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Downregulation of circ-STK39 suppresses pancreatic cancer progression by sponging mir-140-3p and regulating TRAM2-mediated epithelial-mesenchymal transition

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Abstract

Background

Pancreatic cancer (PC) is amongst the most lethal gastrointestinal tumors, which is the seventh leading reason of cancer-related mortality worldwide. Previous studies have indicated that circular RNAs (circRNAs), which is a new type of endogenous noncoding RNA (ncRNA), can mediate tumor progression in diverse tumor types including PC. Whereas precise roles regarding circRNAs and their underlying regulatory mechanisms in PC remain unknown.

Methods

In the current study, we employed next generation sequencing (NGS) to characterize abnormally expressed circRNAs among PC tissues. Next, we assessed expression levels of one identified circRNA, circ-STK39, in PC cell lines and tissues. Then, using bioinformatics analysis, luciferase reporter, Transwell migration, EdU and CCK-8 assays, we examined the regulatory mechanisms and targets of circ-STK39. Finally, our group explored the circ-STK39 role in PC tumor growth and metastasis in vivo.

Results

Our team discovered that circ-STK39 expression increased in PC tissues and cells, suggesting that circ-STK39 may have a role in PC progression. Downregulation of circ-STK39 inhibited PC proliferation and migration. Bioinformatics and luciferase reporter outcomes demonstrated that TRAM2 and miR-140-3p were circ-STK39 downstream targets. TRAM2 overexpression reversed the miR-140-3p overexpression effects upon migration, proliferation and the epithelial-mesenchymal transition (EMT).

Conclusion

In this regard, we showed that circ-STK39 downregulation led to decreased migration, proliferation and the EMT of PC via the miR-140-3p/TRAM2 axis.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

None.

Funding

This work was supported by grants obtained from Medical and Health Technology Plan of Zhejiang Province (2019RC179); National Natural Science Foundation of China (Grant No. 82002482); Natural Science Foundation of Zhejiang Province, Exploration Project (Grant LQ21H160034).

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Second Affiliated Hospital Zhejiang University School of Medicine, Jiefang Road No. 88, Hangzhou, Zhejiang Province, 310009, China

    Chao Li, Weifeng Liu, Zhenzhen Gao & Guogang Li

  2. Department of Pathology, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang Province, China

    Juanjuan Cai

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  1. Chao Li
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  2. Juanjuan Cai
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  3. Weifeng Liu
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Contributions

Chao Li and Guogang Li contributed to the study conception and design. All authors collected the data and performed the data analysis. All authors contributed to the interpretation of the data and the completion of figures and tables. All authors contributed to the drafting of the article and final approval of the submitted version.

Corresponding author

Correspondence to Guogang Li.

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All the authors declare that they have no conflicts of interest.

Ethics approval and consent to participate

The investigation was approved by Ethics Committee in the Second Affiliated Hospital Zhejiang University School of Medicine. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from individual participants or their relatives.

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Li, C., Cai, J., Liu, W. et al. Downregulation of circ-STK39 suppresses pancreatic cancer progression by sponging mir-140-3p and regulating TRAM2-mediated epithelial-mesenchymal transition. Apoptosis 28, 1024–1034 (2023). https://doi.org/10.1007/s10495-023-01813-9

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