LncRNA ANCR promotes proliferation and radiation resistance of nasopharyngeal carcinoma by inhibiting PTEN expression

• Main Authors: Ma X, Zhou J, Liu J, Wu G, Yu Y, Zhu H
• Format: Article
• Language: English
• Published: Dove Medical Press 2018-11-01
• Series: OncoTargets and Therapy
• Subjects: Anti-differentiation noncoding RNA (ANCR); Nasopharyngeal carcinoma (NPC); Phosphatase and tensin homolog (PTEN); Growth; Radiation resistance
• Online Access: https://www.dovepress.com/lncrna-ancr-promotes-proliferation-and-radiation-resistance-of-nasopha-peer-reviewed-article-OTT

Xingkai Ma,1,* Jieyu Zhou,2,* Jianyong Liu,1 Geping Wu,1 Yan Yu,1 Hongyan Zhu,1 Jisheng Liu3 1Department of Otorhinolaryngology, Zhangjiagang First People’s Hospital, Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China; 2Department of Otorhinolaryngology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, P.R. China; 3Department of Otorhinolaryngology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China *These authors contributed equally to this work Introduction: Antidifferentiation noncoding RNA (ANCR) is a newly identified long noncoding RNA, which is reported to function as an oncogene in multiple human cancers. However, its function in nasopharyngeal carcinoma (NPC) and underlying mechanism are still unclear. Materials and methods: We explored the expression of ANCR in NPC tissues and cells by real-time PCR and analyzed the relationship between ANCR expression and clinicopathological characteristics of NPC patients by Pearson’s chi-squared test. Then we inhibited ANCR expression in NPC cells using siRNAs and evaluated the effect of ANCR expression on cell proliferation, colony formation, and radiosensitivity by cell counting kit-8 assay and colony formation assay. We used RT-PCR and Western blot analyses to search target genes of ANCR. Also, we used RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation assay to study the molecular mechanism in this regulation. Results: We found that ANCR was upregulated in NPC tissues and cells. ANCR expression was significantly correlated with tumor size and TNM stage. Further, ANCR knockdown inhibited NPC cell growth and radiation resistance. Mechanistically, we found that PTEN was upregulated in ANCR knockdown NPC cells. In addition, RIP assay indicated that EZH2, the oncogenic histone methyltransferase of polycomb repressive complex 2, interacted with ANCR in NPC cells. More importantly, the binding of EZH2 and deposition of relevant negative histone marker H3K27me3 on PTEN promoter depended on ANCR expression. Conclusion: ANCR expression is upregulated in NPC and promotes NPC growth and radiation resistance through an epigenetic regulation of PTEN expression. Keywords: antidifferentiation noncoding RNA, nasopharyngeal carcinoma, phosphatase and tensin homolog, growth, radiation resistance