The Long Noncoding RNA SPRY4-IT1 Increases the Proliferation of Human Breast Cancer Cells by Upregulating ZNF703 Expression

Overview

Journal Mol Cancer

Publisher Biomed Central

Specialties Molecular Biology
Oncology

Date 2015 Mar 7

PMID 25742952

Citations 92

Authors

Yongguo Shi

Juan Li

Yangchen Liu

Jie Ding

Yingrui Fan

Yun Tian

Li Wang

Yifan Lian

Keming Wang

Yongqian Shu

Affiliations

Soon will be listed here.

Abstract

Background: Long 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.

Methods: Quantitative 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.

Results: SPRY4-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.

Conclusions: SPRY4-IT1 is a novel prognostic biomarker and a potential therapeutic candidate for breast cancer.

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