们对五对尿路上皮癌样本进行了RNA测序，并筛选circRNAs。发现circFAM114A2在尿路上皮癌中低表达。通过细胞周期检测、IC测定、细胞增殖检测、凋亡检测和肿瘤发生检测，探索circFAM114A2在尿路上皮癌中的功能。

结果

我们发现circFAM114A2在尿路上皮癌细胞系和组织中的水平降低。根据随访数据，circFAM114A2表达较高的尿路上皮癌患者生存情况更好。重要的是，circFAM114A2的水平与尿路上皮癌的组织学分级相关。circFAM114A2可抑制细胞增殖，并使更多尿路上皮癌细胞停滞于G1期，进而增加尿路上皮癌对顺铂化疗的敏感性。机制上，circFAM114A2直接吸附miR-222-3p/miR-146a-5p，随后影响下游靶基因的表达，进而抑制尿路上皮癌的进展并增加癌细胞对顺铂化疗的敏感性。

结论

circFAM114A2可通过新的circFAM114A2/miR-222-3p/P27和circFAM114A2/miR-146a-5p/P21途径抑制尿路上皮癌的进展并提高顺铂敏感性。因此，circFAM1142作为尿路上皮癌的预后生物标志物和治疗靶点具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386c/8551855/9c4fec321757/fonc-11-659166-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386c/8551855/d6b191d44b91/fonc-11-659166-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386c/8551855/226b6b407907/fonc-11-659166-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386c/8551855/0db18712711b/fonc-11-659166-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386c/8551855/c8b13e0fac3c/fonc-11-659166-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386c/8551855/ebad96cda416/fonc-11-659166-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386c/8551855/8c6590f9a7be/fonc-11-659166-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386c/8551855/9c4fec321757/fonc-11-659166-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386c/8551855/d6b191d44b91/fonc-11-659166-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386c/8551855/226b6b407907/fonc-11-659166-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386c/8551855/0db18712711b/fonc-11-659166-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386c/8551855/c8b13e0fac3c/fonc-11-659166-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386c/8551855/ebad96cda416/fonc-11-659166-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386c/8551855/8c6590f9a7be/fonc-11-659166-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386c/8551855/9c4fec321757/fonc-11-659166-g007.jpg

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