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High Expression of CARM1 Inhibits Lung Cancer Progression by Targeting TP53 by Regulating CTNNB1

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Objective

To explore the role of CARM1 in lung cancer (LC) and its relationship with TP53 and CTNNB1.

Methods

Lung cells H1299 and PC14 were randomly divided into six groups: ov-H1299, si-H1299, ov-PC14, si-PC14, Con-H1299, and Con-PC14. Transwell assay, plate clone formation assay, and flow cytometry were used to determine the migration, clone formation capacity, and apoptosis situation of LC cells in the six groups, respectively. Western blot assay was used to determine the protein expression of CARM1, TP53, and CTNNB1 in the six groups. CHIP assay was applied to analyze the combined characteristics of JUN and TP53 promoter. Co-immunoprecipitation was used to analyze the interaction between TP53 and CARM1/CTNNB1. Cox proportional hazard regression model was used to analyze the relevance between the expression of CARM1 and clinicopathological information of the patient. Kaplan−Meier plot was used to determine the relevance between CARM1 and patient survival.

Results

High expression of CARM1 inhibits the migration and proliferation of LC cells and promoted the apoptosis of LC cell. Overexpression of CARM1 promotes the expression of CARM1 and TP53, while decreases CTNNB1 expression. CARM1 supplementation of H1299 cells induced JUN aggregation on the TP53 promoter. TP53 and CARM1 protein/TP53 and CTNNB1 protein in H1299 cells were immunoprecipitated together. High expression of CARM1was negatively correlated with the degree of tumor metastasis. The survival period of patients with high expression CARM1 was greater than that of low expression.

Conclusion

Overexpression of CARM1 may inhibit the progression of LC by targeting TP53 via regulation CTNNB1.

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Acknowledgements

This work was supported by Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Dragon Medical Scholars (Nursery Program) of National Clinical Research Base of Traditional Chinese Medicine (No. LYTD-82) and the Zhoushan Traditional Chinese Medicine Hospital, Zhoushan Science and Technology Project (No. 2015C31036).

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Author notes

  1. Bing Hu and Xin Li are co-first authors and contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, Shanghai Minhang TCM Hospital (Shanghai Minhang Hospital of Traditional Chinese Medicine), No. 3071 HeChuan Road, Minhang District, Shanghai, 201103, China

    Bing Hu

  2. Department of Oncology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No. 725 Wanping South Road, Xuhui District, Shanghai, 200032, China

    Xin Li

  3. Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Hongkou District, Shanghai, 200437, China

    Ling Chen

  4. Department of Oncology, Zhoushan Hospital of Traditional Chinese Medicine (Zhoushan Hospital of Zhejiang University of Traditional Chinese Medicine), No. 355 Xinqiao Road, Dinghai District, Zhoushan, 316000, Zhejiang, China

    Zhongliang Liu

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  1. Bing Hu
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  2. Xin Li
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Correspondence to Zhongliang Liu.

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Hu, B., Li, X., Chen, L. et al. High Expression of CARM1 Inhibits Lung Cancer Progression by Targeting TP53 by Regulating CTNNB1. Lung 198, 415–422 (2020). https://doi.org/10.1007/s00408-020-00324-7

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  • DOI: https://doi.org/10.1007/s00408-020-00324-7

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