Keming Wang¹, Yongguo Shi²

¹Department of Oncology,Second Affiliated Hospital, Nanjing Medical University, ²Department of Oncology,Nanjing Medical University

Objective:Long noncoding RNAs (lncRNAs) comprises agroup of RNA molecules defined as transcripts longer than 200 nucleotides thatlack protein coding potential. Evidence is growing that lncRNAs are importantregulatory molecules involved in various cellular processes, such as cellgrowth and apoptosis. Recently, a series of assays were performed to understandthe role of an intronic transcript 1 (SPRY4-IT1), a 708-bp lncRNA, becauseSPRY4-IT1 expression was elevated in cancer tissues and cell lines, andSPRY4-IT1 levels were highly positively correlated with tumorigenesis. However,investigation of the tumorigenic effects of SPRY4-IT1 on breast cancer is stillin its infancy. Method: Quantitative reverse transcriptase PCR (qRT-PCR)wasperformed to investigate the expression of SPRY4-IT1 in 48 breast cancertissues and four breast cancer cell lines. Gain and loss of function approacheswere used to investigate the biological role of SPRY4-IT1 in vitro. Microarraybioinformatics analysis was performed to identify the putative targets ofSPRY4-IT1, which were further verified by rescue experiments, and by westernblotting and qRT-PCR. Result: SPRY4-IT1 expression was significantlyupregulated in 48 breast cancer tumor tissues compared with normal tissues.Additionally, increased SPRY4-IT1 expression was found to be associated with alarger tumor size and an advanced pathological stage in breast cancer patients.The knockdown of SPRY4-IT1significantly suppressed proliferation and causedapoptosis of breast cancer cells in vitro. Furthermore, we discoveredthatZNF703was a target of SPRY4-IT1 and was down regulated by SPRY4-IT1 knockdown.Moreover, we provide the first demonstration hat ZNF703 plays an oncogenic rolein ER (-) breast carcinoma cells. Conclusion: Compared withparacancerous, SPRY4-IT1 expression was elevated in breast cancer tissues andderegulated SPRY4-IT1 can be important drivers of malignant transformation.Moreover, the tumorigenic effects of SPRY4-IT1 were partially mediated by theregulation of certain target gene ZNF703. Our data suggest that SPRY4-IT1 playsa critical role in breast cancer tumorigenesis and may represent a novelprognostic marker and potential therapeutic target in patients with breastcancer.

Key Words: the long noncoding RNASPRY4IT1 proliferation