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- Title
Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340.
- Authors
Jian, Xiangyu; He, Han; Zhu, Jiehong; Zhang, Qi; Zheng, Zhongxin; Liang, Xiangjing; Chen, Liuyan; Yang, Meiling; Peng, Kaiyue; Zhang, Zhaowen; Liu, Tengfei; Ye, Yaping; Jiao, Hongli; Wang, Shuyang; Zhou, Weijie; Ding, Yanqing; Li, Tingting
- 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.
- Subjects
DRUG resistance in cancer cells; CIRCULAR RNA; CANCER stem cells; GENE expression; FLOW cytometry
- Publication
Molecular Cancer, 2020, Vol 19, Issue 1, p1
- ISSN
1476-4598
- Publication type
Article
- DOI
10.1186/s12943-020-1134-8