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Long Non-coding RNA LINC01420 Contributes to Pancreatic Cancer Progression Through Targeting KRAS Proto-oncogene

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Abstract

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.

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Acknowledgment

We appreciate all the contributors during our study.

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Author notes

  1. Hongjun Zhai and Xinwu Zhang are co-first authors.

Authors and Affiliations

  1. Department of General Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xiwu Road, Xincheng District, Xi’an City, 710004, Shaanxi Province, China

    Hongjun Zhai, Xinwu Zhang, Xiaoli Sun, Di Zhang & Shuangyu Ma

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  1. Hongjun Zhai
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  2. Xinwu Zhang
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  3. Xiaoli Sun
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Correspondence to Xiaoli Sun.

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This article does not contain any studies with human participants performed by any of the authors. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Supplementary Fig. 1 Mechanistic investigation in SW1990 and HPAC cells.

(A) The binding of MYC protein to KRAS promoter in SW1990 and HPAC cells was validated by ChIP assay. (B) The interaction between LINC01420 and MYC protein in these two PC cells was proved by RIP assay. (C-D) ChIP assay uncovered the inhibition of LINC01420 silence on MYC occupation in KRAS promoter, (E-F) qRT-PCR result of MYC expression in SW1990 and HPAC cells under diverse transfections. * P < 0.05, ** P < 0.01. (TIFF 8015 kb)

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Zhai, H., Zhang, X., Sun, X. et al. Long Non-coding RNA LINC01420 Contributes to Pancreatic Cancer Progression Through Targeting KRAS Proto-oncogene. Dig Dis Sci 65, 1042–1052 (2020). https://doi.org/10.1007/s10620-019-05829-7

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  • DOI: https://doi.org/10.1007/s10620-019-05829-7

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