Circ_0067835 Knockdown Enhances the Radiosensitivity of Colorectal Cancer by miR-296-5p/IGF1R Axis

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 downregulating 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.

Oncogenic Role of Exosomal Circular and Long Noncoding RNAs in Gastrointestinal Cancers

“…Furthermore, exosomal circ_IFT80 desensitizes recipient cells to radiation [42]. In their studies, circ_0067835 and circ_IFT80 were found to positively regulate the level of insulin-like growth factor 1 receptor (IGF1R) and musashi-1 (MSI1), respectively, by sponging miR-296-5p [37,42] (Figure 2 and Table 1). IGF1R and MSI1 have been investigated to reduce radiosensitivity by activating DNA damage repair [56,57].…”

“…Circ_0067835 is abundant in blood-derived exosomes from patients who received radiotherapy, suggesting an involvement of this circRNA in radiosensitivity modulation. Indeed, it was noticed that radiotherapy-induced apoptosis is increased in cancer cells treated with exosomes derived from circ_0067835-silenced cells [37]. Furthermore, exosomal circ_IFT80 desensitizes recipient cells to radiation [42].…”

Oncogenic Functions and Clinical Significance of Circular RNAs in Colorectal Cancer

“…Wang et al, 2021 [ 222 ] explained the role of hsa_circ_0067835 in the suppression of CRC cell radiosensitivity by miR-296-5p/IGF1R axis.…”

A Preliminary Study on the Pathogenesis of Colorectal Cancer by Constructing a Hsa-circRNA-0067835-miRNA-mRNA Regulatory Network

“…Moreover, it was shown that hsa-circRNA-0067835 (circIFT80) gene knockout can enhance the radiosensitivity of CRC through the miR-296-5p/IGF1R axis. 8 CircIFT80 also promotes the progression of CRC through the miR-1236-3p/ HOXB7 axis. 9 In summary, it shows that circIFT80 plays an important role in the tumor progression of CRC.…”