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环状RNA Foxo3通过调控miR-199a-5p/ATP结合盒转运体C亚家族成员1轴促进肝癌阿霉素耐药

CircFoxo3 Promotes Adriamycin Resistance Through Regulation of miR-199a-5p/ATP Binding Cassette Subfamily C Member 1 Axis in Hepatocellular Carcinoma.

作者信息

Huang Wei, Huang Feizhou, Feng Chao

机构信息

Department of Hepatopancreatobiliary Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Jun 8;13:5113-5122. doi: 10.2147/OTT.S243571. eCollection 2020.

DOI:10.2147/OTT.S243571
PMID:32606732
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7292492/
Abstract

INTRODUCTION

Chemotherapy resistance is the main cause of poor prognosis in patients with hepatocellular carcinoma (HCC). Therefore, it is important to understand the molecular mechanism of adriamycin (ADM) resistance in HCC. Increasing evidence indicates that circular RNAs (circRNAs) play a crucial regulatory role in different pathological processes. In the current study, we aimed to investigate the roles and the underlying molecular mechanism of circFoxo3 in ADM-resistant HCC.

MATERIALS AND METHODS

Twenty-five pairs of clinical tumors samples and matched normal tissues were collected from patients with HCC. Gain- and loss-function experiments were performed to investigate the role of circFoxo3 in ADM-resistant cells.

RESULTS

CircFoxo3 expression was increased in ADM-resistant HCC tissues and HCC cell lines and in metastatic tissues compared with non-metastatic tissues. CircFoxo3 knockdown reduces and circFoxo3 overexpression enhances HCC cell invasion and tumor growth. In addition, circFoxo3 interacted with miR-199a-5p and regulated miR-199a-5p expression. Furthermore, ATP Binding Cassette Subfamily C Member 1 (ABCC1) was identified as a new target of miR-199a-5p. CircFoxo3 interacted with miR-199a-5p to positively regulate ABCC1 expression, contributing to epithelial-mesenchymal transition progression.

CONCLUSION

CircFoxo3 knockdown reduces and circFoxo3 overexpression enhances HCC cell invasion and tumor growth through regulation of miR-199a-5p/ABCC1 axis. Our findings reveal that circFoxo3 may be novel biomarkers and therapeutic target for HCC treatment.

摘要

引言

化疗耐药是肝细胞癌（HCC）患者预后不良的主要原因。因此，了解HCC中阿霉素（ADM）耐药的分子机制很重要。越来越多的证据表明，环状RNA（circRNAs）在不同的病理过程中起关键的调节作用。在本研究中，我们旨在探讨circFoxo3在ADM耐药HCC中的作用及潜在分子机制。

材料与方法

收集25对HCC患者的临床肿瘤样本及配对的正常组织。进行功能获得和功能缺失实验，以研究circFoxo3在ADM耐药细胞中的作用。

结果

与非转移组织相比，circFoxo3在ADM耐药HCC组织、HCC细胞系及转移组织中的表达增加。circFoxo3敲低可降低、circFoxo3过表达可增强HCC细胞侵袭和肿瘤生长。此外，circFoxo3与miR-199a-5p相互作用并调节miR-199a-5p表达。此外，ATP结合盒亚家族C成员1（ABCC1）被鉴定为miR-199a-5p的新靶点。circFoxo3与miR-199a-5p相互作用以正向调节ABCC1表达，促进上皮-间质转化进程。

结论

circFoxo3敲低通过调节miR-199a-5p/ABCC1轴降低、circFoxo3过表达增强HCC细胞侵袭和肿瘤生长。我们的研究结果表明，circFoxo3可能是HCC治疗的新型生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5053/7292492/cfa40a35307b/OTT-13-5113-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5053/7292492/4b37bb8b0d2c/OTT-13-5113-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5053/7292492/fd5cda4741c1/OTT-13-5113-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5053/7292492/a12412ddb7e5/OTT-13-5113-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5053/7292492/da8e175aa769/OTT-13-5113-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5053/7292492/cfa40a35307b/OTT-13-5113-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5053/7292492/4b37bb8b0d2c/OTT-13-5113-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5053/7292492/fd5cda4741c1/OTT-13-5113-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5053/7292492/a12412ddb7e5/OTT-13-5113-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5053/7292492/da8e175aa769/OTT-13-5113-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5053/7292492/cfa40a35307b/OTT-13-5113-g0005.jpg

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