CircNFATC3 Facilitated the Progression of Oral Squamous Cell Carcinoma Via the MiR-520h/LDHA Axis

Overview

Journal Open Med (Wars)

Specialty General Medicine

Date 2023 Jul 3

PMID 37398901

Authors

Hongguo Xie

Xiaopeng Lu

Affiliations

Soon will be listed here.

Abstract

The aim of this study was to verify the effects of circular RNA nuclear factor of activated T-cells, cytoplasmic 3 (circNFATC3), in oral squamous cell carcinoma (OSCC) development. The levels of circNFATC3, microRNA-520h (miR-520h), and lactate dehydrogenase A (LDHA) were measured by qRT-PCR and western blot analysis. The cellular functions were assessed by using commercial kits, MTT assay, EdU assay, flow cytometry analysis, and transwell assay. The interactions between miR-520h and circNFATC3 or LDHA were confirmed by dual-luciferase reporter assay. Finally, the mice test was enforced to evaluate the character of circNFATC3. We observed that the contents of circNFATC3 and LDHA were upregulated and miR-520h levels were downregulated in OSCC tissues compared with those in paracancerous tissues. For functional analysis, circNFATC3 knockdown repressed the cell glycolysis metabolism, cell proliferation, migration, and invasion, although it improved cell apoptosis in OSCC cells. LDHA could regulate the development of OSCC. circNFATC3 acted as a miR-520h sponge to modulate LDHA expression. In addition, the absence of circNFATC3 subdued tumor growth . In conclusion, circNFATC3 promoted the advancement of OSCC by adjusting the miR-520h/LDHA axis.

Citing Articles

Nuclear Factor of Activated T Cells (NFAT) Proteins as Targeted Molecules in Diseases: A Narrative Review.

Mozafari M, Md Hashim S, Ahmad Amin Noordin K, Zainal S, Azlina A Cureus. 2025; 16(12):e75844.

PMID: 39822413 PMC: 11736229. DOI: 10.7759/cureus.75844.

References

Scapoli L, Palmieri A, Lo Muzio L, Pezzetti F, Rubini C, Girardi A . MicroRNA expression profiling of oral carcinoma identifies new markers of tumor progression. Int J Immunopathol Pharmacol. 2011; 23(4):1229-34. DOI: 10.1177/039463201002300427. View

Warnakulasuriya S . Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2008; 45(4-5):309-16. DOI: 10.1016/j.oraloncology.2008.06.002. View

Su W, Shen Y, Wang Y, Wang F, Hong X, Chen Y . circPHIP promotes oral squamous cell carcinoma progression by sponging miR-142-5p and regulating PHIP and ACTN4 expression. Mol Ther Nucleic Acids. 2020; 23:185-199. PMC: 7744814. DOI: 10.1016/j.omtn.2020.10.038. View

Yu L, Gong X, Sun L, Zhou Q, Lu B, Zhu L . The Circular RNA Cdr1as Act as an Oncogene in Hepatocellular Carcinoma through Targeting miR-7 Expression. PLoS One. 2016; 11(7):e0158347. PMC: 4938625. DOI: 10.1371/journal.pone.0158347. View

Ban E, Kim D, Kim J, Kang S, Lee J, Jeong J . Lactate Dehydrogenase A as a Potential New Biomarker for Thyroid Cancer. Endocrinol Metab (Seoul). 2021; 36(1):96-105. PMC: 7937852. DOI: 10.3803/EnM.2020.819. View

Shang T, Zhou X, Chen W . LINC01123 Promotes the Progression of Colorectal Cancer via miR-625-5p/LASP1 Axis. Cancer Biother Radiopharm. 2020; 36(9):765-773. DOI: 10.1089/cbr.2020.3740. View

Bolos V, Peinado H, Perez-Moreno M, Fraga M, Esteller M, Cano A . The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J Cell Sci. 2003; 116(Pt 3):499-511. DOI: 10.1242/jcs.00224. View

