Abstract
Increasing studies showed that long-noncoding RNAs (lncRNAs) play important roles in the biological processes, including cancer initiation and progression. However, little is known about the exact role and regulation mechanism of lncRNA UCA1 during the progression of gastric cancer (GC). In this study, we found that UCA1 was aberrantly elevated in gastric cancer tissues, and was significantly associated with lymph node metastasis and TNM stage. In vivo and in vitro, enforced UCA1 level promoted cell migration and invasion of GC cell. Depleted UCA1 expression level attenuated the ability of cell migration and invasion in GC. And then, we detected that expression level of ZEB2, a transcription factor related to tumor metastasis, was regulated by UCA1 in GC cells. miR-203 targets and suppresses to ZEB2 expression. Furthermore, we found that UCA1 could directly interact with miR-203 and lead to the release of miR-203-targeted transcripts ZEB2. Herein, we revealed the novel mechanism of UCA1 on regulating metastasis-related gene by sponge regulatory axis during GC metastasis. Our findings indicated that UCA1 plays a critical role in metastatic GC by mediating sponge regulatory axis miR-203/ZEB2. To explore function of UCA1-miR-203-ZEB2 axis may provide an informative biomarker of malignancy and a highly selective anti-GC therapeutic target.
Highlights
Gastric cancer (GC) has the fourth highest diagnosis rate and the third highest mortality among all the cancers throughout the world[1,2]
UCA1 expression level is elevated in tumor tissues of GC patients To identify the long-noncoding RNAs (lncRNAs) expression profile in GC, the Arraystar Human lncRNA Microarray was used in five paired GC and their adjacent non-tumor tissues
UCA1 is the most upregulated lncRNA analyzed by our group microarray data and two published Gene Expression Omnibus (GEO) datasets in GC
Summary
Gastric cancer (GC) has the fourth highest diagnosis rate and the third highest mortality among all the cancers throughout the world[1,2]. The lncRNA UCA1, located on the human chromosome 19p13.12, was first identified as an oncogene in bladder cancer and showed extensive regulatory functions in cell proliferation[7,8,9,10], invasion[8], metastasis[11], apoptosis[12,13,14], metabolism[15], survival[8], radiosensitivity, and chemoresistance[16,17]. These studies highlight the potential of lncRNA UCA1 as a diagnostic and prognostic biomarker and a therapeutic target in malignant tumors. Gao et al.[19] reported that
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