Nasopharyngeal carcinoma (NPC) represents a head and neck cancer caused by cancerization of nasal epithelial cells. HOXA10 has been identified to promote proliferation and invasion of NPC cells, but its regulatory mechanism has not been well discussed. Published research work has also pointed out that circular RNAs (circRNAs) could regulate mRNAs to affect NPC tumorigenesis and development.
Aim
To explore the roles of HOXA10 and its specific regulatory mechanism regarding circRNAs in NPC.
Methods
Reverse transcription polymerase chain reaction and western blot were applied to test gene expression. Functional assays were used to evaluate changes in NPC cell phenotypes. Mechanism assays were done to verify RNA-RNA or RNA-protein interaction.
Results
HOXA10 was highly expressed in NPC tissues and cell lines. Moreover, HOXA10 knockdown could restrict NPC cell proliferation, invasion, migration, and epithelial–mesenchymal transition. CircKIAA0368 was upregulated in NPC cells and could elevate HOXA10 expression by sponging miR-6838-5p. Furthermore, circKIAA0368 was unveiled to competitively bind to p300/CREB-binding protein-associated factor (PCAF) to repress acetylation and degradation of HOXA10 protein.
Conclusion
CircKIAA0368 upregulates HOXA10 expression via miR-6838-5p and PCAF, consequently promoting NPCcell and tumor growth.
WahabZTaiEWan HitamWH, et al.Corticosteroid therapy in optic neuropathy secondary to nasopharyngeal carcinoma. Cureus. 2021;13:e13735. DOI: 10.7759/cureus.13735
2.
LeQTColevasADO’SullivanB, et al.Current treatment landscape of nasopharyngeal carcinoma and potential trials evaluating the value of immunotherapy. J Natl Cancer Inst.2019;111:655–663. DOI: 10.1093/jnci/djz044
3.
Ben-AmiTAshSBen-HaroshM, et al.Nasopharyngeal carcinoma in children and young adults—beyond 5-year survival. Pediatr Blood Cancer.2020;67:e28494. DOI: 10.1002/pbc.28494
4.
GuanSWeiJHuangL, et al.Chemotherapy and chemo-resistance in nasopharyngeal carcinoma. Eur J Med Chem.2020;207:112758. DOI: 10.1016/j.ejmech.2020.112758
5.
YiTWLvXXFanH, et al.LncRNA SNHG15 promotes the proliferation of nasopharyngeal carcinoma via sponging miR-141-3p to upregulate KLF9. Eur Rev Med Pharmacol Sci.2020;24:6744–6751. DOI: 10.26355/eurrev_202006_21662
6.
ShenZHZhaoKMDuT. HOXA10 promotes nasopharyngeal carcinoma cell proliferation and invasion via inducing the expression of ZIC2. Eur Rev Med Pharmacol Sci.2017;21:945–952.
7.
KeZXieFZhengC, et al.CircHIPK3 promotes proliferation and invasion in nasopharyngeal carcinoma by abrogating miR-4288-induced ELF3 inhibition. J Cell Physiol.2019;234:1699–1706. DOI: 10.1002/jcp.27041
8.
LiuRZhouMZhangP, et al.Cell proliferation and invasion is promoted by circSERPINA3 in nasopharyngeal carcinoma by regulating miR-944/MDM2 axis. J Cancer.2020;11:3910–3918. DOI: 10.7150/jca.42799
9.
ShuaiMHuangL. High expression of hsa_circRNA_001387 in nasopharyngeal carcinoma and the effect on efficacy of radiotherapy. Onco Targets Ther.2020;13:3965–3973. DOI: 10.2147/ott.s249202
10.
ZhuLLiuYYangY, et al.CircRNA ZNF609 promotes growth and metastasis of nasopharyngeal carcinoma by competing with microRNA-150-5p. Eur Rev Med Pharmacol Sci.2019;23:2817–2826. DOI: 10.26355/eurrev_201904_17558
11.
LiHYouJXueH, et al.CircCTDP1 promotes nasopharyngeal carcinoma progression via a microRNA-320b/HOXA10/TGFβ2 pathway. Int J Mol Med.2020;45:836–846. DOI: 10.3892/ijmm.2020.4467
12.
ChenZHuangJFengY, et al.Screening and bioinformatics analysis of a ceRNA network based on the circular RNAs, miRNAs, and mRNAs in pan-cancer. Cancer Med.2020;9:7279–7292. DOI: 10.1002/cam4.3375
13.
HongXLiuNLiangY, et al.Circular RNA CRIM1 functions as a ceRNA to promote nasopharyngeal carcinoma metastasis and docetaxel chemoresistance through upregulating FOXQ1. Mol Cancer.2020;19:33. DOI: 10.1186/s12943-020-01149-x
14.
TangLXiongWZhangL, et al.circSETD3 regulates MAPRE1 through miR-615-5p and miR-1538 sponges to promote migration and invasion in nasopharyngeal carcinoma. Oncogene. 2021;40:307–321. DOI: 10.1038/s41388-020-01531-5
15.
IngoliaNTHussmannJAWeissmanJS. Ribosome profiling: global views of translation. Cold Spring Harbor Perspect Biol.2019;11. DOI: 10.1101/cshperspect.a032698
16.
KristensenLSAndersenMSStagstedLVW, et al.The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet.2019;20:675–691. DOI: 10.1038/s41576-019-0158-7
17.
ShenSYaoTXuY, et al.CircECE1 activates energy metabolism in osteosarcoma by stabilizing c-Myc. Mol Cancer.2020;19:151. DOI: 10.1186/s12943-020-01269-4
18.
