LncRNA UCA1 promotes tumor metastasis by inducing miR-203/ZEB2 axis in gastric cancer

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.

lncRNA CERS6‐AS1 as ceRNA promote cell proliferation of breast cancer by sponging miR‐125a‐5p to upregulate BAP1 expression

“…Yang et al 32 found lncRNA FTX promoted colorectal cancer progression via sponge miR‐215. Gong et al 33 observed that lncRNA UCA1 acted as a ceRNA to regulate expression of ZEB2 in gastric cancer. However, as an emerging lncRNA, the biological function of CERS6‐AS1, especially in breast cancer, is still unclear.…”

Crosstalk between the lncRNA UCA1 and microRNAs in cancer

“…UCA1 could significantly promote cell migration and inhibit apoptosis in GC cell lines SUN-216 and SGC-7091 via inhibition of miR-182, whose downstream target is tissue inhibitors of metalloproteinase 2 (TIMP2) [63]. Similarly, UCA1 enhanced the invasion of GC by directly interacting with miR-203 or miR-7-5p, increasing the release of miR-203-targeted transcripts zinc finger E-box-binding homeobox2 (ZEB2) or miR-7-5p-targeted epidermal growth factor receptor (EGFR), respectively [64,65]. Moreover, UCA1 also could promote the proliferation and invasion of GC through sponging miR-495-3p [30].…”

LncRNA IGFL2‐AS1 functions as a ceRNA in regulating ARPP19 through competitive binding to miR‐802 in gastric cancer

“…Several lncRNAs have been documented to participate in various biological processes, especially in tumorigenesis 6–8 . Multiple lncRNAs have been reported to regulate cell proliferation, migration, invasion, and apoptosis in GC cells, such as GHET1, HOTAIR, UCA1, and CASC15 among others 9–12 . LncRNAs can act as oncogenes or tumor suppressors in GC.…”

“…[6][7][8] Multiple lncRNAs have been reported to regulate cell proliferation, migration, invasion, and apoptosis in GC cells, such as GHET1, HOTAIR, UCA1, and CASC15 among others. [9][10][11][12] LncRNAs can act as oncogenes or tumor suppressors in GC.…”