KIF9‑AS1 promotes nasopharyngeal carcinoma progression by suppressing miR‑16

You,Huizeng; Wang,Shuyong; Yu,Sa

doi:10.3892/ol.2020.12104

KIF9‑AS1 promotes nasopharyngeal carcinoma progression by suppressing miR‑16

Authors:
- Huizeng You
- Shuyong Wang
- Sa Yu
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Affiliations: Department of Otolaryngology, Weifang Traditional Chinese Hospital, Weifang, Shandong 261041, P.R. China, Department of Otorhinolaryngology‑Head and Neck Surgery, Zhuji People's Hospital of Zhejiang Province, Zhuji, Zhejiang 311800, P.R. China
Published online on: September 15, 2020 https://doi.org/10.3892/ol.2020.12104
Article Number: 241
Copyright: © You et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding RNAs (lncRNAs) have been reported to serve a crucial role in the progression of nasopharyngeal carcinoma (NPC); however, the underlying molecular mechanisms of lncRNA KIF9‑AS1 in the tumorigenesis of NPC remains poorly understood. Reverse transcription‑quantitative PCR was used to analyze the expression levels of KIF9‑AS1 and microRNA (miR)‑16, and Cell Counting Kit‑8, wound healing and Transwell assays were used to determine the cell viability, invasion and migration, respectively, of NPC cells. In addition, a dual‑luciferase reporter assay was used to analyze the direct interaction between KIF9‑AS1 and miR‑16. NPC stage was classified according to the seventh edition of the AJCC staging system. The results revealed that KIF9‑AS1 expression levels were upregulated in NPC tissues and cell lines. In addition, miR‑16 was demonstrated to directly interact with KIF9‑AS1 and inhibit KIF9‑AS1 expression levels, whereas the miR‑16 inhibitor rescued the effects of the KIF9‑AS1‑knockdown in NPC cells. Furthermore, the expression levels of KIF9‑AS1 were upregulated, while those of miR‑16 were downregulated in NPC tissues. Notably, the expression levels of KIF9‑AS1 were observed to be significantly more upregulated in advanced tumors (III‑IV vs. I‑II) and patients with high KIF9‑AS1 expression levels exhibited a worse prognosis. In conclusion, the findings of the present study suggested that KIF9‑AS1 may promote the progression of NPC by targeting miR‑16, thus KIF9‑AS1 may be a novel molecular target for NPC therapy.

