Int J Med Sci 2021; 18(14):3342-3352. doi:10.7150/ijms.62870

Research Paper

IFI30 expression predicts patient prognosis in breast cancer and dictates breast cancer cells proliferation via regulating autophagy

Yan Fan1, Xu Wang2, Yang Li3✉

1. Department of Pediatrics, The First Affiliated Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang , Liaoning, 110001 China.
2. Department of Breast Surgery, Department of Surgical Oncology, Research Unit of General Surgery, The First Affiliated Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang , Liaoning, 110001 China.
3. Department of Cell Biology, Key Laboratory of Cell Biology, National Health Commission of the PRC, and Key Laboratory of Medical Cell Biology, Ministry of Education of the PRC, China Medical University, No. 77, Puhe Road, Shenyang North New Area, Shenyang, Liaoning,110122 China.

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Citation:
Fan Y, Wang X, Li Y. IFI30 expression predicts patient prognosis in breast cancer and dictates breast cancer cells proliferation via regulating autophagy. Int J Med Sci 2021; 18(14):3342-3352. doi:10.7150/ijms.62870. Available from https://www.medsci.org/v18p3342.htm

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Abstract

Graphic abstract

Introduction: Incidence and mortality rates of breast cancer are increasing in women worldwide. Immunotherapy is a relatively popular treatment modality for all malignant tumors including breast cancer in recent years. Interferon γ-inducible protein 30 (IFI30) could catalyze the reduction of disulfide bonds and enhance major histocompatibility complex (MHC) class II-restricted antigen processing. Recent studies showed that IFI30 played an important role in the immune response of malignant tumors.

Methods: The Cancer Genome Atlas (TCGA) database and clinical proteomic tumor Analysis consortium (CPTAC) database were applied to predict the role of IFI30 in breast cancer and the relationship between IFI30 and prognosis of breast cancer patients. Then we detected the expression of IFI30 in clinical samples of breast cancer patients, and analyzed the relationship between IFI30 and the prognosis of breast cancer patients. We used lentivirus infection method to construct a stable IFI30 knockdown cell line, and detected the effect of IFI30 in breast cancer cells. Nude mice tumor bearing experiment was performed to investigate the effect of IFI30 on breast cancer cells in vivo. Western blot was used to verify the regulation of autophagy related protein LC3 and p62 by IFI30.

Results: We found that IFI30 was highly expressed in breast cancer tissues and was associated with poor outcome of patients. The knockdown of IFI30 could inhibit the proliferation, migration and invasion of breast cancer cells and significantly inhibit tumor growth in vivo. Increased accumulation of LC3-II and p62 suggested impaired autophagy in IFI30 knockdown cells.

Discussion: As a result, we suggested that IFI30 might play a key role in the initiation and progression of human breast cancer and might be a new therapeutic target in breast cancer.

Keywords: Interferon γ-inducible protein 30 (IFI30), breast cancer, cell proliferation, autophagy