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Published in: Journal of Translational Medicine 1/2021

Open Access 01-12-2021 | Prostate Cancer | Research

CircSERPINA3 regulates SERPINA3-mediated apoptosis, autophagy and aerobic glycolysis of prostate cancer cells by competitively binding to MiR-653-5p and recruiting BUD13

Authors: Zengshu Xing, Sailian Li, Zhenxiang Liu, Chong Zhang, Zhiming Bai

Published in: Journal of Translational Medicine | Issue 1/2021

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Abstract

Background

Prostate cancer (PCa) belongs to an epithelial malignancy that occurs in the prostate gland and is the most common malignancy of the male genitourinary system. Referring to related literature, circSERPINA3 has been reported to be up-regulated in PCa. However, its biological function remains unclear.

Purpose

This study aimed to reveal the specific role and relevant molecular mechanism of circSERPINA3 in PCa.

Methods

RT-qPCR was used to examine gene expression and functional analyses were conducted to verify the effect of circSERPINA3 on cell apoptosis, autophagy and aerobic glycolysis in PCa cells. Mechanism assays were applied to evaluate the relationship among circSERPINA3/miR-653-5p/SERPINA3/BUD13.

Results

CircSERPINA3 was verified to be up-regulated in PCa cells and to inhibit cell apoptosis while promoting aerobic glycolysis and autophagy in PCa cells. CircSERPINA3 and SERPINA3 were also testified to bind to miR-653-5p through a line of mechanism experiments. Moreover, it was discovered that circSERPINA3 could stabilize SERPINA3 mRNA via recruiting BUD13. Additionally, SERPINA3 was verified to inhibit cell apoptosis, while promoting aerobic glycolysis and autophagy in PCa cells.

Conclusions

Our study suggested that circSERPINA3 regulated apoptosis, autophagy and aerobic glycolysis of PCa cells by competitively binding to miR-653-5p and recruiting BUD13.

