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European Journal of Medical Research
Published in: European Journal of Medical Research 1/2023

Open Access 01-12-2023 | Kidney Cancer | Research

hsa_circ_0003596, as a novel oncogene, regulates the malignant behavior of renal cell carcinoma by modulating glycolysis

Authors: QingZhi Xie, FuQiang Qin, LiHui Luo, ShaoQuan Deng, Ke Zeng, YunChou Wu, DunMing Liao, Lin Luo, KangNing Wang

Published in: European Journal of Medical Research | Issue 1/2023

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Abstract

Background

This research was planned to analyze hsa_circ_0003596 (circCOL5A1) and glycolysis-focused mechanisms in renal cell carcinoma (RCC).

Methods

circCOL5A1, miR-370-5p, and PRKCSH levels were determined in RCC tissues and selected cell lines by RT-qPCR and/or Western blot. RCC cells after corresponding transfection were tested by colony formation assay, EdU assay, Transwell assay, and flow cytometry to analyze cell proliferation, invasion, migration, and apoptosis. Meanwhile, glycolysis in cells was evaluated by measuring glucose consumption, lactic acid, and ATP production, as well as immunoblotting for HK2 and PKM2. In addition, circCOL5A1 knockdown was performed in animal experiments to observe tumor growth and glycolysis. Finally, the ceRNA network between circCOL5A1, miR-370-5p, and PRKCSH was studied by luciferase reporter assay and RIP experiment.

Results

circCOL5A1 and PRKCSH were highly expressed and miR-370-5p was poorly expressed in RCC. circCOL5A1 knockdown depressed RCC proliferation, invasion, migration, and glycolysis, and enhanced apoptosis. circCOL5A1 competitively adsorbed miR-370-5p. Artificial upregulation of miR-370-5p saved the pro-tumor effect of circCOL5A1 on RCC cells, as evidenced by suppression of tumor malignancy and glycolysis. miR-370-5p targeted PRKCSH. PRKCSH overexpression contributed to a reversal of the anti-tumor effect of circCOL5A1 silencing. Silencing circCOL5A1 inhibited RCC tumor growth and glycolysis.

