Study of the regulatory network of MUC1 and tumor-associated proteins

doi:10.3969/j.issn.1674-8115.2022.08.007

Abstract

Abstract:

Objective ·To investigate the level of the expression of mucin 1 (MUC1) in different cancers and its impact on patient survival, and predict the possible mechanisms of MUC1 involvement in oncogenesis and tumor progression by analyzing the regulatory network of tumor-associated proteins that interact with MUC1. Methods ·The mRNA levels of MUC1 in 33 tumors and the relationship between the expression of MUC1 and patient survival were analyzed by using the GEPIA 2 online platform. MUC1-HA plasmids were transfected in HEK293T cells, and then MUC1-binding proteins were obtained by co-immunoprecipitation (Co-IP) experiments with HA antibody, which was later analyzed by liquid chromatography-tandem mass spectrometry (LCMS/MS). The subcellular localization, molecular function, diseases involved, biological process of MUC1-binding proteins and the regulatory network of interactions between these proteins were analyzed by using String 11.5 online platform. Results ·MUC1 was highly expressed in 9 kinds of tumors, including breast cancer, cervical cancer, diffuse large B-cell tumor, glioblastoma multiforme, brain lower grade glioma, ovarian carcinoma, pancreatic carcinoma, thymoma, and uterine corpus carcinoma. The relationship between MUC1 expression and overall survival in these 9 kinds of tumors was analyzed, and MUC1 expression was found to be negatively correlated with the overall survival. Higher MUC1 expression was related to significantly shorter survival time in 6 kinds of tumors, including breast cancer, cervical cancer, glioblastoma multiforme, brain lower grade glioma, pancreatic carcinoma, and thymoma. A total of 526 MUC1-binding proteins were detected by mass spectrometry analysis, and these proteins were mostly localized in organelles, cytoplasm, and membrane structures. The main molecular functions of these proteins included protein binding, ion binding, and enzymatic activity. They were primarily involved in anatomical entity diseases, cell proliferation diseases, metabolic diseases, and cancers. The related biological processes largely consisted of cellular stress, metabolism, development, and biosynthesis. MUC1-binding proteins played various roles in signaling pathways of metabolism, cancer, cGMP-cGMP-dependent protein kinase (PKG), tumor necrosis factor (TNF), and cell cycle. Further analysis of MUC1-binding-protein-associated signaling pathways revealed that they were heavily implicated in cancer-related signaling pathways such as Wnt/β-catenin, Notch, and cAMP on the one hand, and promoted tumor development by regulating metabolism, apoptosis, and cell cycle on the other hand. Conclusion ·MUC1 is highly expressed in a variety of tumor issues and is associated with poor prognosis of patients. MUC1 regulates cellular metabolism and plays a part in tumor-related signaling pathways possibly through protein interactions. This study innovatively identifies several new MUC1-binding proteins, which lay the foundation for further investigation of new biological functions of MUC1.

Key words: mucin 1 (MUC1), tumor, survival analysis, proteome, signaling pathway

CLC Number:

CHU Yunkai, LIAO Chunhua, DENG Huayun, HUANG Lei. Study of the regulatory network of MUC1 and tumor-associated proteins[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(8): 1024-1033.

Figures/Tables 5

Fig 1 Transcription levels of MUC1 in different tumor tissues

Fig 2 Relationship between MUC1 expression and OS in 9 kinds of cancers

Fig 3 Subcellular localization and molecular function of MUC1-binding proteins

Fig 4 Diseases, biological processes and signaling pathways associated with MUC1-binding proteins

Fig 5 Signaling pathways of MUC1-binding proteins

TrendMD

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