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1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Tang LL, Chen WQ, Xue WQ, He YQ, Zheng RS, Zeng YX and Jia WH: Global trends in incidence and mortality of nasopharyngeal carcinoma. Cancer Lett. 374:22–30. 2016. View Article : Google Scholar : PubMed/NCBI
3	Chua MLK, Wee JTS, Hui EP and Chan ATC: Nasopharyngeal carcinoma. Lancet. 387:1012–1024. 2016. View Article : Google Scholar : PubMed/NCBI
4	Petersson F and Nasopharyngeal carcinoma: A review. Semin Diagn Pathol. 32:54–73. 2015. View Article : Google Scholar : PubMed/NCBI
5	El-Mofty SK: Human papillomavirus-related head and neck squamous cell carcinoma variants. Semin Diagn Pathol. 32:23–31. 2015. View Article : Google Scholar : PubMed/NCBI
6	Lo KW, To KF and Huang DP: Focus on nasopharyngeal carcinoma. Cancer Cell. 5:423–428. 2004. View Article : Google Scholar : PubMed/NCBI
7	Lee AW, Ma BB, Ng WT and Chan AT: Management of nasopharyngeal carcinoma: Current practice and future perspective. J Clin Oncol. 33:3356–3364. 2015. View Article : Google Scholar : PubMed/NCBI
8	Di W, Li Q, Shen W, Guo H and Zhao S: The long non-coding RNA HOTAIR promotes thyroid cancer cell growth, invasion and migration through the miR-1-CCND2 axis. Am J Cancer Res. 7:1298–1309. 2017.PubMed/NCBI
9	Zheng P, Li H, Xu P, Wang X, Shi Z, Han Q and Li Z: High lncRNA HULC expression is associated with poor prognosis and promotes tumor progression by regulating epithelial-mesenchymal transition in prostate cancer. Arch Med Sci. 14:679–686. 2018. View Article : Google Scholar : PubMed/NCBI
10	Zhang C, Su C, Song Q, Dong F, Yu S and Huo J: lncRNA PICART1 suppressed non-small cell lung cancer cells proliferation and invasion by targeting AKT1 signaling pathway. Am J Transl Res. 10:4193–4201. 2018.PubMed/NCBI
11	Wang W, Shen H, Cao G and Huang J: Long non-coding RNA XIST predicts poor prognosis and promotes malignant phenotypes in osteosarcoma. Oncol Lett. 17:256–262. 2019.PubMed/NCBI
12	Wang S, Hou Y, Chen W, Wang J, Xie W, Zhang X and Zeng L: KIF9AS1, LINC01272 and DIO3OS lncRNAs as novel biomarkers for inflammatory bowel disease. Mol Med Rep. 17:2195–2202. 2018.PubMed/NCBI
13	He L and Hannon GJ: MicroRNAs: Small RNAs with a big role in gene regulation. Nat Rev Genet. 5:522–531. 2004. View Article : Google Scholar : PubMed/NCBI
14	Yeh YM, Chuang CM, Chao KC and Wang LH: MicroRNA-138 suppresses ovarian cancer cell invasion and metastasis by targeting SOX4 and HIF-1α. Int J Cancer. 133:867–878. 2013. View Article : Google Scholar : PubMed/NCBI
15	Jia XD, Niu P, Xie CC and Liu HJ: Long noncoding RNA PXN-AS1-L promotes the malignancy of nasopharyngeal carcinoma cells via upregulation of SAPCD2. Cancer Med. 8:4278–4291. 2019.PubMed/NCBI
16	Ventura A and Jacks T: MicroRNAs and cancer: Short RNAs go a long way. Cell. 136:586–591. 2009. View Article : Google Scholar : PubMed/NCBI
17	Edge SB and Compton CC: The American joint committee on cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI
18	Backliwal G, Hildinger M, Hasija V and Wurm FM: High-density transfection with HEK-293 cells allows doubling of transient titers and removes need for a priori DNA complex formation with PEI. Biotechnol Bioeng. 99:721–727. 2008. View Article : Google Scholar : PubMed/NCBI
19	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
20	Drummond GB, Paterson DJ and McGrath JC: ARRIVE: New guidelines for reporting animal research. J Physiol. 588:25172010. View Article : Google Scholar : PubMed/NCBI
21	Cao SM, Simons MJ and Qian CN: The prevalence and prevention of nasopharyngeal carcinoma in China. Chin J Cancer. 30:114–119. 2011. View Article : Google Scholar : PubMed/NCBI
22	Wang M, Ji YQ, Song ZB, Ma XX, Zou YY and Li XS: Knockdown of lncRNA ZFAS1 inhibits progression of nasopharyngeal carcinoma by sponging miR-135a. Neoplasma. 66:939–945. 2019. View Article : Google Scholar : PubMed/NCBI
23	Zhang W, Guo Q, Liu G, Zheng F, Chen J, Huang D, Ding L, Yang X, Song E, Xiang Y and Yao H: NKILA represses nasopharyngeal carcinoma carcinogenesis and metastasis by NF-kB pathway inhibition. PLoS Genet. 15:e10083252019. View Article : Google Scholar : PubMed/NCBI
24	Kong YG, Cui M, Chen SM, Xu Y, Xu Y and Tao ZZ: lncRNA-LINC00460 facilitates nasopharyngeal carcinoma tumorigenesis through sponging miR-149-5p to up-regulate IL6. Gene. 639:77–84. 2018. View Article : Google Scholar : PubMed/NCBI
25	Wang X, Jin Q, Wang X, Chen W and Cai Z: lncRNA ZFAS1 promotes proliferation and migration and inhibits apoptosis in nasopharyngeal carcinoma via the PI3K/AKT pathway in vitro. Cancer Biomark. 26:171–182. 2019. View Article : Google Scholar : PubMed/NCBI
26	Wang LX, Wan C, Dong ZB, Wang BH, Liu HY and Li Y: Integrative analysis of long noncoding RNA (lncRNA), microRNA (miRNA) and mRNA expression and construction of a competing endogenous RNA (ceRNA) network in metastatic melanoma. Med Sci Monit. 25:2896–2907. 2019. View Article : Google Scholar : PubMed/NCBI
27	Tay Y, Rinn J and Pandolfi PP: The multilayered complexity of ceRNA crosstalk and competition. Nature. 505:344–352. 2014. View Article : Google Scholar : PubMed/NCBI
28	Shi S, Li D, Li Y, Feng Z, Du Y and Nie Y: lncRNA CR749391 acts as a tumor suppressor to upregulate KLF6 expression via interacting with miR-181a in gastric cancer. Exp Ther Med. 19:569–578. 2020.PubMed/NCBI
29	Li L, Ma TT, Ma YH and Jiang YF: lncRNA HCG18 contributes to nasopharyngeal carcinoma development by modulating miR-140/CCND1 and Hedgehog signaling pathway. Eur Rev Med Pharmacol Sci. 23:10387–10399. 2019.PubMed/NCBI
30	Lian Y, Xiong F, Yang L, Bo H, Gong Z, Wang Y, Wei F, Tang Y, Li X, Liao Q, et al: Long noncoding RNA AFAP1-AS1 acts as a competing endogenous RNA of miR-423-5p to facilitate nasopharyngeal carcinoma metastasis through regulating the Rho/Rac pathway. J Exp Clin Cancer Res. 37:2532018. View Article : Google Scholar : PubMed/NCBI
31	Zhang S, Wang W, Wu X, Liu W and Ding F: miR-16-5p modulates the radiosensitivity of cervical cancer cells via regulating coactivator-associated arginine methyltransferase 1. Pathol Int. 70:12–20. 2020. View Article : Google Scholar : PubMed/NCBI
32	Yu Q, Liu P, Han G, Xue X and Ma D: CircRNA circPDSS1 promotes bladder cancer by downregulating miR-16. Biosci Rep. 40:BSR201919612020. View Article : Google Scholar : PubMed/NCBI
33	Chava S, Reynolds CP, Pathania AS, Gorantla S, Poluektova LY, Coulter DW, Gupta SC, Pandey MK and Challagundla KB: miR-15a-5p, miR-15b-5p, and miR-16-5p inhibit tumor progression by directly targeting MYCN in neuroblastoma. Mol Oncol. 14:180–196. 2020. View Article : Google Scholar : PubMed/NCBI