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Tumor-suppressive miR-29c binds to MAPK1 inhibiting the ERK/MAPK pathway in pancreatic cancer

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Abstract

Introduction

GEO- and TCGA-based data analysis suggested the differential expression of miR-29c in pancreatic cancer. However, limited data are available on the downstream mechanistic actions of miR-29c, which may fuel the in vitro and in vivo studies of pancreatic cancer.

Methods

The downstream target gene of miR-29c and the downstream ERK/MAPK pathway involved in pancreatic cancer were predicted by bioinformatics tools. Next, the expression of miR-29c and MAPK1 was determined in pancreatic cancer tissues and cells. After ectopic expression and depletion experiments in pancreatic cancer cells, oncogenic phenotypes of pancreatic cancer cells were tested by MTS assay, Transwell assay, and flow cytometry. Effects of miR-29c/MAPK1 on tumorigenic ability in vivo were evaluated in pancreatic cancer xenografts in nude mice.

Results

Through differential analysis, five pancreatic cancer-related miRNAs (hsa-miR-29c, hsa-miR-107, hsa-miR-324-3p, hsa-miR-375, and hsa-miR-210) were screened out, among which miR-29c was selected as the key miRNA related to prognosis of pancreatic cancer patients. miR-29c could target and inhibit MAPK1 to suppress the activation of ERK/MAPK pathway. miR-29c was downregulated in pancreatic cancer, and its high expression was related to the good prognosis of pancreatic cancer patients. Both in vitro and in vivo experiments demonstrated that restoration of miR-29c inhibited oncogenic phenotypes of pancreatic cancer cells, as well as repressed tumorigenic ability of pancreatic cancer cells in nude mice.

Conclusions

Taken together, we unveil a novel miR-29c/MAPK1/ERK/MAPK axis that suppresses pancreatic cancer both in vitro and in vivo.

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Availability of data and materials

The data that support the findings of this study are available on request from the corresponding author upon reasonable request.

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Funding

This work is supported by Health Commission of Hebei Province (20220991).

Author information

Authors and Affiliations

  1. Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China

    Hongtao Si, Ning Zhang & Chang Shi

  2. The Seventh Hospital of Handan, Handan, 056005, People’s Republic of China

    Zhanjiang Luo

  3. Ninth Department of General Surgery, The Second Hospital of Hebei Medical University, No. 215, Heping West Road, Shijiazhuang, 050000, People’s Republic of China

    Senlin Hou

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  1. Hongtao Si
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Contributions

HS: conceived and designed research. NZ: performed experiments. CS: interpreted results of experiments. ZL: analyzed data. SH: prepared figures. HS and NZ: drafted paper. CS, ZL and SH: edited and revised manuscript. All authors read and approved final version of manuscript.

Corresponding author

Correspondence to Senlin Hou.

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Conflict of interests

The authors declare that they have no competing interests.

Ethics approval and consent to participate

Our study protocol was approved by the Ethics Committee of The Second Hospital of Hebei Medical University, and we collected written informed consent from all participants or their guardians. The animal experiment was also approved by the Ethics Committee of The Second Hospital of Hebei Medical University.

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Supplementary Information

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12094_2022_2991_MOESM1_ESM.jpg

Figure S1 Correlation between 5 differentially expressed miRNAs and the prognosis of pancreatic cancer patients. A, Correlation between miR-29c and prognosis of pancreatic cancer patients. B, Correlation between miR-375 and prognosis of pancreatic cancer patients. C, Correlation between miR-107 and prognosis of pancreatic cancer patients. D, Correlation between miR-324 and prognosis of pancreatic cancer patients. E, Correlation between miR-210 and prognosis of pancreatic cancer patients (JPG 1106 KB)

12094_2022_2991_MOESM2_ESM.jpg

Figure S2 Correlation between MAPK1 expression and the prognosis of pancreatic cancer patients analyzed by TCGA database. A, MAPK1 expression in pancreatic cancer tissues and normal pancreatic tissues. B, Correlation between MAPK1 at different levels and prognosis of pancreatic cancer patients (JPG 247 KB)

Supplementary file3 (DOCX 16 KB)

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Si, H., Zhang, N., Shi, C. et al. Tumor-suppressive miR-29c binds to MAPK1 inhibiting the ERK/MAPK pathway in pancreatic cancer. Clin Transl Oncol 25, 803–816 (2023). https://doi.org/10.1007/s12094-022-02991-9

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  • DOI: https://doi.org/10.1007/s12094-022-02991-9

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