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IFN-γ affects pancreatic cancer properties by MACC1-AS1/MACC1 axis via AKT/mTOR signaling pathway

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Abstract

Background

Metastasis-related in colon cancer 1 (MACC1) is highly expressed in a variety of solid tumours, but its role in pancreatic cancer (PC) remains unknown. Interferon gamma (IFN-γ) affecting MACC1 expression was explored as the potential mechanism following its intervention.

Methods

Expressions of MACC1 treated with IFN-γ gradient were confirmed by quantitative real-time PCR (qRT-PCR) and western blot (WB). Proliferation, migration, and invasion abilities of PC cells treated with IFN-γ were analysed by CCK8, EDU, colony formation, Transwell (with or without matrix gel) and wound-healing assays. Expression of antisense long non-coding RNA of MACC1, MACC1-AS1, and proteins of AKT/mTOR pathway, (pho-)AKT, and (pho-)mTOR was also assessed by qRT-PCR and WB. SiRNA kit and lentiviral fluid were conducted for transient expression of MACC1 and stable expression of MACC1-AS1, respectively. Rescue assays of cells overexpressing MACC1-AS1 and of cells silencing MACC1 were performed and cellular properties and proteins were assessed by the above-mentioned assays as well.

Results

IFN-γ inhibited MACC1 expression in a time- and dose-dependent manner; 100 ng/mL IFN-γ generally caused downregulation of most significant (p ≤ 0.05). In vitro experiments revealed that IFN-γ decreased cellular proliferation, migration, and invasion abilities and downregulated the expression of pho-AKT and pho-mTOR (p ≤ 0.05). Conversely, overexpression of MACC1-AS1 upregulated pho-AKT and pho-mTOR proteins, and reversed cellular properties (p ≤ 0.05). Rescue assays alleviated the above changes of pho-AKT/ mTOR and cellular properties.

Conclusion

IFN-γ affected PC properties by MACC1-AS1/MACC1 axis via AKT/mTOR signaling pathway, which provides novel insight for candidate targets for treating PC.

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Data availability

The datasets analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank for the help of Key laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University) and Research Institute of Innovative Think-tank in Guangxi Medical University (The gene–environment interaction in hepatocarcinogenesis in Guangxi HCCs and its translational applications in the HCC prevention).

Funding

This work has been financially supported by the National Natural Science Foundation of China (Grant Nos. 31560257 and 81960439), the “139” Plan for Training High Level Cadre Talents in Guangxi Medicine (G201903004).

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  1. Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China

    X.-Y. Shi, X.-L. Zhang, Q.-Y. Shi, X. Qiu, X.-B. Wu, B.-L. Zheng, H.-X. Jiang & S.-Y. Qin

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X-YS, and S-Y Qin designed this study. X-YS wrote this manuscript and S-Y Qin guided the revision of the manuscript and submitted for publication. All of the authors conducted the study, and approved the final report.

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Shi, XY., Zhang, XL., Shi, QY. et al. IFN-γ affects pancreatic cancer properties by MACC1-AS1/MACC1 axis via AKT/mTOR signaling pathway. Clin Transl Oncol 24, 1073–1085 (2022). https://doi.org/10.1007/s12094-021-02748-w

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