ZNRD1-AS1 Promotes Nasopharyngeal Carcinoma Cell Invasion and Metastasis by Regulating the MiR-335-ROCK1 Axis

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2020 Jun 18

PMID 32547105

Citations 6

Authors

Qiang Wang

Xinyu Hu

Mingyu Du

Zhiwei Lu

Keshi Yan

Dingliang Zhao

Ning Jiang

Yi Peng

Xia He

Li Yin

Affiliations

Soon will be listed here.

Abstract

Background: Long noncoding RNAs (lncRNAs) are known as key regulators in many cancer types, but their biological functions in nasopharyngeal carcinoma (NPC) remain largely unknown. In the present study, we aim to explore the role of the lncRNA ZNRD1-AS1 in NPC tumor development.

Methods: The role of ZNRD1-AS1 in NPC tissues and cells was explored by using quantitative real-time PCR assay. Cellular behavioral experiments were used in testing NPC cell proliferation, invasion, and migration. Luciferase reporter assay, RNA-binding protein immunoprecipitation, and Western blot analysis were used in estimating the associations among ZNRD1-AS1, miR-335, and ROCK1.

Results: ZNRD1-AS1 expression was elevated in the NPC tissues and cells, and ZNRD1-AS1 overexpression was positively correlated with advanced TNM stage and the presence of lymph node metastasis. Our biological experiments indicated that ZNRD1-AS1 knockdown reduces NPC cell invasion and metastasis. Further analyses revealed that ZNRD1-AS1 as a ceRNA promotes the migration and invasion of NPC cells by sponging miR-335. We provided evidence that ZNRD1-AS1 facilitates the invasion and metastasis of NPC cells via the miR-335-ROCK1 axis.

Conclusion: Our data shed light on the oncogenic role of ZNRD1-AS1 in NPC tumor development, and a promising therapeutic target for NPC was identified.

Citing Articles

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References

Qian X, Jeon C, Yoon H, Agarwal K, Weiss M . Structure of a new nucleic-acid-binding motif in eukaryotic transcriptional elongation factor TFIIS. Nature. 1993; 365(6443):277-9. DOI: 10.1038/365277a0. View

Ho C . Beating 'Guangdong cancer': a review and update on nasopharyngeal cancer. Hong Kong Med J. 2017; 23(5):497-502. DOI: 10.12809/hkmj176834. View

Li D, Song L, Wen Z, Li X, Jie J, Wang Y . Strong evidence for LncRNA ZNRD1-AS1, and its functional Cis- eQTL locus contributing more to the susceptibility of lung cancer. Oncotarget. 2016; 7(24):35813-35817. PMC: 5094964. DOI: 10.18632/oncotarget.8411. View

Guo D, Li Y, Chen Y, Zhang D, Wang X, Lu G . DANCR promotes HCC progression and regulates EMT by sponging miR-27a-3p via ROCK1/LIMK1/COFILIN1 pathway. Cell Prolif. 2019; 52(4):e12628. PMC: 6668976. DOI: 10.1111/cpr.12628. View

Sun X, Su S, Chen C, Han F, Zhao C, Xiao W . Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities. Radiother Oncol. 2013; 110(3):398-403. DOI: 10.1016/j.radonc.2013.10.020. View

Liang H, Zhang C, Guan H, Liu J, Cui Y . LncRNA DANCR promotes cervical cancer progression by upregulating ROCK1 via sponging miR-335-5p. J Cell Physiol. 2018; 234(5):7266-7278. DOI: 10.1002/jcp.27484. View

Prabhu K, Raza A, Karedath T, Raza S, Fathima H, Ahmed E . Non-Coding RNAs as Regulators and Markers for Targeting of Breast Cancer and Cancer Stem Cells. Cancers (Basel). 2020; 12(2). PMC: 7072613. DOI: 10.3390/cancers12020351. View

Razak A, Siu L, Liu F, Ito E, OSullivan B, Chan K . Nasopharyngeal carcinoma: the next challenges. Eur J Cancer. 2010; 46(11):1967-78. DOI: 10.1016/j.ejca.2010.04.004. View

Wang J, Zhang L, Qu R, Zhang L, Huang W . Rho A Regulates Epidermal Growth Factor-Induced Human Osteosarcoma MG63 Cell Migration. Int J Mol Sci. 2018; 19(5). PMC: 5983621. DOI: 10.3390/ijms19051437. View

10.

Wen J, Liu Y, Liu J, Liu L, Song C, Han J . Expression quantitative trait loci in long non-coding RNA ZNRD1-AS1 influence both HBV infection and hepatocellular carcinoma development. Mol Carcinog. 2014; 54(11):1275-82. DOI: 10.1002/mc.22200. View

11.

Zhao Y, Hong L, Wang R, Fan D . Expression and prognostic value of ZNRD1 in esophageal squamous cell carcinoma. Dig Dis Sci. 2008; 54(3):586-92. DOI: 10.1007/s10620-008-0380-1. View

12.

Defert O, Boland S . Rho kinase inhibitors: a patent review (2014 - 2016). Expert Opin Ther Pat. 2017; 27(4):507-515. DOI: 10.1080/13543776.2017.1272579. View

13.

Chen W, Du M, Hu X, Ma H, Zhang E, Wang T . Long noncoding RNA cytoskeleton regulator RNA promotes cell invasion and metastasis by titrating miR-613 to regulate ANXA2 in nasopharyngeal carcinoma. Cancer Med. 2019; 9(3):1209-1219. PMC: 6997049. DOI: 10.1002/cam4.2778. View

14.

Liu X, Sun M, Nie F, Ge Y, Zhang E, Yin D . Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer. 2014; 13:92. PMC: 4021402. DOI: 10.1186/1476-4598-13-92. View

15.

Hong R, Ting L, Ko J, Hsu M, Sheen T, Lou P . Induction chemotherapy with mitomycin, epirubicin, cisplatin, fluorouracil, and leucovorin followed by radiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma. J Clin Oncol. 2001; 19(23):4305-13. DOI: 10.1200/JCO.2001.19.23.4305. View

16.

Fan W, Wang Z, Kyzysztof F, Prange C, Lennon G . A new zinc ribbon gene (ZNRD1) is cloned from the human MHC class I region. Genomics. 2000; 63(1):139-41. DOI: 10.1006/geno.1999.6040. View

17.

Zhang W, Du M, Wang T, Chen W, Wu J, Li Q . Long non-coding RNA LINC01133 mediates nasopharyngeal carcinoma tumorigenesis by binding to YBX1. Am J Cancer Res. 2019; 9(4):779-790. PMC: 6511644. View

18.

Shi D, Wu F, Mu S, Hu B, Zhong B, Gao F . LncRNA AFAP1-AS1 promotes tumorigenesis and epithelial-mesenchymal transition of osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway. J Exp Clin Cancer Res. 2019; 38(1):375. PMC: 6708246. DOI: 10.1186/s13046-019-1363-0. View

19.

Zhou X, Sun R, Luo D, Sun J, Zhang M, Wang M . Upregulated TRIM29 promotes proliferation and metastasis of nasopharyngeal carcinoma via PTEN/AKT/mTOR signal pathway. Oncotarget. 2016; 7(12):13634-50. PMC: 4924667. DOI: 10.18632/oncotarget.7215. View

20.

Yuan J, Yang F, Wang F, Ma J, Guo Y, Tao Q . A long noncoding RNA activated by TGF-β promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 2014; 25(5):666-81. DOI: 10.1016/j.ccr.2014.03.010. View