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The inhibitory effect of LINC00261 upregulation on the pancreatic cancer EMT process is mediated by KLF13 via the mTOR signaling pathway

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Abstract

Purpose

The long noncoding RNA LINC00261 was reported to be involved in carcinogenesis and has been validated as a tumor suppressor in pancreatic cancer (PC); however, how LINC00261 is regulated has not been fully examined. Here, we attempted to investigate the upstream and downstream targets of LINC00261 in PC.

Methods

LINC00261 expression in PC tissues was examined by the Gene Expression Omnibus (GEO) datasets and the Gene Expression Profiling Interactive Analysis (GEPIA) database. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays were performed to detect the expression level of LINC00261 in PC cells. The location of LINC00261 in PC cells was identified by RNA fluorescence in situ hybridization (RNA-FISH). Cell Counting Kit-8 (CCK-8), cell apoptosis assay, transwell invasion and migration assays testified the critical role of LINC00261 in PC. The luciferase reporter assay was applied to confirm the binding of LINC00261 to its upstream transcription factor KLF13. The changes in LINC00261 related target protein levels were analyzed by Western blotting assay.

Results

LINC00261 was significantly lower in PC tissues and was mainly concentrated in the nucleus. Overexpression of LINC00261 inhibited the invasion and migration of PC cells. Mechanistically, transcription factor KLF13 was confirmed to inhibit the epithelial-mesenchymal transition (EMT) process of PC cells by promoting the transcription of LINC00261 and suppressing the expression of metastasis-associated proteins, such as matrix metalloproteinase MMP2 and vimentin, thus inhibiting the metastasis of PC.

Conclusion

LINC00261 regulates PC cell metastasis through the “KLF13-LINC00261-mTOR-P70S6K1-S6” signaling pathway, which provides a significant set of potential PC therapeutic targets.

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Availability of data and materials

The data and materials are available from the corresponding author on request.

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Funding

This work was funded by the National Key Research and Development Program of China (2018YFA0902000); the fellowship of China postdoctoral science foundation (2020T130723); the Basic Scientific Research Business Expense Project of China Pharmaceutical University (No. 2632021ZD07); a Project Funded by the Priority Academic Program Development (PADP) of Jiangsu Higher Education Institutions.

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Author notes

  1. B. Li and S. Pang Contributed equally.

Authors and Affiliations

  1. Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, P.R. China

    B. Shen & Y. Zhou

  2. School of Life Science and Technology, China Pharmaceutical University, Jiangsu, 211198, P.R. China

    B. Li, S. Pang, J. Dou & C. Zhou

  3. Institute of Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiaotong University, Shanghai, 200025, P.R. China

    B. Shen & Y. Zhou

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  1. B. Li
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  4. C. Zhou
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  6. Y. Zhou
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Contributions

BPL, SYP and YRZ initiated the study, and conceived and performed the experiments. JD contributed to the data analysis. CLZ and BYS contributed to the conception of the study and assisted with data interpretation. All authors approved the final manuscript.

Corresponding authors

Correspondence to B. Shen or Y. Zhou.

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Li, B., Pang, S., Dou, J. et al. The inhibitory effect of LINC00261 upregulation on the pancreatic cancer EMT process is mediated by KLF13 via the mTOR signaling pathway. Clin Transl Oncol 24, 1059–1072 (2022). https://doi.org/10.1007/s12094-021-02747-x

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  • DOI: https://doi.org/10.1007/s12094-021-02747-x

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