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High level of ANO1 promotes pancreatic cancer growth in concert with oncogenic KRAS

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Abstract

Background

Anoctamin-1 (ANO1) was identified as an unfavorable prognostic marker in pancreatic cancer. However, the exact implication of ANO1 in pancreatic cancer is still poorly understood. Here we investigated the effect of ANO1 in pancreatic cancer progression under the context of oncogenic KRAS, aiming at finding a new therapeutic target.

Methods

Knockdown and overexpression of oncogenic KRAS as well as ANO1 in PDAC cell lines were performed by lentivirus infection. Cell proliferation and migration assay, RNA seq analysis were performed in PDAC cells bearing different status of ANO1 and KRAS. In vivo mice model was used to investigate the xenograft tumor growth with different status of KRAS and ANO1.

Results

Our results showed that ANO1 expression level is elevated in poorly differentiated cancer cells. Overexpression of ANO1 in PDAC cancer cells was found to promote cancer cell proliferation in vitro and in vivo, which synergized with the introduction of oncogenic KRAS. Consistently, knockdown of ANO1 expression was found to suppress cancer growth in vitro and in vivo. RNA seq analysis revealed that the observed synergistic cancer-promoting effect from ANO1 and oncogenic KRAS is likely due to concurrent activating key genes involved in lipid metabolism including HMGCS1.

Conclusion

The outcome from our study suggests that ANO1 plays an important role in promoting pancreatic cancer development, especially at the presence of oncogenic KRAS. Considering the prevalence of KRAS mutation in pancreatic cancer patients, suppression ANO1 may represent a potential effective therapeutic measure in pancreatic cancer treatment.

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Data availability

Original sequencing data from this study was submitted to GEO database with accession# GSE202825. The dataset will be public available upon the acceptance of our manuscript for publication.

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Funding

This work was supported by the National Natural Science Youth Fund of the People’s Republic of China (Grant No. 81601234), the Science and Technology Research Project of Jilin Provincial Education Department (Grant Nos. JJKH20210484KJ and JJKH20210500KJ), the Health Science and Technology Innovation Project of Jilin Province (Grant No. 20192C005), the Science and Technology Planning Project of Jilin Province (Grant No. 20200404099YY).

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Authors and Affiliations

  1. Department of Human Anatomy and Histology-Embryology, School of Basic Medical Sciences, Xi’an Jiaotong University, Xi’an, 710061, China

    Lei Zhang & Yihua Qian

  2. Department of Biotechnology, College of Laboratory Medicine, Jilin Medical University, Jilin, 132013, China

    Lei Zhang, Hao Wang, Jian Guo, Huijing Xu & Meiyan Sun

Authors
  1. Lei Zhang
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  2. Hao Wang
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  3. Jian Guo
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  4. Huijing Xu
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  5. Yihua Qian
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  6. Meiyan Sun
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Contributions

LZ contributed to data collection, analysis and manuscript preparation. HW and JG contributed to data collection and interpretation. HX contributed to data collection and analysis. YQ and MS contributed to study conception and design, manuscript preparation, as well as funding resources.

Corresponding authors

Correspondence to Yihua Qian or Meiyan Sun.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

All animal experiments were performed by following the experimental ethical guideline issued by Jilin Medical University with an approved permit No. 2019_WJW_004.

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Zhang, L., Wang, H., Guo, J. et al. High level of ANO1 promotes pancreatic cancer growth in concert with oncogenic KRAS. Mol Biol Rep 50, 3297–3307 (2023). https://doi.org/10.1007/s11033-023-08293-9

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  • DOI: https://doi.org/10.1007/s11033-023-08293-9

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