Graphic abstract

Appendix
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Literature
1.
go back to reference Sebesta EM, Anderson CB. The surgical management of prostate cancer. Semin Oncol. 2017;44(5):347–57.CrossRef Sebesta EM, Anderson CB. The surgical management of prostate cancer. Semin Oncol. 2017;44(5):347–57.CrossRef
2.
go back to reference Ren SC, Chen R, Sun YH. Prostate cancer research in China. Asian J Androl. 2013;15(3):350–3.CrossRef Ren SC, Chen R, Sun YH. Prostate cancer research in China. Asian J Androl. 2013;15(3):350–3.CrossRef
3.
go back to reference Smits M, Mehra N, Sedelaar M, Gerritsen W, Schalken JA. Molecular biomarkers to guide precision medicine in localized prostate cancer. Expert Rev Mol Diagn. 2017;17(8):791–804.CrossRef Smits M, Mehra N, Sedelaar M, Gerritsen W, Schalken JA. Molecular biomarkers to guide precision medicine in localized prostate cancer. Expert Rev Mol Diagn. 2017;17(8):791–804.CrossRef
4.
go back to reference Dori M, Bicciato S. Integration of Bioinformatic Predictions and Experimental Data to Identify circRNA-miRNA Associations. Genes. 2019;10(9):642.CrossRef Dori M, Bicciato S. Integration of Bioinformatic Predictions and Experimental Data to Identify circRNA-miRNA Associations. Genes. 2019;10(9):642.CrossRef
5.
go back to reference Xiang Z, Xu C, Wu G, Liu B, Wu D. CircRNA-UCK2 increased TET1 inhibits proliferation and invasion of prostate cancer cells via sponge MiRNA-767-5p. Open Med (Warsaw, Poland). 2019;14:833–42.CrossRef Xiang Z, Xu C, Wu G, Liu B, Wu D. CircRNA-UCK2 increased TET1 inhibits proliferation and invasion of prostate cancer cells via sponge MiRNA-767-5p. Open Med (Warsaw, Poland). 2019;14:833–42.CrossRef
6.
go back to reference Yang Z, Qu CB, Zhang Y, Zhang WF, Wang DD, Gao CC, et al. Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression through the circAMOTL1L-miR-193a-5p-Pcdha pathway. Oncogene. 2019;38(14):2516–32.CrossRef Yang Z, Qu CB, Zhang Y, Zhang WF, Wang DD, Gao CC, et al. Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression through the circAMOTL1L-miR-193a-5p-Pcdha pathway. Oncogene. 2019;38(14):2516–32.CrossRef
7.
go back to reference Cai C, Zhi Y, Wang K, Zhang P, Ji Z, Xie C, et al. CircHIPK3 overexpression accelerates the proliferation and invasion of prostate cancer cells through regulating miRNA-338-3p. Onco Targets Ther. 2019;12:3363–72.CrossRef Cai C, Zhi Y, Wang K, Zhang P, Ji Z, Xie C, et al. CircHIPK3 overexpression accelerates the proliferation and invasion of prostate cancer cells through regulating miRNA-338-3p. Onco Targets Ther. 2019;12:3363–72.CrossRef
8.
go back to reference Ge S, Sun C, Hu Q, Guo Y, Xia G, Mi Y, et al. Differential expression profiles of circRNAs in human prostate cancer based on chip and bioinformatic analysis. Int J Clin Exp Pathol. 2020;13(5):1045–52.PubMedPubMedCentral Ge S, Sun C, Hu Q, Guo Y, Xia G, Mi Y, et al. Differential expression profiles of circRNAs in human prostate cancer based on chip and bioinformatic analysis. Int J Clin Exp Pathol. 2020;13(5):1045–52.PubMedPubMedCentral
9.
go back to reference Liberti MV, Locasale JW. The Warburg Effect: How Does it Benefit Cancer Cells? Trends Biochem Sci. 2016;41(3):211–8.CrossRef Liberti MV, Locasale JW. The Warburg Effect: How Does it Benefit Cancer Cells? Trends Biochem Sci. 2016;41(3):211–8.CrossRef
10.
go back to reference Lu J, Tan M, Cai Q. The Warburg effect in tumor progression: mitochondrial oxidative metabolism as an anti-metastasis mechanism. Cancer Lett. 2015;356(2 Pt A):156–64.CrossRef Lu J, Tan M, Cai Q. The Warburg effect in tumor progression: mitochondrial oxidative metabolism as an anti-metastasis mechanism. Cancer Lett. 2015;356(2 Pt A):156–64.CrossRef
11.
