The long noncoding RNA SPRY4-IT1 increases the proliferation of human breast cancer cells by upregulating ZNF703 expression.

Yongguo Shi,Keming Wang,Yun Tian,Yangchen Liu,Yongqian Shu,Yingrui Fan,Li Wang,Juan Li,Jie Ding,Yifan Lian

doi:10.1186/s12943-015-0318-0

Abstract

BackgroundLong noncoding RNAs (lncRNAs) have emerged recently as a new class of genes that regulate cellular processes, such as cell growth and apoptosis. The SPRY4 intronic transcript 1 (SPRY4-IT1) is a 708-bp lncRNA on chromosome 5 with a potential functional role in tumorigenesis. The clinical significance of SPRY4-IT1 and the effect of SPRY4-IT1 on cancer progression are unclear.MethodsQuantitative reverse transcriptase PCR (qRT-PCR) was performed to investigate the expression of SPRY4-IT1 in 48 breast cancer tissues and four breast cancer cell lines. Gain and loss of function approaches were used to investigate the biological role of SPRY4-IT1 in vitro. Microarray bioinformatics analysis was performed to identify the putative targets of SPRY4-IT1, which were further verified by rescue experiments, and by western blotting and qRT-PCR.ResultsSPRY4-IT1 expression was significantly upregulated in 48 breast cancer tumor tissues comparedwith normal tissues. Additionally, increased SPRY4-IT1 expression was found to be associated with a larger tumor size and an advanced pathological stage in breast cancer patients. The knockdown of SPRY4-IT1 significantly suppressed proliferation and caused apoptosis of breast cancer cells in vitro. Furthermore, we discovered that ZNF703 was a target of SPRY4-IT1 and was downregulated by SPRY4-IT1 knockdown. Moreover, we provide the first demonstration that ZNF703 plays an oncogenic role in ER (−) breast carcinoma cells.ConclusionsSPRY4-IT1 is a novel prognostic biomarker and a potential therapeutic candidate for breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0318-0) contains supplementary material, which is available to authorized users.

Highlights

Long noncoding Ribonucleic Acid (RNA) have emerged recently as a new class of genes that regulate cellular processes, such as cell growth and apoptosis
Recent studies have demonstrated that a class of nonprotein-coding RNAs, which are known as long non-coding RNAs, participates in cell fate determination and human disease pathogenesis [6,7,8,9]. Long noncoding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that are not translated into proteins [10,11]
These analyses demonstrate that SPRY4-IT1 may be a potential prognostic biomarker for breast cancer patients

Summary

Introduction

Long noncoding RNAs (lncRNAs) have emerged recently as a new class of genes that regulate cellular processes, such as cell growth and apoptosis. Despite the improved prognosis of breast cancer patients because of early diagnosis, radical surgery and the development of adjuvant therapy, breast cancer remains the most common type of cancer among women [1,2]. Traditional prognostic markers, such as the estrogen receptor (ER), progesterone receptor (PR), HER2/NEU, and p53 [3,4], are insufficient indicators of tumor aggressiveness and do not adequately discriminate between different biological and clinical outcomes [5]. Our previous studies have shown that patients with higher lncRNA Loc554202 expression present an advanced pathological breast cancer stage [19]

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Conclusion