TRIM32 promotes proliferation and confers chemoresistance to breast cancer cells through activation of the NF-κB pathway

Zhao, Ting-Ting; Jin, Feng; Li, Ji-Guang; Xu, Ying-Ying; Dong, Hui-Ting; Liu, Qun; Xing, Peng; Zhu, Guo-Lian; Xu, Hao; Yin, Song-Cheng; Miao, Zhi-Feng

doi:10.7150/jca.22390

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J Cancer 2018; 9(8):1349-1356. doi:10.7150/jca.22390 This issue Cite

Research Paper

TRIM32 promotes proliferation and confers chemoresistance to breast cancer cells through activation of the NF-κB pathway

Ting-Ting Zhao¹, Feng Jin¹, Ji-Guang Li¹, Ying-Ying Xu¹, Hui-Ting Dong¹, Qun Liu¹, Peng Xing¹, Guo-Lian Zhu², Hao Xu³, Song-Cheng Yin⁴, Zhi-Feng Miao^4✉

1. Department of Breast Surgery, First Hospital of China Medical University, Shenyang, Liaoning Province, China.
2. Department of Breast Surgery, Fifth People's Hospital of Shenyang, Shenyang, Liaoning Province, China
3. Department of Medical Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
4. Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, Liaoning Province, China.

Citation:

Zhao TT, Jin F, Li JG, Xu YY, Dong HT, Liu Q, Xing P, Zhu GL, Xu H, Yin SC, Miao ZF. TRIM32 promotes proliferation and confers chemoresistance to breast cancer cells through activation of the NF-κB pathway. J Cancer 2018; 9(8):1349-1356. doi:10.7150/jca.22390. https://www.jcancer.org/v09p1349.htm

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Abstract

Dysregulation of TRIM32 has been implicated in several human cancers, however, its clinical significance and biological function in breast cancer have not been investigated. Using immunohistochemistry, we found that TRIM32 expression is upregulated in breast cancer tissues and that it correlates with advanced stage and poor prognosis. TRIM32 is also overexpressed in 4/7 breast cancer cell lines. CCK8 and colony formation assays showed that TRIM32 depletion inhibited proliferation and colony formation in the T47D cell line, while TRIM32 overexpression promoted MCF-7 cell growth and colony formation. Cell viability and Annexin V/PI staining demonstrated that TRIM32 maintained breast cancer cell survival and reduced apoptosis rate when cells were treated with cisplatin. Western blot analysis demonstrated that TRIM32 overexpression resulted in an upregulation of p-IκB, p-p65, cIAP1, and cIAP2 and a downregulation of p21 and p27 in MCF-7 cells. TRIM32 depletion in T47D cells demonstrated the opposite results, suggesting that TRIM32 may activate the NF-κB pathway. The NF-κB inhibitor BAY 11-7082 blocked the effects of TRIM32 on cisplatin resistance and cIAP1/2 protein regulation.

Taken together, the present study demonstrates that TRIM32 downregulates p21/p27 and upregulates IAP family proteins to facilitate breast cancer cell growth and inhibit drug-induced apoptosis, possibly through the NF-κB signaling pathway.

Keywords: breast cancer, TRIM32, NF-κB, apoptosis

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APA

Zhao, T.T., Jin, F., Li, J.G., Xu, Y.Y., Dong, H.T., Liu, Q., Xing, P., Zhu, G.L., Xu, H., Yin, S.C., Miao, Z.F. (2018). TRIM32 promotes proliferation and confers chemoresistance to breast cancer cells through activation of the NF-κB pathway. Journal of Cancer, 9(8), 1349-1356. https://doi.org/10.7150/jca.22390.

ACS

Zhao, T.T.; Jin, F.; Li, J.G.; Xu, Y.Y.; Dong, H.T.; Liu, Q.; Xing, P.; Zhu, G.L.; Xu, H.; Yin, S.C.; Miao, Z.F. TRIM32 promotes proliferation and confers chemoresistance to breast cancer cells through activation of the NF-κB pathway. J. Cancer 2018, 9 (8), 1349-1356. DOI: 10.7150/jca.22390.

NLM

CSE

Zhao TT, Jin F, Li JG, Xu YY, Dong HT, Liu Q, Xing P, Zhu GL, Xu H, Yin SC, Miao ZF. 2018. TRIM32 promotes proliferation and confers chemoresistance to breast cancer cells through activation of the NF-κB pathway. J Cancer. 9(8):1349-1356.

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