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

Mol Cancer. 2015 Feb 22;14:51. doi: 10.1186/s12943-015-0318-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carrier Proteins / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Down-Regulation / drug effects
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • MCF-7 Cells
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • RNA, Long Noncoding / genetics*
  • Up-Regulation / genetics*


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • RNA, Long Noncoding
  • SPRY4 protein, human
  • ZNF703 protein, human