go back to reference Xu W, Zeng F, Li S, Li G, Lai X, Wang QJ, et al. Crosstalk of protein kinase C ε with Smad2/3 promotes tumor cell proliferation in prostate cancer cells by enhancing aerobic glycolysis. Cell Mol Life Sci CMLS. 2018;75(24):4583–98.CrossRef Xu W, Zeng F, Li S, Li G, Lai X, Wang QJ, et al. Crosstalk of protein kinase C ε with Smad2/3 promotes tumor cell proliferation in prostate cancer cells by enhancing aerobic glycolysis. Cell Mol Life Sci CMLS. 2018;75(24):4583–98.CrossRef
12.
go back to reference Wang L, Xiong H, Wu F, Zhang Y, Wang J, Zhao L, et al. Hexokinase 2-mediated Warburg effect is required for PTEN- and p53-deficiency-driven prostate cancer growth. Cell Rep. 2014;8(5):1461–74.CrossRef Wang L, Xiong H, Wu F, Zhang Y, Wang J, Zhao L, et al. Hexokinase 2-mediated Warburg effect is required for PTEN- and p53-deficiency-driven prostate cancer growth. Cell Rep. 2014;8(5):1461–74.CrossRef
13.
go back to reference Zhang Y, Shi Z, Li Z, Wang X, Zheng P, Li H. Circ_0057553/miR-515-5p regulates prostate cancer cell proliferation, apoptosis, migration, invasion and aerobic glycolysis by targeting YES1. Onco Targets Ther. 2020;13:11289–99.CrossRef Zhang Y, Shi Z, Li Z, Wang X, Zheng P, Li H. Circ_0057553/miR-515-5p regulates prostate cancer cell proliferation, apoptosis, migration, invasion and aerobic glycolysis by targeting YES1. Onco Targets Ther. 2020;13:11289–99.CrossRef
14.
go back to reference Altesha MA, Ni T, Khan A, Liu K, Zheng X. Circular RNA in cardiovascular disease. J Cell Physiol. 2019;234(5):5588–600.CrossRef Altesha MA, Ni T, Khan A, Liu K, Zheng X. Circular RNA in cardiovascular disease. J Cell Physiol. 2019;234(5):5588–600.CrossRef
15.
go back to reference Li Y, Lu J, Bai F, Xiao Y, Guo Y, Dong Z. Ginsenoside Rg3 suppresses proliferation and induces apoptosis in human osteosarcoma. Biomed Res Int. 2018;2018:4306579.PubMedPubMedCentral Li Y, Lu J, Bai F, Xiao Y, Guo Y, Dong Z. Ginsenoside Rg3 suppresses proliferation and induces apoptosis in human osteosarcoma. Biomed Res Int. 2018;2018:4306579.PubMedPubMedCentral
16.
go back to reference YiRen H, YingCong Y, Sunwu Y, Keqin L, Xiaochun T, Senrui C, et al. Long noncoding RNA MALAT1 regulates autophagy associated chemoresistance via miR-23b-3p sequestration in gastric cancer. Mol Cancer. 2017;16(1):174.CrossRef YiRen H, YingCong Y, Sunwu Y, Keqin L, Xiaochun T, Senrui C, et al. Long noncoding RNA MALAT1 regulates autophagy associated chemoresistance via miR-23b-3p sequestration in gastric cancer. Mol Cancer. 2017;16(1):174.CrossRef
17.
go back to reference Sotthibundhu A, McDonagh K, von Kriegsheim A, Garcia-Munoz A, Klawiter A, Thompson K, et al. Rapamycin regulates autophagy and cell adhesion in induced pluripotent stem cells. Stem Cell Res Ther. 2016;7(1):166.CrossRef Sotthibundhu A, McDonagh K, von Kriegsheim A, Garcia-Munoz A, Klawiter A, Thompson K, et al. Rapamycin regulates autophagy and cell adhesion in induced pluripotent stem cells. Stem Cell Res Ther. 2016;7(1):166.CrossRef
18.
go back to reference Wang W, Wang S, Zhang Z, Li J, Xie W, Su Y, et al. Identification of potential traumatic spinal cord injury related circular RNA-microRNA networks by sequence analysis. Zhongguo xiu fu chong jian wai ke za zhi Zhongguo xiufu chongjian waike zazhi Chin J Reparative Reconstr Surg. 2020;34(2):213–9. Wang W, Wang S, Zhang Z, Li J, Xie W, Su Y, et al. Identification of potential traumatic spinal cord injury related circular RNA-microRNA networks by sequence analysis. Zhongguo xiu fu chong jian wai ke za zhi Zhongguo xiufu chongjian waike zazhi Chin J Reparative Reconstr Surg. 2020;34(2):213–9.
19.
go back to reference Zhou J, Zhang S, Chen Z, He Z, Xu Y, Li Z. CircRNA-ENO1 promoted glycolysis and tumor progression in lung adenocarcinoma through upregulating its host gene ENO1. Cell Death Dis. 2019;10(12):885.CrossRef Zhou J, Zhang S, Chen Z, He Z, Xu Y, Li Z. CircRNA-ENO1 promoted glycolysis and tumor progression in lung adenocarcinoma through upregulating its host gene ENO1. Cell Death Dis. 2019;10(12):885.CrossRef
20.
