Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340
Authors: Liuyan Chen
Tingting Li
Zhongxin Zheng
Kaiyue Peng
Han He
Weijie Zhou
Tengfei Liu
Hongli Jiao
Zhaowen Zhang
Xiangjing Liang
Qi Zhang
Yanqing Ding
Shuyang Wang
Xiangyu Jian
Jiehong Zhu
Meiling Yang
Yaping Ye
Journal: Molecular Cancer (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: BMI1; Chemotherapy resistance; Has-circ_001680; Irinotecan; Stem cell
Affiliations: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China., Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China., Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China., Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. ., Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China. .

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. 

Retracted: No

PubPeer comments:
 Figure 2H * Blue boxes: In the  Scramble row, the 48h and 96h panels appear to look very similar. Since there are 2 different time points of the same cells some similarity is expected, but these 2 panels appear to look more similar than expected, almost as two different exposures of the same sample.  , 
 Thanks very much for you comment. I am apologize for the mistake. The following is the picture of first submission on August 12,2019 and we have submission record. We put this result in supplemental figure2. Reviewer advice we put this result in figure 2. We made the mistake when we rearranged these results. I will contact the editor to solve the problem immediately. Thanks again for your kindly remind. If you have any questions, please donu2019t hesitate to let us know.! ,