<p>Circ_0007031 Serves as a Sponge of miR-760 to Regulate the Growth and Chemoradiotherapy Resistance of Colorectal Cancer via Regulating DCP1A</p>

Abstract

Background: 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 mRNAdecapping 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.

CircPRDM2 Contributes to Doxorubicin Resistance of Osteosarcoma by Elevating EZH2 via Sponging miR-760

“… 17 Moreover, miR-760 could regulate the chemoresistance of cancers through lncRNA KCNQ1OT1/miR-760/PPP1R1B axis, 35 miR-760/ITGB1 axis 16 and circ_0007031/miR-760/DCP1A axis. 15 However, it remains unclear about the effects and regulatory mechanisms of miR-760 in DXR resistance in OS. Our data indicated that miR-760 downregulation abated the suppressive roles of circPRDM2 knockdown in DXR resistance and cell malignant characteristics in DXR-resistant OS cells, indicating circPRDM2 enhanced DXR resistance by sponging miR-760.…”

“…For instance, Wang et al confirmed that miR-760 repressed colorectal cancer (CRC) progression and 5-FU resistance by targeting DCP1A. 15 Yang et al unraveled that miR-760 was able to decrease gemcitabine resistance in pancreatic cancer by binding to ITGB1. 16 In OS, Yin et al demonstrated that miR-760 served as a tumor inhibitor via interacting with HDGF.…”

Oncogenic Functions and Clinical Significance of Circular RNAs in Colorectal Cancer

“…In this study, authors claim that high expression of circPRKDC increases β-catenin and c-Myc levels, leading to activation of Wnt/βcatenin pathway in 5-FU resistant CRC cells via miR-375 deletion or FOXM1 (Forkhead box protein M1) overexpression [ 214 ]. Hsa_circ_0007031 is proven as upregulated in 5-FU chemoradiation-resistant CRC cells [ 215 , 216 ], and in 5-FU resistant cell lines [ 217 ]. Xiong et al, 2017 [ 215 ] first bioinformatically predicted signaling pathways involving hsa_circ_0007031, and then Wang et al, 2020 [ 216 ] and He et al, 2020 [ 217 ] presented functional roles of the cicrRNA and proved its notability as a target for overcoming 5-FU and radiation resistance in CRC.…”

“…Hsa_circ_0007031 is proven as upregulated in 5-FU chemoradiation-resistant CRC cells [ 215 , 216 ], and in 5-FU resistant cell lines [ 217 ]. Xiong et al, 2017 [ 215 ] first bioinformatically predicted signaling pathways involving hsa_circ_0007031, and then Wang et al, 2020 [ 216 ] and He et al, 2020 [ 217 ] presented functional roles of the cicrRNA and proved its notability as a target for overcoming 5-FU and radiation resistance in CRC. He et al, 2020 [ 217 ] described the sponging of miR-133b followed by increasing expression of ABCC5 (ATP-binding cassette subfamily C member 5) as a mechanism involving hsa_circ_0007031 in 5-FU resistance, while Wang et al, 2020, [ 216 ] reported the miR-760/DCP1A axis as an underlying mechanism of hsa_circ_0007031 action.…”

“…Xiong et al, 2017 [ 215 ] first bioinformatically predicted signaling pathways involving hsa_circ_0007031, and then Wang et al, 2020 [ 216 ] and He et al, 2020 [ 217 ] presented functional roles of the cicrRNA and proved its notability as a target for overcoming 5-FU and radiation resistance in CRC. He et al, 2020 [ 217 ] described the sponging of miR-133b followed by increasing expression of ABCC5 (ATP-binding cassette subfamily C member 5) as a mechanism involving hsa_circ_0007031 in 5-FU resistance, while Wang et al, 2020, [ 216 ] reported the miR-760/DCP1A axis as an underlying mechanism of hsa_circ_0007031 action. Abu et al, 2019 [ 218 ] found via microarray that hsa_circ_32883 is upregulated in chemoresistant to 5-FU and oxaliplatin cell line model and is probably involved in drug resistance by sponging miR-130b-5p.…”