Abstract
Circular RNAs function as important regulators in the pathogenesis of human cancers, including nasopharyngeal carcinoma (NPC). We aimed to explore the functions of circ_0028007 in NPC development. Quantitative real-time polymerase chain reaction assay was employed for the levels of circ_0028007, NUAK family kinase 1, microRNA-656-3p (miR-656-3p), and E74 like ETS transcription factor 2 (ELF2). RNase R assay was used to verify the feature of circ_0028007. Cell Counting Kit-8 assay and colony formation assay were performed to assess cell growth. Wound-healing assay and transwell assay were adopted to analyze cell migration and invasion. Tube formation assay was conducted for cell angiogenic capacity. Flow cytometry analysis was performed for cell apoptosis. Western blot assay was conducted for protein levels. Compared to normal tissues and cells, circ_0028007 level was elevated in NPC tissues and cells. Knockdown of circ_0028007 repressed NPC cell growth, migration, invasion, and angiogenesis, facilitated apoptosis in vitro and blocked tumor growth in vivo. Moreover, circ_0028007 silencing could regulate the AMP-activated protein kinase/mammalian target of rapamycin pathway in NPC cells. Circ_0028007 promoted the malignant behaviors of NPC cells via acting as miR-656-3p sponge. In addition, ELF2 was demonstrated to be the target gene of miR-656-3p. MiR-656-3p overexpression restrained NPC cell malignant phenotypes, while ELF2 elevation reversed the effects. Circ_0028007 contributed to the progression of NPC by decoying miR-656-3p and elevating ELF2. The findings might provide potential targets for NPC therapy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
An Y, Cai H, Zhang Y, Liu S, Duan Y, Sun D, Chen X, He X (2018) circZMYM2 competed endogenously with miR-335-5p to regulate JMJD2C in pancreatic cancer. Cell Physiol Biochem 51:2224–2236. https://doi.org/10.1159/000495868
Chen T, Qin S, Gu Y, Pan H, Bian D (2019a) Long non-coding RNA NORAD promotes the occurrence and development of non-small cell lung cancer by adsorbing MiR-656-3p. Mol Genet Genomic Med 7:e757. https://doi.org/10.1002/mgg3.757
Chen YP, Chan ATC, Le QT, Blanchard P, Sun Y, Ma J (2019b) Nasopharyngeal carcinoma. Lancet 394:64–80. https://doi.org/10.1016/S0140-6736(19)30956-0
Chen S, Lv L, Zhan Z, Wang X, You Z, Luo X, You H (2020) Silencing of long noncoding RNA SRRM2-AS exerts suppressive effects on angiogenesis in nasopharyngeal carcinoma via activating MYLK-mediated cGMP-PKG signaling pathway. J Cell Physiol 235:7757–7768. https://doi.org/10.1002/jcp.29382
Faubert B, Vincent EE, Poffenberger MC, Jones RG (2015) The AMP-activated protein kinase (AMPK) and cancer: many faces of a metabolic regulator. Cancer Lett 356:165–170. https://doi.org/10.1016/j.canlet.2014.01.018
Jeck WR, Sharpless NE (2014) Detecting and characterizing circular RNAs. Nat Biotechnol 32:453–461. https://doi.org/10.1038/nbt.2890
Jiang C, Cheng Z, Jiang T, Xu Y, Wang B (2020) MicroRNA-34a inhibits cell invasion and epithelial-mesenchymal transition via targeting AXL/PI3K/AKT/Snail signaling in nasopharyngeal carcinoma. Genes Genomics 42:971–978. https://doi.org/10.1007/s13258-020-00963-3
