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Mucin 16 Promotes Colorectal Cancer Development and Progression Through Activation of Janus Kinase 2

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Abstract

Background

Mucin 16 (MUC16), a cell surface-associated mucin, has been implicated to be upregulated in a large repertoire of malignances. However, its function in the pathogenesis of colorectal cancer (CRC) is unknown.

Aims

Here, we explored the regulatory role of MUC16 in CRC.

Methods

First, tumor and paracancerous tissues, and serum samples from 162 CRC patients, peripheral blood samples from 48 healthy volunteers and 72 benign colorectal patients were collected. The correlation between the MUC16 expression and the clinical phenotypes of the patients was analyzed. Subsequently, HCT116 and SW480 cells with deletion of MUC16 were established to detect changes in the growth and metastatic capacities of CRC cells. The genes with the highest correlation with MUC16 were predicted by bioinformatics, and their binding relationships were detected by Co-IP and double-labeled immunofluorescence, followed by functional rescue experiments.

Results

Overexpression of MUC16 in CRC patients was positively correlated with serum biomarkers and poor prognosis of patients. It was demonstrated by in vitro and in vivo experiments that knocking-down the expression of MUC16 could significantly inhibit the growth and metastasis of CRC cells. MUC16 activated janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) by interacting with JAK2. Further overexpression of JAK2 in cells with poor expression of MUC16 revealed a significant increase in the proliferative and metastatic capacities of CRC cells.

Conclusions

MUC16 contributes to the development and progression of CRC by binding to JAK2, thereby promoting phosphorylation of JAK2 and further activating STAT3 phosphorylation.

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Acknowledgments

The authors would like to thank the National Clinical Key Specialty Construction Project (2013-544), the Anhui Natural Science Foundation Project (1408085MKL70) and the grants of the Scientific Research of BSKY (XJ201935).

Funding

This work was supported by the National Clinical Key Specialty Construction Project (2013–544), the Anhui Natural Science Foundation Project (1408085MKL70) and the grants of the Scientific Research of BSKY (XJ201935).

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Authors and Affiliations

  1. Department of General Surgery, Anhui Provincial Hospital, Cheeloo College of Medicine, Shandong University, No. 27, Shanda South Road, Jinan, 250012, Shandong, People’s Republic of China

    Zhining Liu & Qiang Huang

  2. Department of General Surgery, The Second Hospital of Anhui Medical University, Hefei, 230601, Anhui, People’s Republic of China

    Zhining Liu, Lianbang Zhou, Xiaohu Cheng, Heng Jiang, Yang Huang, Yingfeng Zhang & Tongtong Xu

  3. Department of Emergency ICU, The First Affiliated Hospital of Anhui Medical University, Hefei, 230000, Anhui, People’s Republic of China

    Yimei Gu

  4. Department of Molecular Pathology, Guangzhou Daan Clinical Testing Center Co., Ltd, Guangzhou, 510000, Guangdong, People’s Republic of China

    Xianghua Li

  5. Department of Nutrition, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China

    Wanshui Yang

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  1. Zhining Liu
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  2. Yimei Gu
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Contributions

ZNL is the guarantor of integrity of the entire study and contributed to the concepts; YMG and XHL contributed to the design and definition of intellectual content of this study; LBZ, XHC, HJ, YH and YFZ contributed to the experimental studies, data acquisition and statistical analysis; TTX, WSY and QH contributed to the source, validation and methodology. All authors contributed to the manuscript preparation, read and approved the final manuscript.

Corresponding author

Correspondence to Qiang Huang.

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Conflicts of interest

The authors declare no potential conflicts of interest.

Ethics approval

The research was permitted by the Ethics Committee of the Second Hospital of Anhui Medical University, and was in accordance with the Declaration of Helsinki. All participants involved in this study signed an informed consent. All animal experiments were performed in accordance with the institutional guidelines and were approved by the Laboratory Animal Center of the Second Hospital of Anhui Medical University.

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Liu, Z., Gu, Y., Li, X. et al. Mucin 16 Promotes Colorectal Cancer Development and Progression Through Activation of Janus Kinase 2. Dig Dis Sci 67, 2195–2208 (2022). https://doi.org/10.1007/s10620-021-07004-3

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  • DOI: https://doi.org/10.1007/s10620-021-07004-3

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