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Novel circularRNA circ-0047078 promotes pancreatic ductal adenocarcinoma progression through mircoRNA miR-11181— Chemokine (C-X-C motif) Ligand 12/Melanoma Cell Adhesion Molecule/Regulator of G-protein signaling 16 pathway

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Abstract

Background

Circular RNAs (circRNAs), new members of the noncoding RNA family, have been reported to participate in various pathological conditions, especially cancer. Pancreatic ductal adenocarcinoma (PDAC), as one of the most aggressive human solid tumors, is still with a low surgical cure rate. Exploring the role of circRNAs in PDAC is meaningful, and may offer a new therapeutic approach for PDAC.

Methods and Results

Competing endogenous RNA (ceRNA) microarray revealed that circ-0047078 was highly expressed in pancreatic ductal adenocarcinoma (PDAC) tissues compared with adjacent normal tissues, and the differential expression was further confirmed by PCR in both tissues and cell lines. Cell functional assays including cell counting kit-8 (CCK-8) assay, transwell invasion assay, flow cytometry and caspase activity assay demonstrated that circ-0047078 was positively correlated with the proliferation and invasion but negatively correlated with the apoptosis of CFPAC-1 cells. Circ-0047078 knockdown led to miR-11181, CXCL12 and MCAM downregulation and RGS16 upregulation, and the effect of circ-0047078 knockdown on CFPAC-1 cell behavior change can be reversed by miR-11181 mimic. Moreover, clinicopathological analysis indicated that circ-0047078 expression level was positively correlated with lymphatic metastasis and perineural invasion. In addition, knockdown of Chemokine (C-X-C motif) Ligand 12 (CXCL12) alone decreased proliferation, invasion, but increased apoptosis of CFPAC-1 cells, and raised the activity of caspase-3, caspase-8 and caspase-9 activity. Knockdown of Melanoma Cell Adhesion Molecule (MCAM) alone decreased invasion and increased apoptosis of CFPAC-1 cells, and both caspase-3 and caspase-9 activity increased, but no obvious change observed on caspase-8, and also no significant effect on CFPAC-1 cells proliferation. Knockdown of Regulator of G-protein signaling 16 (RGS16) alone increased invasion of CFPAC-1 cells, but had no significant effect on proliferation and apoptosis, of course, no obvious change on the activity of caspase-3, caspase-8 and caspase-9 had been observed.

Conclusions

In conclusion, circ-0047078 plays a role in promoting PDAC via miR-11181 and then via CXCL12, MCAM and RGS16. Circ-0047078 may serve as a promising novel therapeutic target for PDAC patients.

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Acknowledgements

This project was supported by grants from the Daping Hospital, Army Medical University (2019CXJSA003) to Ping Chen.

Funding

This project was supported by grants from the Daping Hospital, Army Medical University (2019CXJSA003) to Ping Chen.

Author information

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Daping Hospital, Army Medical University, Chongqing, 400042, China

    Yuzhou Wang, Hangwei Fu, Bo Zhou & Ping Chen

  2. Department of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, 400038, China

    Yan Jiang

Authors
  1. Yuzhou Wang
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  2. Hangwei Fu
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  3. Yan Jiang
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  4. Bo Zhou
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  5. Ping Chen
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Contributions

All authors contributed to the study conception and design. Material preparation was performed by Yuzhou Wang, Ping Chen and Yan Jiang. Data collection and analysis were performed by Yuzhou Wang, Hangwei Fu and Bo Zhou. The first draft of the manuscript was written by Yuzhou Wang. And all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ping Chen.

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The authors declare that they have no conflict of interest.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Army Medical Center of PLA.

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Informed consent was obtained from all individual participants included in the study.

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Wang, Y., Fu, H., Jiang, Y. et al. Novel circularRNA circ-0047078 promotes pancreatic ductal adenocarcinoma progression through mircoRNA miR-11181— Chemokine (C-X-C motif) Ligand 12/Melanoma Cell Adhesion Molecule/Regulator of G-protein signaling 16 pathway. Mol Biol Rep 49, 8761–8775 (2022). https://doi.org/10.1007/s11033-022-07723-4

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  • DOI: https://doi.org/10.1007/s11033-022-07723-4

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