The long noncoding RNA SPRY4-IT1 increases the proliferation of human breast cancer cells by upregulating ZNF703 expression.
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.
Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China. 1138303166@qq.com.|Taixing People's Hospital, Taixing, Jiangsu, PR China. 1138303166@qq.com.
Yongguo
Y
Shi
Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China. lijuan123@163.com.
Juan
J
Li
Taixing People's Hospital, Taixing, Jiangsu, PR China. liuyctx@163.com.
Yangchen
Y
Liu
Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China. 430397952@qq.com.
Jie
J
Ding
Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China. yingrui668@163.com.
Yingrui
Y
Fan
Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China. 82560036@qq.com.
Yun
Y
Tian
Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China. 911165@qq.com.
Li
L
Wang
Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China. Yifan23@sohu.com.
Yifan
Y
Lian
Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China. kemingwang@njmu.edu.cn.
Keming
K
Wang
Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China. shuyongqian@csco.org.cn.
Yongqian
Y
Shu
D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D061986:MCF-7 Cells; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics*
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D062085:RNA, Long Noncoding; C499038:SPRY4 protein, human; C541016:ZNF703 protein, human