Upregulation of SOX2-activated lncRNA ANRIL promotes nasopharyngeal carcinoma cell growth

Jian-Hui Wu,Jia Li,Jian-Ming Tang,Xiong-Wen Li

doi:10.1038/s41598-018-21708-z

Abstract

Recent molecularly targeted approaches have gained advances in nasopharyngeal carcinoma treatment. However, the estimated five-year survival rate has not met the desired degree of improvement. Here, we report that upregulation of the expression of the SOX2-activated lncRNA ANRIL is involved in nasopharyngeal carcinoma. ANRIL has been found to be upregulated in clinical nasopharyngeal carcinoma. Using genetic approaches targeting ANRIL in nasopharyngeal carcinoma cells, we found that the knockdown of ANRIL inhibits cell proliferation in vitro and in vivo. Mechanistically, SOX2 binds with ANRIL and increases its RNA level, which upregulates β-catenin signalling, resulting in enhanced nasopharyngeal carcinoma tumourigenesis. Expression levels of ANRIL are positively correlated with SOX2 and β-catenin in clinical nasopharyngeal carcinoma samples. Our findings demonstrate that the SOX2-ANRIL-β-catenin axis plays a critical role in nasopharyngeal carcinoma proliferation and provide a potential therapeutic approach for nasopharyngeal carcinoma patients.

Highlights

Nasopharyngeal carcinoma is one of the most common malignancies of the head and neck, and it has a multifactorial aetiology, presenting a distinct geographical distribution in occurrence, with high incidence rates in North Africa, Southeast Asia, and Southern China[1,2]
To determine the expression of ANRIL in nasopharyngeal carcinoma, qRT-PCR analysis was performed in 122 nasopharyngeal carcinoma tissue samples and 10 normal nasopharyngeal tissue samples
The results showed that ANRIL expression was higher in nasopharyngeal carcinoma tissues compared with normal nasopharyngeal tissues (Fig. 1A)

Summary

Introduction

Nasopharyngeal carcinoma is one of the most common malignancies of the head and neck, and it has a multifactorial aetiology, presenting a distinct geographical distribution in occurrence, with high incidence rates in North Africa, Southeast Asia, and Southern China[1,2]. Recent long non-coding RNAs (lncRNAs) have been recognized as playing critical roles in the progression of nasopharyngeal carcinoma[6,7,8]. The lncRNA ANRIL (CDKN2B antisense RNA1) was initially identified from familial melanoma patients with neural system tumours, and it encodes a 3834-nt RNA consisting of 19 exons that is transcribed in the antisense orientation from the INK4B-ARF-INK4A gene cluster on chromosome 9p21. It contains three important tumour suppressors, p14ARF, p15INK4b, and p16INK4a15,16.

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Conclusion