Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis

Ximin Wang; Dongxu Zheng; Changting Wang; Wanhua Chen

doi:10.1515/med-2023-0678

Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis

Open Med (Wars). 2023 May 9;18(1):20230678. doi: 10.1515/med-2023-0678. eCollection 2023.

Authors

Ximin Wang¹, Dongxu Zheng², Changting Wang³, Wanhua Chen¹

Affiliations

¹ Department of Clinical Laboratory, The Second Affiliated Hospital of Fujian Medical University, Licheng, Quanzhou, Fujian, 362000, P. R. China.
² Department of Clinical Laboratory, The Second Affiliated Hospital of Fujian Medical University, 34 Zhongshan North Road, Licheng, Quanzhou, Fujian, 362000, P. R. China.
³ Department of General Surgery, The Second Affiliated Hospital of Fujian Medical University, Licheng, Quanzhou, Fujian, 362000, P. R. China.

Abstract

Radiotherapy resistance is a challenge for colorectal cancer (CRC) treatment. Circular RNAs (circRNAs) play vital roles in the occurrence and development of CRC. This study aimed to investigate the role of circ_0005615 in regulating the radiosensitivity of CRC. The levels of circ_0005615, microRNA-665 (miR-665), and notch receptor 1 (NOTCH1) were detected by quantitative real-time PCR or western blot. The radiosensitivity of CRC cells was assessed by colony formation assay. Cell viability, apoptosis, and colony formation were assessed by Cell Counting Kit-8 assay, flow cytometry, and colony formation assay. Cell migration and invasion were confirmed by transwell assay and scratch assay. The binding relationship between miR-665 and circ_0005615 or NOTCH1 was verified by dual-luciferase reporter assay. Xenograft assay was used to test the effect of circ_0005615 on radiosensitivity in vivo. circ_0005615 and NOTCH1 were up-regulated, and miR-665 was down-regulated in CRC tissues and cells. Radiation decreased circ_0005615 and NOTCH1 levels and increased miR-665 level. Knockdown of circ_0005615 enhanced radiosensitivity of CRC cells. Moreover, circ_0005615 sponged miR-665 to regulate the radioresistance of CRC cells. Besides, miR-665 targeted NOTCH1 to mediate the radiosensitivity of CRC cells. Furthermore, circ_0005615 depletion increased CRC radiosensitivity in vivo. circ_0005615 silencing elevated radiosensitivity of CRC by regulating miR-665/NOTCH1 axis.

Keywords: NOTCH1; circ_0005615; circular RNAs; colorectal cancer; miR-665; radiosensitivity.