Abstract
Breast cancer (BC) threatened the life health of a tremendous amount of the population, and the estimated number of death is still rising nowadays. We found that stress-induced phosphoprotein 1 (STIP1) is overexpressed in BC tissues compared to non-tumorous breast tissues. Our study is to validate the prognostic value of STIP1 and investigate its biological role in BC. We verified the upregulation of STIP1 in multiple databases, proved that STIP1 is upregulated in BC tissues and cell lines using real-time quantitative PCR (qRT-PCR). We used small interfering RNA to examine the function of STIP1 in BC cell lines (BT-549, MDA-MB-231, Hs-578 T) and explored the mechanism of function of STIP1 in BC cells using Western blotting and qRT-PCR. Analyses of multiple databases indicated that high STIP1 expression is a marker that effectively distinguishes BC patients from healthy control and predicts worse clinical outcomes in BC. The loss-of-function experiments showed that STIP1 silencing results in inhibition of cell proliferation and migration, inducing cell apoptosis, and S-phase arrest in vitro. Our study also showed that STIP1 downregulation inhibited the JAK2/STAT3 pathway and epithelial-mesenchymal transition process. Rescue experiments demonstrated that the oncogenic effect of STIP1 is partially dependent on mediating JAK2 expression. This study verified that STIP1 is an oncogenic gene that promotes BC progression and serves as a valuable diagnostic and outcome-related marker of BC.
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Funding
This study was funded by the National Natural Science Foundation of China (No. 81572291), the Natural Science Foundation of Zhejiang Province (LGF18H160031, LY18H160053), and the Science And Technology Project of Wenzhou (Y20190204, Y20170740).
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LL and JW wrote the manuscript. JW and BL did the main experiments. EX and CZ analyzed the raw data. YW and LY revised the manuscript. YC and OW designed and funded the whole work.
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Lin, L., Wen, J., Lin, B. et al. Stress-induced phosphoprotein 1 facilitates breast cancer cell progression and indicates poor prognosis for breast cancer patients. Human Cell 34, 901–917 (2021). https://doi.org/10.1007/s13577-021-00507-1
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DOI: https://doi.org/10.1007/s13577-021-00507-1