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环状RNA PVT1通过充当miR-204-5p的竞争性内源性RNA促进乳腺癌细胞的侵袭和上皮-间质转化。

Circular RNA PVT1 promotes the invasion and epithelial-mesenchymal transition of breast cancer cells through serving as a competing endogenous RNA for miR-204-5p.

作者信息

Bian Qingzhao

机构信息

First Department of Oncology, Cangzhou Central Hospital of Hebei Province, Cangzhou 061001, People's Republic of China.

出版信息

Onco Targets Ther. 2019 Dec 31;12:11817-11826. doi: 10.2147/OTT.S180850. eCollection 2019.

DOI:10.2147/OTT.S180850
PMID:32982273
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7502987/
Abstract

PURPOSE

Circular RNAs (circRNAs) are a class of covalently closed circular RNA transcripts and have been found to regulate the progression of human malignancies. The objective of this study was to identify the functions of circRNAs in breast cancer (BCa).

PATIENTS AND METHODS

BCa and adjacent non-cancerous tissues were collected from 99 patients. Kaplan-Meier analysis was used to analyze the relationship between circPVT1 and prognosis. CircPVT1 expression levels in BCa tissues and cell lines were detected via PCR. Transfection technology was used to silence circPVT1 and overexpress miR-204-5p. Cell biological behavior was analyzed, and epithelial-mesenchymal transition (EMT) related proteins were detected by Western blot. In vivo experiments were performed with the subcutaneous xenograft tumor model.

RESULTS

CircPVT1 was markedly overexpressed in BCa tissues and cell lines. Higher expression of circPVT1 was correlated with poor prognosis of BCa patients. Knockdown circPVT1 significantly suppressed the proliferation, migration and invasion of BCa cells invitro, and suppressed BCa tumor growth invivo. CircPVT1 knockdown upregulated E-cadherin and downregulated N-cadherin, Vimentin, Slug and Twist in BCa cells. Moreover, circPVT1 could serve as a competing endogenous RNA (ceRNA) for miR-204-5p, and restoration of miR-204-5p abrogated the oncogenic role of circPVT1 in BCa cells.

CONCLUSION

CircPVT1 as a potentially valuable biomarker for BCa diagnosis and therapeutic target for BCa treatment. CircPVT1 might promote the invasion and EMT of BCa cells by serving as aceRNA for miR-204-5p.

摘要

目的

环状RNA（circRNAs）是一类共价闭合的环状RNA转录本，已发现其可调节人类恶性肿瘤的进展。本研究的目的是确定circRNAs在乳腺癌（BCa）中的功能。

患者和方法

收集99例患者的BCa组织及癌旁非癌组织。采用Kaplan-Meier分析来分析circPVT1与预后的关系。通过PCR检测BCa组织和细胞系中circPVT1的表达水平。利用转染技术沉默circPVT1并过表达miR-204-5p。分析细胞生物学行为，并通过蛋白质印迹法检测上皮-间质转化（EMT）相关蛋白。采用皮下异种移植瘤模型进行体内实验。

结果

circPVT1在BCa组织和细胞系中显著过表达。circPVT1的高表达与BCa患者的不良预后相关。敲低circPVT1可显著抑制BCa细胞的体外增殖、迁移和侵袭，并抑制体内BCa肿瘤生长。敲低circPVT1可上调BCa细胞中E-钙黏蛋白的表达，并下调N-钙黏蛋白、波形蛋白、Slug和Twist的表达。此外，circPVT1可作为miR-204-5p的竞争性内源性RNA（ceRNA），恢复miR-204-5p可消除circPVT1在BCa细胞中的致癌作用。

结论

circPVT1作为BCa诊断的潜在有价值生物标志物及BCa治疗的靶点。circPVT1可能通过作为miR-204-5p的ceRNA促进BCa细胞的侵袭和EMT。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/116b/7502987/4e17c78c3453/OTT-12-11817-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/116b/7502987/ee1b07aab602/OTT-12-11817-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/116b/7502987/054795c87718/OTT-12-11817-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/116b/7502987/30b50eb8a313/OTT-12-11817-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/116b/7502987/8ad654bf673a/OTT-12-11817-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/116b/7502987/d1ca2bceed22/OTT-12-11817-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/116b/7502987/629ca1a6c4ba/OTT-12-11817-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/116b/7502987/4e17c78c3453/OTT-12-11817-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/116b/7502987/ee1b07aab602/OTT-12-11817-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/116b/7502987/054795c87718/OTT-12-11817-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/116b/7502987/30b50eb8a313/OTT-12-11817-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/116b/7502987/8ad654bf673a/OTT-12-11817-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/116b/7502987/d1ca2bceed22/OTT-12-11817-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/116b/7502987/629ca1a6c4ba/OTT-12-11817-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/116b/7502987/4e17c78c3453/OTT-12-11817-g0007.jpg

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