XuJJiLLiangY, et al.CircRNA-SORE mediates sorafenib resistance in hepatocellular carcinoma by stabilizing YBX1. Signal Transduct Target Ther. 2020;5:298. DOI: 10.1038/s41392-020-00375-5
19.
XuLFanSZhaoJ, et al.Increased expression of Cks1 protein is associated with lymph node metastasis and poor prognosis in nasopharyngeal carcinoma. Diagn Pathol.2017;12:2. DOI: 10.1186/s13000-016-0589-9
20.
SerafiniSSantosMMAoun TannuriAC, et al.Is hematoxylin-eosin staining in rectal mucosal and submucosal biopsies still useful for the diagnosis of Hirschsprung disease?Diagn Pathol.2017;12:84. DOI: 10.1186/s13000-017-0673-9
21.
YangJGongYJiangQ, et al.Circular RNA expression profiles in nasopharyngeal carcinoma by sequence analysis. Front Oncol.2020;10:601. DOI: 10.3389/fonc.2020.00601
22.
ShiLShiHLouL, et al.L1-ORF1p and Ago2 are involved in a siRNA-mediated regulation for promoter activity of L1-5’UTR. Folia Histochem Cytobiol.2019;57:56–63. DOI: 10.5603/FHC.a2019.0006
23.
KimYRRyuCSKimJO, et al.Association study of AGO1 and AGO2 genes polymorphisms with recurrent pregnancy loss. Sci Rep.2019;9:15591. DOI: 10.1038/s41598-019-52073-0
24.
BriskinDWangPYBartelDP. The biochemical basis for the cooperative action of microRNAs. Proc Natl Acad Sci U S A.2020;117:17764–17774. DOI: 10.1073/pnas.1920404117
25.
ZhuLHSunLHHuYL, et al.PCAF Impairs endometrial receptivity and embryo implantation by down-regulating β3-integrin expression via HOXA10 acetylation. J Clin Endocrinol Metab.2013;98:4417–4428. DOI: 10.1210/jc.2013-1429
26.
ShepshelovichJGoldstein-MagalLGlobersonA, et al.Protein synthesis inhibitors and the chemical chaperone TMAO reverse endoplasmic reticulum perturbation induced by overexpression of the iodide transporter pendrin. J Cell Sci.2005;118:1577–1586. DOI: 10.1242/jcs.02294
27.
SunXSLiXYChenQY, et al.Future of radiotherapy in nasopharyngeal carcinoma. Br J Radiol.2019;92:20190209. DOI: 10.1259/bjr.20190209
28.
HanBYangXZhangP, et al.DNA Methylation biomarkers for nasopharyngeal carcinoma. PLoS One. 2020;15:e0230524. DOI: 10.1371/journal.pone.0230524
29.
ShuaiMHongJHuangD, et al.Upregulation of circRNA_0000285 serves as a prognostic biomarker for nasopharyngeal carcinoma and is involved in radiosensitivity. Oncol Lett.2018;16:6495–6501. DOI: 10.3892/ol.2018.9471
30.
FanCQuHXiongF, et al.CircARHGAP12 promotes nasopharyngeal carcinoma migration and invasion via ezrin-mediated cytoskeletal remodeling. Cancer Lett.2021;496:41–56. DOI: 10.1016/j.canlet.2020.09.006
31.
AiJTanGWangT, et al.Transcription factor STAT1 promotes the proliferation, migration and invasion of nasopharyngeal carcinoma cells by upregulating LINC01160. Future Oncol. 2021;17:57–69. DOI: 10.2217/fon-2020-0618
32.
GongDZhuHZengL, et al.Overexpression of HOXA10 promotes the growth and metastasis of nasopharyngeal carcinoma. Exp Biol Med. 2021;246:2454–2462. DOI: 10.1177/15353702211030854
33.
FengJChenKDongX, et al.Genome-wide identification of cancer-specific alternative splicing in circRNA. Mol Cancer.2019;18:35. DOI: 10.1186/s12943-019-0996-0
34.
HanTSHurKChoHS, et al.Epigenetic associations between lncRNA/circRNA and miRNA in Hepatocellular Carcinoma. Cancers (Basel).2020;12. DOI: 10.3390/cancers12092622
35.
WeiHLiuDSunJ, et al.Circular RNA circ_0008450 upregulates CXCL9 expression by targeting miR-577 to regulate cell proliferation and invasion in nasopharyngeal carcinoma. Exp Mol Pathol.2019;110:104288. DOI: 10.1016/j.yexmp.2019.104288
36.
LiBZhuLLuC, et al.circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity. Nat Commun.2021;12:295. DOI: 10.1038/s41467-020-20527-z
37.
SongCHanYLuoH, et al.HOXA10 Induces BCL2 expression, inhibits apoptosis, and promotes cell proliferation in gastric cancer. Cancer Med.2019;8:5651–5661. DOI: 10.1002/cam4.2440
38.
StrongMJBaddooMNanboA, et al.Comprehensive high-throughput RNA sequencing analysis reveals contamination of multiple nasopharyngeal carcinoma cell lines with HeLa cell genomes. J Virol.2014;88:10696–10704. DOI: 10.1128/jvi.01457-14
39.
ChanSYChoyKWTsaoSW, et al.Authentication of nasopharyngeal carcinoma tumor lines. Int J Cancer.2008;122:2169–2171. DOI: 10.1002/ijc.23374
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