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Molecular Cancer
Published in: Molecular Cancer 1/2020

Open Access 01-12-2020 | Colorectal Cancer | Research

Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340

Authors: Xiangyu Jian, Han He, Jiehong Zhu, Qi Zhang, Zhongxin Zheng, Xiangjing Liang, Liuyan Chen, Meiling Yang, Kaiyue Peng, Zhaowen Zhang, Tengfei Liu, Yaping Ye, Hongli Jiao, Shuyang Wang, Weijie Zhou, Yanqing Ding, Tingting Li

Published in: Molecular Cancer | Issue 1/2020

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Abstract

Background

Accumulating evidence indicates that circular RNAs (circRNAs) act as microRNA (miRNA) sponges to directly inhibit specific miRNAs and alter their ability to regulate gene expression at the post-transcriptional level; this mechanism is believed to occur in various cancers. However, the expression level, precise function and mechanism of circ_001680 in colorectal carcinoma (CRC) are largely unknown.

Methods

qRT-PCR was used to detect the expression of circ_001680 and miR-340 in human CRC tissues and their matched normal tissues. Bioinformatics analyses and dual-fluorescence reporter assays were used to evaluate whether circ_001680 could bind to miR-340. Circ_001680 overexpression and knockdown cell lines were constructed to investigate the proliferation and migration abilities in vivo and in vitro through function-based experiments, including CCK8, plate clone formation, transwell, and wounding healing assays. The relationships among circ_001680, miR-340 and BMI1 were investigated by bioinformatics analyses, dual-fluorescence reporter system, FISH, RIP and RNA pull down assays. Sphere forming assays and flow cytometry analyses were used to assess the effect of circ_001680 on the stemness characteristics of CRC cells.

Results

Circ_001680 was more highly expressed in of CRC tissue than in matched adjacent normal tissues from the same patients. Circ_001680 was observed to enhance the proliferation and migration capacity of CRC cells. Furthermore, dual-fluorescence reporter assays confirmed that circ_001680 affects the expression of BMI1 by targeting miR-340. More importantly, we also found that circ_001680 could promote the cancer stem cell (CSC) population in CRC and induce irinotecan therapeutic resistance by regulating the miR-340 target gene BMI1.

Conclusions

Our results demonstrated that circ_001680 is a part of a novel strategy to induce chemotherapy resistance in CRC through BMI1 upregulation. Moreover, circ_001680 may be a promising diagnostic and prognostic marker to determine the success of irinotecan-based chemotherapy.
Appendix
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Metadata
Title
Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340
Authors
Xiangyu Jian
Han He
Jiehong Zhu
Qi Zhang
Zhongxin Zheng
Xiangjing Liang
Liuyan Chen
Meiling Yang
Kaiyue Peng
Zhaowen Zhang
Tengfei Liu
Yaping Ye
Hongli Jiao
Shuyang Wang
Weijie Zhou
Yanqing Ding
Tingting Li
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2020
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-020-1134-8

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