Knockdown of circNRIP1 sensitizes colorectal cancer to 5‑FU via sponging miR‑532‑3p

Liu,Fanfan; Li,Ruijia; Zhang,Rui; He,Meng; Zhang,Yueli

doi:10.3892/or.2021.8169

Knockdown of circNRIP1 sensitizes colorectal cancer to 5‑FU via sponging miR‑532‑3p

Authors:
- Fanfan Liu
- Ruijia Li
- Rui Zhang
- Meng He
- Yueli Zhang
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Affiliations: Department of Clinical Pharmacy, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450007, P.R. China, Department of Pharmacy, The Eighth Hospital of Xi'an, Xi'an, Shanxi 710061, P.R. China, Department of Critical Care Medicine, Shaanxi Provincial Cancer Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China
Published online on: August 12, 2021 https://doi.org/10.3892/or.2021.8169
Article Number: 218
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the influence of circular RNA nuclear receptor‑interacting protein 1 (circNRIP1) on the chemotherapeutic effect of 5‑fluorouracil (5‑FU) in colorectal cancer (CRC) and reveal its potential molecular mechanisms. The effects of circNRIP1 on cell proliferation, migration and invasion, and apoptosis were evaluated using Cell Counting Kit‑8, Transwell and flow cytometric assays, respectively. A dual‑luciferase reporter assay was performed to verify the potential interaction between circNRIP1 and microRNA (miR)‑532‑3p. The results of the present study indicated that circNRIP1 was upregulated in CRC and its increased expression was associated with CRC progression. Furthermore, overexpression of circNRIP1 promoted CRC cell proliferation, invasion and migration, while it inhibited apoptosis. Knockdown of circNRIP1 significantly enhanced the 5‑FU‑induced inhibition of the viability of HCT116 and SW480 cells. Bioinformatics analysis predicted that miR‑532‑3p was a direct target of circNRIP1, which was further confirmed by a dual‑luciferase reporter assay. miR‑532‑3p silencing reversed the effects of circNRIP1 knockdown on the sensitivity of 5‑FU in the chemotherapy of CRC. The results suggested that circNRIP1 and miR‑532‑3p may be utilized to improve the diagnosis of CRC and serve as diagnostic markers. In conclusion, overexpression of circNRIP1 promoted the progression of CRC, while circNRIP1 silencing sensitized CRC cells to 5‑FU via sponging miR‑532‑3p.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Siegel RL, Miller KD, Fedewa SA, Butterly LF, Anderson JC, Cercek A, Smith RA and Jemal A: Colorectal cancer statistics, 2017. CA Cancer J Clin. 67:177–193. 2017. View Article : Google Scholar : PubMed/NCBI
3	Dekker E, Tanis PJ, Vleugels J, Kasi PM and Wallace MB: Colorectal cancer. Lancet. 394:1467–1480. 2019. View Article : Google Scholar : PubMed/NCBI
4	Meng S, Zhou H, Feng Z, Xu Z, Tang Y, Li P and Wu M: circRNA: Functions and properties of a novel potential biomarker for cancer. Mol Cancer. 16:942017. View Article : Google Scholar : PubMed/NCBI
5	Kristensen LS, Andersen MS, Stagsted L, Ebbesen KK, Hansen TB and Kjems J: The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 20:675–691. 2019. View Article : Google Scholar : PubMed/NCBI
6	Soslau G: Circular RNA (circRNA) was an important bridge in the switch from the RNA world to the DNA world. J Theor Biol. 447:32–40. 2018. View Article : Google Scholar : PubMed/NCBI
7	Ruan H, Xiang Y, Ko J, Li S, Jing Y, Zhu X, Ye Y, Zhang Z, Mills T, Feng J, et al: Comprehensive characterization of circular RNAs in ~1000 human cancer cell lines. Genome Med. 11:552019. View Article : Google Scholar : PubMed/NCBI
