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miR-196a-5p Correlates with Chronic Atrophic Gastritis Progression to Gastric Cancer and Induces Malignant Biological Behaviors of Gastric Cancer Cells by Targeting ACER2

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Abstract

Background

As the prognosis of early gastric cancer (EGC) is significantly better than that of advanced gastric cancer (AGC), the development of biomarkers to monitor the progression of chronic atrophic gastritis (CAG) to gastric cancer (GC) is essential.

Methods

Stomach tissue miRNA and mRNA sequences from patients with chronic non-atrophic gastritis (CNAG), CAG, precancerous lesions of gastric cancer (PLGC), and GC were analyzed. A publicly available GC-related miRNA microarray dataset was obtained from the Gene Expression Omnibus database. Spearman’s correlation and differential gene analyses, and clinical validation were used to identify novel miRNAs correlating with CAG progression to GC. miRNA targets were predicted using weighted gene co-expression analysis and databases. A dual-luciferase reporter assay was performed to check for direct interaction between miR-196a-5p and ACER2. The CCK-8 and wound healing assays, and flow cytometry were performed to evaluate cell proliferation, migration, and apoptosis.

Results

miR-196a-5p was correlated with CAG progression to GC. Overexpression of miR-196a-5p promoted GC cell proliferation and migration and inhibited apoptosis, whereas suppression of miR-196a-5p exerted the opposite effect. Based on the prediction and luciferase assays, ACER2 was identified as the target of miR-196a-5p. ACER2 was downregulated in GC cell lines. Knockdown of ACER2 increased GC cell proliferation rates and migration ability and inhibited apoptosis, while ACER2 overexpression led to the opposite effect.

Conclusions

miR-196a-5p correlated with CAG progression to GC and induced malignant biological behaviors of GC cells by targeting ACER2, providing a novel monitoring biomarker and target for GC prevention.

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Data Availability

The datasets used and/or analyzed during the current study are available from the Gene Expression Omnibus database (GSE93415) and the NCBI Sequence Read Archive with project numbers SRP234371 and SRP234584.

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Acknowledgements

None declared.

Funding

This study was supported by the National Natural Science Foundation (No. 82104602, 81973819, 81904139 and 81904145), Collaborative Innovation Team Project of First-Rate Universities and Disciplines and High-level University Discipline of Guangzhou University of Chinese Medicine (No. 2021xk47), Natural Science Foundation of Guangdong Province (No. 2019A1515011145), Guangdong Medical Science and Technology Research Fund (Nos. B2021089, A2020186), Guangzhou Science and Technology Project (No. 202102020535), Clinical Research Project of Innovation Hospital in the First Affiliated Hospital of Guangzhou University of Chinese Medicine (No. 2019IIT19), and Innovation Development Project of the First Affiliated Hospital of Guangzhou University of Chinese Medicine (No. 2019QN01).

Author information

Author notes

  1. Junhui Zheng and Xiaotao Jiang are co-first authors and contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China

    Junhui Zheng, Xiaotao Jiang, Yanhua Yan, Fengbin Liu, Yi Wen & Peiwu Li

  2. First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China

    Junhui Zheng, Xiaotao Jiang & Yanhua Yan

  3. Department of Gastroenterology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Kailin Jiang

  4. Department of Gastroenterology, Hainan Provincial Hospital of Traditional Chinese Medicine, Haikou, 570100, Hainan, China

    Jinglin Pan

  5. Baiyun Hospital of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510470, Guangdong, China

    Fengbin Liu

  6. Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China

    Fengbin Liu

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Contributions

FL, YW, and PL designed this study. XJ, KJ, and JZ performed the experiments and wrote the manuscript. YY and JP coordinated the study and interpreted the results. KJ collected data. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Peiwu Li.

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Ethical Approval and Consent to Participate

All patients signed an informed consent form before the operation. This study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine.

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Zheng, J., Jiang, X., Jiang, K. et al. miR-196a-5p Correlates with Chronic Atrophic Gastritis Progression to Gastric Cancer and Induces Malignant Biological Behaviors of Gastric Cancer Cells by Targeting ACER2. Mol Biotechnol 65, 1306–1317 (2023). https://doi.org/10.1007/s12033-022-00589-8

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