Cancer Management and Research (Sep 2020)
Circ_0007031 Serves as a Sponge of miR-760 to Regulate the Growth and Chemoradiotherapy Resistance of Colorectal Cancer via Regulating DCP1A
Abstract
Yuanyuan Wang,1,2,* Hua Wang,3,* Jian Zhang,2 Zhifen Chu,2 Pu Liu,2 Xing Zhang,2 Chao Li,2 Xiaosong Gu1 1Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, People’s Republic of China; 2Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Pharmacy, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chao LiDepartment of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang 050031, Hebei, People’s Republic of ChinaEmail [email protected] GuAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, People’s Republic of ChinaTel +86-0311-85917000Email [email protected]: Colorectal cancer (CRC) is a kind of malignant tumor, and the development of chemoradiotherapy resistance (CRR) increases the difficulty of its treatment. The role of circular RNAs (circRNAs) in cancer progression has been well documented. Nevertheless, the function of circ_0007031 in the growth and CRR of CRC has not been well elucidated.Methods: CRR cell lines were constructed using 5-Fu and radiation. Cell counting kit 8 (CCK8) assay was employed to measure the 5-Fu resistance and proliferation of cells. Clonogenic assay was used to evaluate the radiation resistance of cells. Also, the expression of circ_0007031 and microRNA-760 (miR-760) was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The cell cycle distribution and apoptosis of cells were assessed by flow cytometry. Besides, the levels of apoptosis-related protein and mRNA-decapping enzyme 1a (DCP1A) protein were measured by Western blot (WB) analysis. Further, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to confirm the interaction between miR-760 and circ_0007031 or DCP1A. In addition, animal experiments were performed to evaluate the function of silenced circ_0007031 on the 5-Fu and radiation resistance of CRC tumors.Results: Circ_0007031 expression was markedly increased in CRC tissues and cells, especially in CRC resistant cells. Circ_0007031 knockdown hindered proliferation, induced cell cycle arrest in the G0/G1 phase, enhanced apoptosis, and lowered the CRR of CRC resistant cells. Further, miR-760 could be targeted by circ_0007031, and its inhibitor could reverse the inhibition effect of circ_0007031 knockdown on the growth and CRR of CRC resistant cells. Moreover, DCP1A was a target of miR-760, and its overexpression could invert the suppression effect of miR-760 overexpression on the growth and CRR of CRC resistant cells. Circ_0007031 silencing could enhance the sensitivity of CRC tumors to 5-Fu and radiation to markedly reduce CRC tumor growth in vivo.Conclusion: Circ_0007031 might play a positive role in the CRR of CRC through regulating the miR-760/DCP1A axis, which might provide a new approach for treating the CRR of CRC.Keywords: colorectal cancer, CRR, circ_0007031, miR-760, DCP1A