8	Lei B, Tian Z, Fan W and Ni B: Circular RNA: A novel biomarker and therapeutic target for human cancers. Int J Med Sci. 16:292–301. 2019. View Article : Google Scholar : PubMed/NCBI
9	Chen LY, Wang L, Ren YX, Pang Z, Liu Y, Sun XD, Tu J, Zhi Z, Qin Y, Sun LN and Li JM: The circular RNA circ-ERBIN promotes growth and metastasis of colorectal cancer by miR-125a-5p and miR-138-5p/4EBP-1 mediated cap-independent HIF-1alpha translation. Mol Cancer. 19:1642020. View Article : Google Scholar : PubMed/NCBI
10	Shang A, Gu C, Wang W, Wang X, Sun J, Zeng B, Chen C, Chang W, Ping Y, Ji P, et al: Exosomal circPACRGL promotes progression of colorectal cancer via the miR-142-3p/miR-506-3p- TGF-β1 axis. Mol Cancer. 19:1172020. View Article : Google Scholar : PubMed/NCBI
11	Li C, He X, Zhang L, Li L and Zhao W: A pair-wise meta-analysis highlights circular RNAs as potential biomarkers for colorectal cancer. BMC Cancer. 19:9572019. View Article : Google Scholar : PubMed/NCBI
12	Liang L and Li L: Down-regulation of circNRIP1 promotes the apoptosis and inhibits the migration and invasion of gastric cancer cells by miR-182/ROCK1 axis. Onco Targets Ther. 13:6279–6288. 2020. View Article : Google Scholar : PubMed/NCBI
13	Fang D and Lu G: Expression and role of nuclear receptor-interacting protein 1 (NRIP1) in stomach adenocarcinoma. Ann Transl Med. 8:12932020. View Article : Google Scholar : PubMed/NCBI
14	Ni XF, Zhao LH, Li G, Hou M, Su M, Zou CL and Deng X: MicroRNA-548-3p and microRNA-576-5p enhance the migration and invasion of esophageal squamous cell carcinoma cells via NRIP1 down-regulation. Neoplasma. 65:881–887. 2018. View Article : Google Scholar : PubMed/NCBI
15	Liang ZZ, Guo C, Zou MM, Meng P and Zhang TT: circRNA-miRNA-mRNA regulatory network in human lung cancer: An update. Cancer Cell Int. 20:1732020. View Article : Google Scholar : PubMed/NCBI
16	Xiong DD, Dang YW, Lin P, Wen DY, He RQ, Luo DZ, Feng ZB and Chen G: A circRNA-miRNA-mRNA network identification for exploring underlying pathogenesis and therapy strategy of hepatocellular carcinoma. J Transl Med. 16:2202018. View Article : Google Scholar : PubMed/NCBI
17	Zhong Y, Du Y, Yang X, Mo Y, Fan C, Xiong F, Ren D, Ye X, Li C, Wang Y, et al: Circular RNAs function as ceRNAs to regulate and control human cancer progression. Mol Cancer. 17:792018. View Article : Google Scholar : PubMed/NCBI
18	Ji Q, Zhang C, Sun X and Li Q: Circular RNAs function as competing endogenous RNAs in multiple types of cancer. Oncol Lett. 15:23–30. 2018.PubMed/NCBI
19	Li Q, Pan X, Zhu D, Deng Z, Jiang R and Wang X: Circular RNA MAT2B promotes glycolysis and malignancy of hepatocellular carcinoma through the miR-338-3p/PKM2 axis under hypoxic stress. Hepatology. 70:1298–1316. 2019. View Article : Google Scholar : PubMed/NCBI
20	Chen X, Chen RX, Wei WS, Li YH, Feng ZH, Tan L, Chen JW, Yuan GJ, Chen SL and Guo SJ: PRMT5 circular RNA promotes metastasis of urothelial carcinoma of the bladder through sponging miR-30c to induce epithelial-mesenchymal transition. Clin Cancer Res. 24:6319–6330. 2018. View Article : Google Scholar : PubMed/NCBI
21	Xu D, Wu Y, Wang X, Hu X, Qin W, Li Y, Wang Y, Zhang Z, Lu S, Sun T, et al: Identification of functional circRNA/miRNA/mRNA regulatory network for exploring prospective therapy strategy of colorectal cancer. J Cell Biochem. 1:297032020.
