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Erschienen in:
27.09.2019 | Original Article
Long Non-coding RNA LINC01420 Contributes to Pancreatic Cancer Progression Through Targeting KRAS Proto-oncogene
Erschienen in: Digestive Diseases and Sciences | Ausgabe 4/2020
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Background
Long non-coding RNAs (lncRNAs) have been increasingly uncovered to participate in multiple human cancers, including pancreatic cancer (PC). However, the underlying mechanisms of most of the lncRNAs have not been fully understood yet.
Aims
In this study, we probed the role and latent mechanism of LINC01420 in PC.
Methods
Several online tools were applied. Gene expression was evaluated by qRT-PCR or Western blot. Both in vitro and in vivo assays were conducted to probe LINC01420 function in PC. ChIP, RIP, and luciferase reporter assays were performed to determine relationships between genes.
Results
The bioinformatics analyses revealed LINC01420 was highly expressed in PC tissues. Besides, LINC01420 was pronouncedly upregulated in PC cell lines and its depletion controlled PC cell proliferation and EMT in vitro and hindered tumor growth in vivo. Importantly, KRAS was proved to mediate LINC01420-facilitated PC cell proliferation. Further, we explained that KRAS transcription was regulated by MYC, while LINC01420 enhanced the binding of MYC to KRAS promoter in the nucleus of PC cells. Intriguingly, LINC01420 boosted MYC expression in the cytoplasm of PC cells by sponging miR-494-3p.
Conclusion
This study illustrated that LINC01420 accelerates PC progression through releasing miR-494-3p-silenced MYC in cytoplasm and upregulating MYC-activated KRAS in nucleus, unveiling LINC01420 as a latent therapeutic strategy for PC patients.