Circ_0067835 Knockdown Enhances the Radiosensitivity of Colorectal Cancer by miR-296-5p/IGF1R Axis
Authors: Yongmin Sun
Yang Yang
Peng Wang
Yanzhao Chen
Hui Liu
Journal: OncoTargets and Therapy (2021)
Discipline: CLINICAL MEDICINE
Keywords: IGF1R; circ_0067835; colorectal cancer; exosomes; miR-296-5p.
Affiliations: Department of Nuclear Medicine, Henan Provincial People's Hospital, Zhengzhou, Henan, People's Republic of China., Department of Nuclear Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

Abstract:  Background: Colorectal cancer (CRC) is one of the most common malignant cancers globally. Circular RNAs (circRNAs) have been implicated in the development of CRC. In this paper, we set to explore the precise action of circ_0067835 in CRC progression and radioresistance. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate the expression of circ_0067835, microRNA-296-5p (miR-296-5p) and insulin-like growth factor 1 receptor (IGF1R). Western blot was used to measure the level of IGF1R protein. Cell proliferation, cell cycle distribution and apoptosis were determined by Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry and caspase-3 activity assays, respectively. The direct relationship between miR-296-5p and circ_0067835 or IGF1R was verified by dual-luciferase reporter assays. Additionally, in vivo assays were applied to confirm the role of circ_0067835 in vivo. Results: Exosomal circ_0067835 was upregulated in the serum of CRC patients after radiotherapy. Exosome-mediated circ_0067835 knockdown repressed cell proliferation, cell cycle progression, and enhanced cell apoptosis and radiosensitivity in vitro. Circ_0067835 sponged miR-296-5p to regulate IGF1R expression in CRC cells. Moreover, the knockdown of circ_0067835 regulated CRC cell behaviors by up-regulating miR-296-5p and down-regulating IGF1R in vitro. Furthermore, circ_0067835 knockdown diminished tumor growth and promoted cell radiosensitivity in vivo. Conclusion: Circ_0067835 knockdown suppressed CRC progression and enhanced CRC cell radiosensitivity partially by the miR-296-5p/IGF1R axis. The findings established a rationale that targeting circ_0067835 might be a promising point for improving CRC treatment. 

Retracted: No

PubPeer comments:
 Figure 7A and 7B should represent blots of different proteins, but they are much more similar than expected. Could the authors check it, please? ![file] , 
 Answer from the authors: First of all, we appreciate your careful observation and relevant comment, regarding our manuscript published in Cellular Physiology and Biochemistry 2019;53:587-605. In fact, there was a mistake during the final preparation of Figure 7B before their submission on August 25, 2019 to the Editor-in-Chief. We repeated in Figure 7B the representative blot of Figure 7A, which corresponds to Angiotensin II type 1 receptor (AT1R). We corrected the figure, which now shows a proper representative blot of Angiotensinogen Angiotensin II (AGT Ang II) (see below). We apologize for this mistake. We will immediately communicate the mistake to the Editor of Cellular Physiology and Biochemistry, requesting publication of an Erratum.![file] ![file] , 
 Answer from the authors: First of all, we appreciate your careful observation and relevant comment, regarding our manuscript published in Cellular Physiology and Biochemistry 2019;53:587-605. In fact, there was a mistake during the final preparation of Figure 7B before their submission on August 25, 2019 to the Editor-in-Chief. We repeated in Figure 7B the representative blot of Figure 7A, which corresponds to Angiotensin II type 1 receptor (AT1R). We corrected the figure, which now shows a proper representative blot of Angiotensinogen Angiotensin II (AGT Ang II) (see below). We apologize for this mistake. We will immediately communicate the mistake to the Editor of Cellular Physiology and Biochemistry, requesting publication of an Erratum.![file] ![file] ,