22	Li X, Ma N, Zhang Y, Wei H, Zhang H, Pang X, Li X, Wu D, Wang D, Yang Z and Zhang S: Circular RNA circNRIP1 promotes migration and invasion in cervical cancer by sponging miR-629-3p and regulating the PTP4A1/ERK1/2 pathway. Cell Death Dis. 11:3992020. View Article : Google Scholar : PubMed/NCBI
23	McQuade RM, Stojanovska V, Bornstein JC and Nurgali K: Colorectal cancer chemotherapy: The evolution of treatment and new approaches. Curr Med Chem. 24:1537–1557. 2017. View Article : Google Scholar : PubMed/NCBI
24	Blondy S, David V, Verdier M, Mathonnet M, Perraud A and Christou N: 5-fluorouracil resistance mechanisms in colorectal cancer: From classical pathways to promising processes. Cancer Sci. 111:3142–3154. 2020. View Article : Google Scholar : PubMed/NCBI
25	Yang W, Gu J, Wang X, Wang Y, Feng M, Zhou D, Guo J and Zhou M: Inhibition of circular RNA CDR1as increases chemosensitivity of 5-FU-resistant BC cells through up-regulating miR-7. J Cell Mol Med. 23:3166–3177. 2019. View Article : Google Scholar : PubMed/NCBI
26	Ren TJ, Liu C, Hou JF and Shan FX: circDDX17 reduces 5-fluorouracil resistance and hinders tumorigenesis in colorectal cancer by regulating miR-31-5p/KANK1 axis. Eur Rev Med Pharmacol Sci. 24:1743–1754. 2020.PubMed/NCBI
27	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
28	Dong Z, Liu Y, Wang Q, Wang H, Ji J, Huang T, Khanal A, Niu H and Cao Y: The circular RNA-NRIP1 plays oncogenic roles by targeting microRNA-505 in the renal carcinoma cell lines. J Cell Biochem. 121:2236–2246. 2020. View Article : Google Scholar : PubMed/NCBI
29	Zhang X, Wang S, Wang H, Cao J, Huang X, Chen Z, Xu P, Sun G, Xu J, Lv J and Xu Z: Circular RNA circNRIP1 acts as a microRNA-149-5p sponge to promote gastric cancer progression via the AKT1/mTOR pathway. Mol Cancer. 18:202019. View Article : Google Scholar : PubMed/NCBI
30	Ouyang X, Yao L, Liu G, Liu S, Gong L and Xiao Y: Loss of androgen receptor promotes HCC invasion and metastasis via activating circ-LNPEP/miR-532-3p/RAB9A signal under hypoxia. Biochem Biophys Res Commun. 557:26–32. 2021. View Article : Google Scholar : PubMed/NCBI
31	Ye J, Liu J, Tang T, Xin L, Bao X and Yan Y: LINC00963 affects the development of colorectal cancer via miR-532-3p/HMGA2 axis. Cancer Cell Int. 21:872021. View Article : Google Scholar : PubMed/NCBI
32	Jin L, Huang S, Guan C and Chang S: ETS1-activated SNHG10 exerts oncogenic functions in glioma via targeting miR-532-3p/FBXL19 axis. Cancer Cell Int. 20:5892020. View Article : Google Scholar : PubMed/NCBI
33	Dai X, Liu J, Guo X, Cheng A, Deng X, Guo L and Wang Z: Circular RNA circFGD4 suppresses gastric cancer progression via modulating miR-532-3p/APC/beta-catenin signalling pathway. Clin Sci (Lond). 134:1821–1839. 2020.PubMed/NCBI
34	Lin J, Qin H, Han Y, Li X, Zhao Y and Zhai G: circNRIP1 Modulates the miR-515-5p/IL-25 axis to control 5-Fu and cisplatin resistance in nasopharyngeal carcinoma. Drug Des Devel Ther. 15:323–330. 2021. View Article : Google Scholar : PubMed/NCBI
35	Xu G, Li M, Wu J, Qin C, Tao Y and He H: Circular RNA circNRIP1 sponges microRNA-138-5p to maintain hypoxia-induced resistance to 5-fluorouracil through HIF-1α-dependent glucose metabolism in gastric carcinoma. Cancer Manag Res. 12:2789–2802. 2020. View Article : Google Scholar : PubMed/NCBI