NOTCH3 inhibits transcription factor ZEB1 expression and metastasis of breast cancer cells via transcriptionally upregulating miR-223

Chen, Wen-Jia; Zhong, Hui-Ting; Wu, Hua-Tao; Hou, Yan-Yu; Wu, Zheng; Fang, Ze-Xuan; Liu, Jing

doi:10.7150/jca.89034

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J Cancer 2024; 15(1):192-203. doi:10.7150/jca.89034 This issue Cite

Research Paper

NOTCH3 inhibits transcription factor ZEB1 expression and metastasis of breast cancer cells via transcriptionally upregulating miR-223

Wen-Jia Chen^1,2,#, Hui-Ting Zhong^3,#, Hua-Tao Wu^4,#, Yan-Yu Hou^1,2, Zheng Wu^1,2, Ze-Xuan Fang^1,2, Jing Liu^1,2,✉

1. The Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou 515041, China.
2. Department of Physiology/Changjiang Scholar's Laboratory, Shantou University Medical College, Shantou 515041, China.
3. Department of Breast Surgery, Huizhou Municipal Central Hospital, Huizhou 516000, China.
4. Department of General Surgery, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China.
^# These authors contributed equally.

Citation:

Chen WJ, Zhong HT, Wu HT, Hou YY, Wu Z, Fang ZX, Liu J. NOTCH3 inhibits transcription factor ZEB1 expression and metastasis of breast cancer cells via transcriptionally upregulating miR-223. J Cancer 2024; 15(1):192-203. doi:10.7150/jca.89034. https://www.jcancer.org/v15p0192.htm

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Abstract

Background: NOTCH receptor 3 (NOTCH3) and zinc finger E-box binding protein 1 (ZEB1) play important roles in breast cancer respectively. NOTCH3 maintains the luminal phenotype and inhibits epithelial-mesenchymal transition (EMT) in breast cancer, while ZEB1 and NOTCH3 have the opposite effects.

Methods: Public databases were used to predict the expression of NOTCH3 and ZEB1 in breast cancer cell lines. The regulatory effect of NOTCH3 on ZEB1 expression was verified by western blot and RT-PCR. MiRNAs regulating ZEB1 expression were identified by using multiple databases and confirmed by reporter gene experiments. Cellular function experiments were conducted to evaluate the role of NOTCH3/miR-223/ZEB1 in the proliferation and invasion of triple-negative breast cancer (TNBC).

Results: NOTCH3 and ZEB1 have opposite expression pattern in MCF-7 cells that over-express LncATB or were incubated in TGF-β to induce EMT. Western blotting and RT-PCR showed that NOTCH3 could regulate expression of ZEB1. MiR-223 inhibited the proliferation and invasion of breast cancer cells via down-regulating the expression of ZEB1. NOTCH3 inhibited the proliferation and invasion of breast cancer cells via up-regulating the expression of miR-223. Clinically, high expression of NOTCH3, miR-223 or low expression of ZEB1 were related to good prognosis of breast cancer patients.

Conclusion: The current study reports a novel NOTCH3/miR-223/ZEB1 axis, which can inhibit the proliferation and invasion of breast cancer cells, and may serve as a potential biomarker for the prognosis of breast cancer.

Keywords: NOTCH3, miR-223, ZEB1, breast cancer, metastasis

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APA

Chen, W.J., Zhong, H.T., Wu, H.T., Hou, Y.Y., Wu, Z., Fang, Z.X., Liu, J. (2024). NOTCH3 inhibits transcription factor ZEB1 expression and metastasis of breast cancer cells via transcriptionally upregulating miR-223. Journal of Cancer, 15(1), 192-203. https://doi.org/10.7150/jca.89034.

ACS

Chen, W.J.; Zhong, H.T.; Wu, H.T.; Hou, Y.Y.; Wu, Z.; Fang, Z.X.; Liu, J. NOTCH3 inhibits transcription factor ZEB1 expression and metastasis of breast cancer cells via transcriptionally upregulating miR-223. J. Cancer 2024, 15 (1), 192-203. DOI: 10.7150/jca.89034.

NLM

CSE

Chen WJ, Zhong HT, Wu HT, Hou YY, Wu Z, Fang ZX, Liu J. 2024. NOTCH3 inhibits transcription factor ZEB1 expression and metastasis of breast cancer cells via transcriptionally upregulating miR-223. J Cancer. 15(1):192-203.

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