Ke KJ, Wang CY, Li P, Huang XW, Zhang SL, Li X, Cui XF (2020) Hsa_circ_001193 regulates proliferation and apoptosis of nasopharyngeal carcinoma cells through targeting mir-496. Eur Rev Med Pharmacol Sci 24:3069–3076. https://doi.org/10.26355/eurrev_202003_20671
Lee AWM, Ng WT, Chan JYW, Corry J, Makitie A, Mendenhall WM, Rinaldo A, Rodrigo JP, Saba NF, Strojan P, Suarez C, Vermorken JB, Yom SS, Ferlito A (2019) Management of locally recurrent nasopharyngeal carcinoma. Cancer Treat Rev 79:101890. https://doi.org/10.1016/j.ctrv.2019.101890
Li M, Li Y, Yu M (2020) CircRNA ZNF609 knockdown suppresses cell growth via modulating miR-188/ELF2 axis in nasopharyngeal carcinoma. Onco Targets Ther 13:2399–2409. https://doi.org/10.2147/OTT.S234230
Liu Y, Tao Z, Qu J, Zhou X, Zhang C (2017) Long non-coding RNA PCAT7 regulates ELF2 signaling through inhibition of miR-134-5p in nasopharyngeal carcinoma. Biochem Biophys Res Commun 491:374–381. https://doi.org/10.1016/j.bbrc.2017.07.093
Liu R, Zhou M, Zhang P, Zhao Y, Zhang Y (2020a) Cell proliferation and invasion is promoted by circSERPINA3 in nasopharyngeal carcinoma by regulating miR-944/MDM2 axis. J Cancer 11:3910–3918. https://doi.org/10.7150/jca.42799
Liu Y, Qi X, Zhao Z, Song D, Wang L, Zhai Q, Zhang X, Zhao P, Xiang X (2020b) TIPE1-mediated autophagy suppression promotes nasopharyngeal carcinoma cell proliferation via the AMPK/mTOR signalling pathway. J Cell Mol Med 24:9135–9144. https://doi.org/10.1111/jcmm.15550
Lu J, Liu QH, Wang F, Tan JJ, Deng YQ, Peng XH, Liu X, Zhang B, Xu X, Li XP (2018) Exosomal miR-9 inhibits angiogenesis by targeting MDK and regulating PDK/AKT pathway in nasopharyngeal carcinoma. J Exp Clin Cancer Res 37:147. https://doi.org/10.1186/s13046-018-0814-3
Luo X, He X, Liu X, Zhong L, Hu W (2020) miR-96-5p suppresses the progression of nasopharyngeal carcinoma by targeting CDK1. Onco Targets Ther 13:7467–7477. https://doi.org/10.2147/OTT.S248338
Mai S, Xiao R, Shi L, Zhou X, Yang T, Zhang M, Weng N, Zhao X, Wang R, Liu J, Sun R, Qin H, Wang H (2019) MicroRNA-18a promotes cancer progression through SMG1 suppression and mTOR pathway activation in nasopharyngeal carcinoma. Cell Death Dis 10:819. https://doi.org/10.1038/s41419-019-2060-9
Murugan AK (2019) mTOR: role in cancer, metastasis and drug resistance. Semin Cancer Biol 59:92–111. https://doi.org/10.1016/j.semcancer.2019.07.003
Panda AC (2018) Circular RNAs Act as miRNA sponges. Adv Exp Med Biol 1087:67–79. https://doi.org/10.1007/978-981-13-1426-1_6
Peng Y, Croce CM (2016) The role of microRNAs in human cancer. Signal Transduct Target Ther 1:15004. https://doi.org/10.1038/sigtrans.2015.4
Perri F, Della Vittoria Scarpati G, Caponigro F, Ionna F, Longo F, Buonopane S, Muto P, Di Marzo M, Pisconti S, Solla R (2019) Management of recurrent nasopharyngeal carcinoma: current perspectives. Onco Targets Ther 12:1583–1591. https://doi.org/10.2147/OTT.S188148
Petersson F (2015) Nasopharyngeal carcinoma: a review. Semin Diagn Pathol 32:54–73. https://doi.org/10.1053/j.semdp.2015.02.021