Conclusions

circCOL5A1 regulates the malignant behavior of RCC by modulating glycolysis.
Appendix
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Literature
1.
Qian Y, Li Y, Xu L, Chen K, Liu N, Yang X, Lv Q, Li R, Zhou C, Xu Z, et al. Tumor cell-derived exosomal circ-PRKCI promotes proliferation of renal cell carcinoma via regulating miR-545–3p/CCND1 axis. Cancers (Basel). 2022;15(1):123.CrossRefPubMed
2.
Couto-Cunha A, Jeronimo C, Henrique R. Circulating tumor cells as biomarkers for renal cell carcinoma: ready for prime time? Cancers (Basel). 2022;15(1):287.CrossRefPubMed
3.
Akhtar M, Al-Bozom IA, Al Hussain T. Molecular and metabolic basis of clear cell carcinoma of the kidney. Adv Anat Pathol. 2018;25(3):189–96.CrossRefPubMed
4.
5.
Zhao B, Huang C, Pan J, Hu H, Liu X, Zhang K, Zhou F, Shi X, Wu J, Yu B, et al. circPLIN2 promotes clear cell renal cell carcinoma progression by binding IGF2BP proteins and miR-199a-3p. Cell Death Dis. 2022;13(12):1030.CrossRefPubMedPubMedCentral
6.
Frey L, Klumper N, Schmidt D, Kristiansen G, Toma M, Ritter M, Alajati A, Ellinger J. CircEHD2, CircNETO2 and CircEGLN3 as diagnostic and prognostic biomarkers for patients with renal cell carcinoma. Cancers (Basel). 2021;13(9):2177.CrossRefPubMed
7.
Liang Y, Cen J, Huang Y, Fang Y, Wang Y, Shu G, Pan Y, Huang K, Dong J, Zhou M, et al. CircNTNG1 inhibits renal cell carcinoma progression via HOXA5-mediated epigenetic silencing of Slug. Mol Cancer. 2022;21(1):224.CrossRefPubMedPubMedCentral
8.
Zhang H, Ma M. Circ_0101692 knockdown retards the development of clear cell renal cell carcinoma through miR-384/FN1 pathway. Transl Oncol. 2023;28: 101612.CrossRefPubMedPubMedCentral
9.
Grammatikaki S, Katifelis H, Farooqi AA, Stravodimos K, Karamouzis MV, Souliotis K, Varvaras D, Gazouli M. An overview of epigenetics in clear cell renal cell carcinoma. In Vivo. 2023;37(1):1–10.CrossRefPubMedPubMedCentral
10.
Morais M, Dias F, Teixeira AL, Medeiros R. MicroRNAs and altered metabolism of clear cell renal cell carcinoma: potential role as aerobic glycolysis biomarkers. Biochim Biophys Acta Gen Subj. 2017;1861(9):2175–85.CrossRefPubMed
11.
Yao D, Nong L, Qin M, Wu S, Yao S. Identifying circRNA-miRNA interaction based on multi-biological interaction fusion. Front Microbiol. 2022;13: 987930.CrossRefPubMedPubMedCentral
12.
Ji D, Hou L, Xie C, Feng H, Bao D, Teng Y, Liu J, Cui T, Wang X, Xu Y, et al. Deoxyelephantopin suppresses pancreatic cancer progression in vitro and in vivo by targeting linc00511/miR-370-5p/p21 promoter axis. J Oncol. 2022;2022:3855462.CrossRefPubMedPubMedCentral
13.
MiR-370-5p inhibits the progression of breast cancer via targeting LUC7L3. J Recept Signal Transduct Res 2022, 42(2):214.
14.
Feng F, Yang J, Chen A, Cui M, Li L. Long non-coding RNA long intergenic non-protein coding RNA 1232 promotes cell proliferation, migration and invasion in bladder cancer via modulating miR-370-5p/PIM3 axis. J Tissue Eng Regen Med. 2022;16(6):575–85.CrossRefPubMed
15.
Zhang Y, Liu F, Feng Y, Xu X, Wang Y, Zhu S, Dong J, Zhao S, Xu B, Feng N. CircRNA circ_0006156 inhibits the metastasis of prostate cancer by blocking the ubiquitination of S100A9. Cancer Gene Ther. 2022;29(11):1731–41.CrossRefPubMedPubMedCentral
16.
17.
18.
Singh M, Afonso J, Sharma D, Gupta R, Kumar V, Rani R, Baltazar F, Kumar V. Targeting monocarboxylate transporters (MCTs) in cancer: how close are we to the clinics? Semin Cancer Biol. 2023;90:1–14.CrossRefPubMed
19.
Schreier A, Zappasodi R, Serganova I, Brown KA, Demaria S, Andreopoulou E. Facts and perspectives: implications of tumor glycolysis on immunotherapy response in triple negative breast cancer. Front Oncol. 2022;12:1061789.CrossRefPubMed
20.
Wu Z, Wu J, Zhao Q, Fu S, Jin J. Emerging roles of aerobic glycolysis in breast cancer. Clin Transl Oncol. 2020;22(5):631–46.CrossRefPubMed
21.
Zhang MX, Wang JL, Mo CQ, Mao XP, Feng ZH, Li JY, Lin HS, Song HD, Xu QH, Wang YH, et al. CircME1 promotes aerobic glycolysis and sunitinib resistance of clear cell renal cell carcinoma through cis-regulation of ME1. Oncogene. 2022;41(33):3979–90.CrossRefPubMedPubMedCentral
22.
Shen S, Jiang M, Deng W, Liu X, Xiong J, Zeng Z, Zhao H, Zeng X, Fu B. Circ_0008717 promotes renal cell carcinoma progression by upregulating FBXO17 via targeting miR-217. J Gene Med. 2022;24(11): e3418.CrossRefPubMed
23.
Lucarelli G, Loizzo D, Franzin R, Battaglia S, Ferro M, Cantiello F, Castellano G, Bettocchi C, Ditonno P, Battaglia M. Metabolomic insights into pathophysiological mechanisms and biomarker discovery in clear cell renal cell carcinoma. Expert Rev Mol Diagn. 2019;19(5):397–407.CrossRefPubMed
24.
Massari F, Ciccarese C, Santoni M, Brunelli M, Piva F, Modena A, Bimbatti D, Fantinel E, Santini D, Cheng L, et al. Metabolic alterations in renal cell carcinoma. Cancer Treat Rev. 2015;41(9):767–76.CrossRefPubMed
25.
Balliet RM, Capparelli C, Guido C, Pestell TG, Martinez-Outschoorn UE, Lin Z, Whitaker-Menezes D, Chiavarina B, Pestell RG, Howell A, et al. Mitochondrial oxidative stress in cancer-associated fibroblasts drives lactate production, promoting breast cancer tumor growth: understanding the aging and cancer connection. Cell Cycle. 2011;10(23):4065–73.CrossRefPubMedPubMedCentral
26.
Byun JK. Tumor lactic acid: a potential target for cancer therapy. Arch Pharm Res. 2023;46(2):90–110.CrossRefPubMed
27.
28.
Wang JX, Choi SYC, Niu X, Kang N, Xue H, Killam J, Wang Y. Lactic acid and an acidic tumor microenvironment suppress anticancer immunity. Int J Mol Sci. 2020;21(21):8363.CrossRefPubMedPubMedCentral
29.
Guo D, Tong Y, Jiang X, Meng Y, Jiang H, Du L, Wu Q, Li S, Luo S, Li M, et al. Aerobic glycolysis promotes tumor immune evasion by hexokinase2-mediated phosphorylation of IkappaBalpha. Cell Metab. 2022;34(9):1312-1324 e1316.CrossRefPubMed
30.
Ganapathy-Kanniappan S. Linking tumor glycolysis and immune evasion in cancer: emerging concepts and therapeutic opportunities. Biochim Biophys Acta Rev Cancer. 2017;1868(1):212–20.CrossRefPubMed
31.
Zhang Y, Li L, Lu KX, Yu LB, Meng J, Liu CY. LncRNA SNHG3 is responsible for the deterioration of colorectal carcinoma through regulating the miR-370-5p/EZH1 axis. Eur Rev Med Pharmacol Sci. 2021;25(19):6131–7.PubMed
32.
Sudo M, Mori S, Madan V, Yang H, Leong G, Koeffler HP. Short-hairpin RNA library: identification of therapeutic partners for gefitinib-resistant non-small cell lung cancer. Oncotarget. 2015;6(2):814–24.CrossRefPubMed
33.
Lei R, Zhou M, Zhang S, Luo J, Qu C, Wang Y, Guo P, Huang R. Potential role of PRKCSH in lung cancer: bioinformatics analysis and a case study of Nano ZnO. Nanoscale. 2022;14(12):4495–510.CrossRefPubMed
Metadata
Title
hsa_circ_0003596, as a novel oncogene, regulates the malignant behavior of renal cell carcinoma by modulating glycolysis
Authors
QingZhi Xie
FuQiang Qin
LiHui Luo
ShaoQuan Deng
Ke Zeng
YunChou Wu
DunMing Liao
Lin Luo
KangNing Wang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-023-01288-z

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