go back to reference Wang Z, Lei X, Wu FX. Identifying cancer-specific circRNA-RBP binding sites based on deep learning. Molecules (Basel, Switzerland). 2019;24(22):4035.CrossRef Wang Z, Lei X, Wu FX. Identifying cancer-specific circRNA-RBP binding sites based on deep learning. Molecules (Basel, Switzerland). 2019;24(22):4035.CrossRef
21.
go back to reference Song Y, Gao F, Peng Y, Yang X. Long non-coding RNA DBH-AS1 promotes cancer progression in diffuse large B-cell lymphoma by targeting FN1 via RNA-binding protein BUD13. Cell Biol Int. 2020;44(6):1331–40.CrossRef Song Y, Gao F, Peng Y, Yang X. Long non-coding RNA DBH-AS1 promotes cancer progression in diffuse large B-cell lymphoma by targeting FN1 via RNA-binding protein BUD13. Cell Biol Int. 2020;44(6):1331–40.CrossRef
22.
go back to reference Fernández-Barral A, Orgaz JL, Gomez V, del Peso L, Calzada MJ, Jiménez B. Hypoxia negatively regulates antimetastatic PEDF in melanoma cells by a hypoxia inducible factor-independent, autophagy dependent mechanism. PLoS ONE. 2012;7(3):e32989.CrossRef Fernández-Barral A, Orgaz JL, Gomez V, del Peso L, Calzada MJ, Jiménez B. Hypoxia negatively regulates antimetastatic PEDF in melanoma cells by a hypoxia inducible factor-independent, autophagy dependent mechanism. PLoS ONE. 2012;7(3):e32989.CrossRef
23.
go back to reference Cao LL, Pei XF, Qiao X, Yu J, Ye H, Xi CL, et al. SERPINA3 silencing inhibits the migration, invasion, and liver metastasis of colon cancer cells. Dig Dis Sci. 2018;63(9):2309–19.CrossRef Cao LL, Pei XF, Qiao X, Yu J, Ye H, Xi CL, et al. SERPINA3 silencing inhibits the migration, invasion, and liver metastasis of colon cancer cells. Dig Dis Sci. 2018;63(9):2309–19.CrossRef
24.
go back to reference Carnagarin R, Carlessi R, Newsholme P, Dharmarajan AM, Dass CR. Pigment epithelium-derived factor stimulates skeletal muscle glycolytic activity through NADPH oxidase-dependent reactive oxygen species production. Int J Biochem Cell Biol. 2016;78:229–36.CrossRef Carnagarin R, Carlessi R, Newsholme P, Dharmarajan AM, Dass CR. Pigment epithelium-derived factor stimulates skeletal muscle glycolytic activity through NADPH oxidase-dependent reactive oxygen species production. Int J Biochem Cell Biol. 2016;78:229–36.CrossRef
25.
go back to reference Prostate cancer. Nursing standard (Royal College of Nursing (Great Britain): 1987). 2016;30(40):17. Prostate cancer. Nursing standard (Royal College of Nursing (Great Britain): 1987). 2016;30(40):17.
26.
go back to reference Teo MY, Rathkopf DE, Kantoff P. Treatment of advanced prostate cancer. Annual review of medicine. 2019;70:479–99.CrossRef Teo MY, Rathkopf DE, Kantoff P. Treatment of advanced prostate cancer. Annual review of medicine. 2019;70:479–99.CrossRef
27.
go back to reference Jiang H, Lv DJ, Song XL, Wang C, Yu YZ, Zhao SC. Upregulated circZMIZ1 promotes the proliferation of prostate cancer cells and is a valuable marker in plasma. Neoplasma. 2020;67(1):68–77.CrossRef Jiang H, Lv DJ, Song XL, Wang C, Yu YZ, Zhao SC. Upregulated circZMIZ1 promotes the proliferation of prostate cancer cells and is a valuable marker in plasma. Neoplasma. 2020;67(1):68–77.CrossRef
28.
go back to reference He H, Li J, Luo M, Wei Q. Inhibitory role of circRNA_100395 in the proliferation and metastasis of prostate cancer cells. J Int Med Res. 2021;49(2):300060521992215.CrossRef He H, Li J, Luo M, Wei Q. Inhibitory role of circRNA_100395 in the proliferation and metastasis of prostate cancer cells. J Int Med Res. 2021;49(2):300060521992215.CrossRef
29.
go back to reference Liu R, Zhou M, Zhang P, Zhao Y, Zhang Y. Cell proliferation and invasion is promoted by circSERPINA3 in nasopharyngeal carcinoma by regulating miR-944/MDM2 axis. J Cancer. 2020;11(13):3910–8.CrossRef Liu R, Zhou M, Zhang P, Zhao Y, Zhang Y. Cell proliferation and invasion is promoted by circSERPINA3 in nasopharyngeal carcinoma by regulating miR-944/MDM2 axis. J Cancer. 2020;11(13):3910–8.CrossRef
30.