Qiongna D, Jiafeng Z, Yalin H, Ping H, Chuan Z, Xiaojie J, Miaomiao Z, Yiting S, Hui Z (2020) Implication of hsa_circ_0028007 in reinforcing migration, invasion, and chemo-tolerance of nasopharyngeal carcinoma cells. J Clin Lab Anal 34:e23409. https://doi.org/10.1002/jcla.23409
Ramjiawan RR, Griffioen AW, Duda DG (2017) Anti-angiogenesis for cancer revisited: is there a role for combinations with immunotherapy? Angiogenesis 20:185–204. https://doi.org/10.1007/s10456-017-9552-y
Rong D, Sun H, Li Z, Liu S, Dong C, Fu K, Tang W, Cao H (2017) An emerging function of circRNA-miRNAs-mRNA axis in human diseases. Oncotarget 8:73271–73281. https://doi.org/10.18632/oncotarget.19154
Sun H, Xi P, Sun Z, Wang Q, Zhu B, Zhou J, Jin H, Zheng W, Tang W, Cao H, Cao X (2018) Circ-SFMBT2 promotes the proliferation of gastric cancer cells through sponging miR-182-5p to enhance CREB1 expression. Cancer Manage Res 10:5725–5734. https://doi.org/10.2147/CMAR.S172592
Tian X, Liu Y, Wang Z, Wu S (2020) lncRNA SNHG8 promotes aggressive behaviors of nasopharyngeal carcinoma via regulating miR-656-3p/SATB1 axis. Biomed Pharmacother 131:110564. https://doi.org/10.1016/j.biopha.2020.110564
Wei KR, Yu YL, Yang YY, Ji MF, Yu BH, Liang ZH, Reng X (2010) Epidemiological trends of nasopharyngeal carcinoma in China. Asian Pac J Cancer Prev 11:29–32
Wei H, Liu D, Sun J, Mao Y, Zhao L, Zhu W, Xu G, Gao Z (2019) Circular RNA circ_0008450 upregulates CXCL9 expression by targeting miR-577 to regulate cell proliferation and invasion in nasopharyngeal carcinoma. Exp Mol Pathol 110:104288. https://doi.org/10.1016/j.yexmp.2019.104288
Yin Y, Long J, He Q, Li Y, Liao Y, He P, Zhu W (2019) Emerging roles of circRNA in formation and progression of cancer. J Cancer 10:5015–5021. https://doi.org/10.7150/jca.30828
Zhu L, Liu Y, Yang Y, Mao XM, Yin ZD (2019) CircRNA ZNF609 promotes growth and metastasis of nasopharyngeal carcinoma by competing with microRNA-150-5p. Eur Rev Med Pharmacol Sci 23:2817–2826. https://doi.org/10.26355/eurrev_201904_17558
Zong G, Han J, Yue Z, Liu Y, Cui Z, Shi L (2020) Downregulation of miR-204 facilitates the progression of nasopharyngeal carcinoma by targeting CXCR4 through NF-kappaB signaling pathway. J BUON 25:1098–1104
Acknowledgements
None.
Funding
None.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
10528_2022_10205_MOESM1_ESM.tif
Supplementary file1 (TIF 519 KB)—The selection of miR-656-3p and ELF2. (A and B) The expression of miR-1179, miR-326, miR-331-3p, miR-346, miR-496 and miR-656-3p in SUNE-1 and 5-8F cells transfected with si-NC or si-circ_0028007 was detected by qRT-PCR. (C and D) The mRNA levels of MDK, MARCH5, ELF2, LPAR1, MUAK1 and KLF9 in SUNE-1 and 5-8F cells transfected with miR-NC or miR-656-3p were detected by qRT-PCR. *P<0.05.
Rights and permissions
About this article
Cite this article
Ma, X., Li, Y. Circ_0028007 Aggravates the Malignancy of Nasopharyngeal Carcinoma by Regulating miR-656-3p/ELF2 Axis. Biochem Genet 60, 2069–2086 (2022). https://doi.org/10.1007/s10528-022-10205-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10528-022-10205-8