The Potential Role of Ubiquitin-Conjugating Enzyme E2C (UBE2C) in Breast Cancer Progression by Regulating the JNK Signaling Pathway.

Abstract

Background: We explored the relation and critical roles of ubiquitin-conjugating enzyme E2C (UBE2C) in breast cancer (BC).

Methods: The UBE2C expression levels and relation with clinical features and prognosis in BC patients were examined using online data. UBE2C expression in BC cell lines was assessed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot. To assess cell proliferation, migration, invasion, and apoptosis, tests were conducted using CCK-8, colony formation assay, wound healing assay, transwell assay, and flow cytometry. Subcutaneous tumor model was used to evaluate the effects of UBE2C on tumor growth in mice. The effects of UBE2C on tumor formation in mice were assessed by subcutaneous tumor model, and UBE2C, E-cadherin, Ki-67, and p53 were detected by an immunohistochemistry assay. Finally, the connection of UBE2C with Epithelial-mesenchymal transition markers and proteins of proliferation, apoptosis, JNK pathway were tested by western blot.

Results: UBE2C was upregulated in BC tissues in TCGA and Gene expression omnibus (GEO) datasets, and high levels UBE2C was correlated with the advanced stage cases, some molecular types and poor prognosis in BC patients. In vitro, UBE2C was also overexpressed in BC cell lines, and suppressed apoptosis and encouraged cell growth, migration, invasion, and metastasis. Moreover, UBE2C knockdown suppressed the growth of transplanted tumor in mice.

Conclusions: These results suggested that UBE2C facilitated the process of proliferation, metastasis through the modulation of the JNK signaling pathway, highlighting a previously underexplored mechanistic axis and predicting the potentiality of UBE2C as a therapeutic target for BC patients.