Liu J, Jiang X, Zou A, Mai Z, Huang Z, Sun L . circIGHG-Induced Epithelial-to-Mesenchymal Transition Promotes Oral Squamous Cell Carcinoma Progression via miR-142-5p/IGF2BP3 Signaling. Cancer Res. 2020; 81(2):344-355. DOI: 10.1158/0008-5472.CAN-20-0554. View

Su C, Wang M, Hong C, Chen H, Su Y, Wu C . miR-520h is crucial for DAPK2 regulation and breast cancer progression. Oncogene. 2017; 36(41):5770. DOI: 10.1038/onc.2017.231. View

10.

Garzon R, Marcucci G, Croce C . Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov. 2010; 9(10):775-89. PMC: 3904431. DOI: 10.1038/nrd3179. View

11.

Li F, Li C, Li X, Li Y, Zhong Y, Ling L . Altered circular RNA expression profiles in the non-ischemic thalamus in focal cortical infarction mice. Aging (Albany NY). 2020; 12(13):13206-13219. PMC: 7377861. DOI: 10.18632/aging.103424. View

12.

Li T, Guo H, Zhao X, Jin J, Zhang L, Li H . Gastric Cancer Cell Proliferation and Survival Is Enabled by a Cyclophilin B/STAT3/miR-520d-5p Signaling Feedback Loop. Cancer Res. 2016; 77(5):1227-1240. DOI: 10.1158/0008-5472.CAN-16-0357. View

13.

Sheppard S, Santosa E, Lau C, Violante S, Giovanelli P, Kim H . Lactate dehydrogenase A-dependent aerobic glycolysis promotes natural killer cell anti-viral and anti-tumor function. Cell Rep. 2021; 35(9):109210. PMC: 8221253. DOI: 10.1016/j.celrep.2021.109210. View

14.

Wang J, Jiang C, Li N, Wang F, Xu Y, Shen Z . The circEPSTI1/mir-942-5p/LTBP2 axis regulates the progression of OSCC in the background of OSF via EMT and the PI3K/Akt/mTOR pathway. Cell Death Dis. 2020; 11(8):682. PMC: 7443145. DOI: 10.1038/s41419-020-02851-w. View

15.

He T, Li X, Xie D, Tian L . Overexpressed circPVT1 in oral squamous cell carcinoma promotes proliferation by serving as a miRNA sponge. Mol Med Rep. 2019; 20(4):3509-3518. PMC: 6755181. DOI: 10.3892/mmr.2019.10615. View

16.

Feng L, E L, Soloveiv M, Wang D, Zhang B, Dong Y . Synergistic cytotoxicity of cisplatin and Taxol in overcoming Taxol resistance through the inhibition of LDHA in oral squamous cell carcinoma. Oncol Lett. 2015; 9(4):1827-1832. PMC: 4356296. DOI: 10.3892/ol.2015.2931. View

17.

Zheng F, Wang M, Li Y, Huang C, Tao D, Xie F . CircNR3C1 inhibits proliferation of bladder cancer cells by sponging miR-27a-3p and downregulating cyclin D1 expression. Cancer Lett. 2019; 460:139-151. DOI: 10.1016/j.canlet.2019.06.018. View

18.

van Zyl A, Bunn B . Clinical features of oral cancer. SADJ. 2013; 67(10):566-9. View

19.

Yan X, Zhang M, Li B, Ji X, Wu H, Zhang Q . RAI14 Regulated by circNFATC3/miR-23b-3p axis Facilitates Cell Growth and Invasion in Gastric Cancer. Cell Transplant. 2021; 30:9636897211007055. PMC: 8044574. DOI: 10.1177/09636897211007055. View

20.

Bloebaum M, Poort L, Bockmann R, Kessler P . Survival after curative surgical treatment for primary oral squamous cell carcinoma. J Craniomaxillofac Surg. 2014; 42(8):1572-6. DOI: 10.1016/j.jcms.2014.01.046. View