go back to reference Li F, Li H, Hou Y. Identification and analysis of survival-associated ceRNA triplets in prostate adenocarcinoma. Oncol Lett. 2019;18(4):4040–7.PubMedPubMedCentral Li F, Li H, Hou Y. Identification and analysis of survival-associated ceRNA triplets in prostate adenocarcinoma. Oncol Lett. 2019;18(4):4040–7.PubMedPubMedCentral
31.
go back to reference Huang C, Deng H, Wang Y, Jiang H, Xu R, Zhu X, et al. Circular RNA circABCC4 as the ceRNA of miR-1182 facilitates prostate cancer progression by promoting FOXP4 expression. J Cell Mol Med. 2019;23(9):6112–9.CrossRef Huang C, Deng H, Wang Y, Jiang H, Xu R, Zhu X, et al. Circular RNA circABCC4 as the ceRNA of miR-1182 facilitates prostate cancer progression by promoting FOXP4 expression. J Cell Mol Med. 2019;23(9):6112–9.CrossRef
32.
go back to reference Zheng Y, Chen CJ, Lin ZY, Li JX, Liu J, Lin FJ, et al. Circ_KATNAL1 regulates prostate cancer cell growth and invasiveness through the miR-145–3p/WISP1 pathway. Biochem Cell Biol Biochimie et biologie cellulaire. 2020;98(3):396–404.CrossRef Zheng Y, Chen CJ, Lin ZY, Li JX, Liu J, Lin FJ, et al. Circ_KATNAL1 regulates prostate cancer cell growth and invasiveness through the miR-145–3p/WISP1 pathway. Biochem Cell Biol Biochimie et biologie cellulaire. 2020;98(3):396–404.CrossRef
33.
go back to reference Mohibi S, Chen X, Zhang J. Cancer the’RBP’eutics-RNA-binding proteins as therapeutic targets for cancer. Pharmacol Ther. 2019;203:10739.CrossRef Mohibi S, Chen X, Zhang J. Cancer the’RBP’eutics-RNA-binding proteins as therapeutic targets for cancer. Pharmacol Ther. 2019;203:10739.CrossRef
34.
go back to reference Cao H, Gao R, Yu C, Chen L, Feng Y. The RNA-binding protein FXR1 modulates prostate cancer progression by regulating FBXO4. Funct Integr Genomics. 2019;19(3):487–96.CrossRef Cao H, Gao R, Yu C, Chen L, Feng Y. The RNA-binding protein FXR1 modulates prostate cancer progression by regulating FBXO4. Funct Integr Genomics. 2019;19(3):487–96.CrossRef
35.
go back to reference Feng Y, Yang Y, Zhao X, Fan Y, Zhou L, Rong J, et al. Circular RNA circ0005276 promotes the proliferation and migration of prostate cancer cells by interacting with FUS to transcriptionally activate XIAP. Cell Death Dis. 2019;10(11):792.CrossRef Feng Y, Yang Y, Zhao X, Fan Y, Zhou L, Rong J, et al. Circular RNA circ0005276 promotes the proliferation and migration of prostate cancer cells by interacting with FUS to transcriptionally activate XIAP. Cell Death Dis. 2019;10(11):792.CrossRef
36.
go back to reference Han L, Huang C, Zhang S. The RNA-binding protein SORBS2 suppresses hepatocellular carcinoma tumourigenesis and metastasis by stabilizing RORA mRNA. Liver Int. 2019;39(11):2190–203.CrossRef Han L, Huang C, Zhang S. The RNA-binding protein SORBS2 suppresses hepatocellular carcinoma tumourigenesis and metastasis by stabilizing RORA mRNA. Liver Int. 2019;39(11):2190–203.CrossRef
37.
go back to reference Pan Z, Cai J, Lin J, Zhou H, Peng J, Liang J, et al. A novel protein encoded by circFNDC3B inhibits tumor progression and EMT through regulating Snail in colon cancer. Mol Cancer. 2020;19(1):71.CrossRef Pan Z, Cai J, Lin J, Zhou H, Peng J, Liang J, et al. A novel protein encoded by circFNDC3B inhibits tumor progression and EMT through regulating Snail in colon cancer. Mol Cancer. 2020;19(1):71.CrossRef
38.
go back to reference Zhang M, Huang N, Yang X, Luo J, Yan S, Xiao F, et al. A novel protein encoded by the circular form of the SHPRH gene suppresses glioma tumorigenesis. Oncogene. 2018;37(13):1805–14.CrossRef Zhang M, Huang N, Yang X, Luo J, Yan S, Xiao F, et al. A novel protein encoded by the circular form of the SHPRH gene suppresses glioma tumorigenesis. Oncogene. 2018;37(13):1805–14.CrossRef
Metadata
Title
CircSERPINA3 regulates SERPINA3-mediated apoptosis, autophagy and aerobic glycolysis of prostate cancer cells by competitively binding to MiR-653-5p and recruiting BUD13
Authors
Zengshu Xing
Sailian Li
Zhenxiang Liu
Chong Zhang
Zhiming Bai
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-021-03063-2

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