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The long noncoding RNA colon cancer-associated transcript-1/miR-490 axis regulates gastric cancer cell migration by
Baoguo Zhou1, Yuli Wang1, Jinpeng Jiang1
1Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Abstract:
Colon cancer-associated transcript-1 (CCAT1) is a highly conserved long noncoding RNA that is deregulated in several cancers. However, its role in gastric carcinoma and its post-transcriptional regulation remain poorly understood. In this study, we provide the first evidence that CCAT1 regulates miR-490 in gastric cancer (GC) cells. Interestingly, miR-490 can also repress CCAT1 expression. CCAT1 expression was significantly upregulated, and miR-490 expression was downregulated in GC. The negative correlation between miR-490 and CCAT1 expression was observed in GC tissues. Importantly, CCAT1 contains a putative miR-490-binding site, and deletion of this binding site abolishes their miR-490 responsiveness. Post-transcriptional CCAT1 silencing by miR-490 significantly suppressed GC cell migration. Furthermore, miR-490 directly bound to the hnRNPA1 mRNA 3'-UTR to repress its translation. Inhibition of miR-490 rescued CCAT1 siRNA-mediated suppression of cell migration. hnRNPA1 expression was significantly upregulated in GC specimens, and there was a negative correlation between miR-490 and hnRNPA1 expression and also a positive correlation between hnRNAP1 expression level and CCAT1 level. Taken together, we show for the first time that the CCAT1/miR-490/hnRNPA1 axis promotes GC migration, and it may have a possible diagnostic and therapeutic potential in GC.
Insights
Colon cancer-associated transcript-1 (CCAT1) regulates miR-490 in gastric cancer (GC) cells, promoting tumor cell migration. This CCAT1/miR-490/hnRNPA1 axis presents potential diagnostic and therapeutic targets for GC.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Colon cancer-associated transcript-1 (CCAT1) is a long noncoding RNA implicated in various cancers.
- Its specific role and regulation in gastric carcinoma (GC) remain largely unclear.
Purpose of the Study:
- To investigate the regulatory relationship between CCAT1 and miR-490 in GC.
- To elucidate the functional impact of this interaction on GC cell migration.
Main Methods:
- Expression analysis of CCAT1 and miR-490 in GC cell lines and tissues.
- Luciferase reporter assays to confirm the binding site and regulatory interaction.
- Cell migration assays following CCAT1 or miR-490 manipulation.
- Analysis of hnRNPA1 expression and its correlation with CCAT1 and miR-490.
Main Results:
- CCAT1 was significantly upregulated, while miR-490 was downregulated in GC.
- CCAT1 and miR-490 exhibited a negative correlation in GC tissues.
- miR-490 directly targeted CCAT1 and suppressed GC cell migration.
- miR-490 also repressed hnRNPA1 translation, and hnRNPA1 was upregulated in GC.
- Inhibition of miR-490 reversed CCAT1 siRNA-induced suppression of cell migration.
Conclusions:
- The CCAT1/miR-490/hnRNPA1 axis promotes gastric cancer cell migration.
- This axis represents a potential diagnostic biomarker and therapeutic target for GC.
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