Table 1.
Summary of UBE2C’s role and impact in different types of malignancies.
| Malignancy Type | Synthesized Outcomes | References |
|---|---|---|
| Breast cancer |
UBE2C overexpression is closely associated with high histological grade, lymphovascular invasion, larger tumors, HER2 positivity, early metastasis, increased mortality rates, and worse prognosis. Higher UBE2C levels are positively correlated with N-cadherin, matrix metalloproteinases, and cell cycle-related biomarkers (such as p53, Ki67, PI3K, and EGFR) while being negatively related to E-cadherin. ALKBH5 promotes breast cancer cell growth, stemness, and metastasis through the UBE2C/p53 axis. UBE2C knockdown increases PTEN levels and decreases p-AKT, p-mTOR, and HIF-1α levels, declining proliferation and invasion ability through the impairment of the AKT/mTOR signaling pathway. UBE2C knockdown sensitizes breast cancer cells to radiation and chemotherapy. UBE2C is correlated with CTLA4 expression. |
[55,56,57,58,59,60,61] |
| Lung cancer | High UBE2C expression is associated with high histological grade, sex, TNM stage, age, angiogenesis, post-operative survival time, and poor prognosis in NSLCL. UBE2C knockdown inhibited NSLCL cell proliferation and increased chemotherapeutical sensitivity. UBE2C overexpression may play an important role in lung cancer EMT, invasion, migration, and metastasis. UBE2C expression is correlated with the p53 and EGFR mutational status. The UBE2C/CDH1/DEPTOR axis regulates cell cycle progression and autophagy in NSCLC. |
[62,63,64,65,66,67] |
| Hepatocellular carcinoma |
UBE2C overexpression is associated with high histological grade, p53 mutation, and poor survival. UBE2C expression is increased in sorafenib-resistant HepG2 cells. UBE2C silencing represses proliferation and colony formation of MHCC97H cells and overexpression enhances aggressiveness. UBE2C levels are positively associated with regulatory T cells and TFH infiltration and negatively correlated with infiltration of monocytes. UBE2C depletion sensitizes cells to chemotherapeutical drugs. |
[68,69,70] |
| Endometrial carcinoma |
UBE2C is upregulated in endometrial cancer cell lines and patients and is associated with high histological grade, worse subtypes, frequent recurrence, shorter overall survival, and poor outcome. UBE2C knockdown upregulates E-cadherin and downregulates vimentin, leading to a reduction in proliferation, invasion, and migration in RL95-2 and Ishikawa cells. UBE2C promotes EMT by negative p53 modulation. |
[71] |
| Thyroid carcinoma | UBE2C is strongly associated with immune response. UBE2C knockdown decreases cell proliferation, migration, and invasion, promotes apoptosis, and reduces chemotherapeutic resistance. |
[72] |
| Adrenocortical/ clear cell renal carcinoma | UBE2C expression is correlated with advanced tumor stage, high histological grade, and poor prognosis in renal carcinoma. UBE2C overexpression induces m6A methylation and promotes self-renewal of stem cells in adrenocortical carcinoma. UBE2C knockdown reduces proliferation, invasion, and migration, diminishes DNA damage repair, and induces apoptosis through cell cycle and EMT inhibition in adrenocortical carcinoma. UBE2C is strongly correlated with stromal score, immune score, and infiltration of M0 macrophages, regulatory T cells, and CD4+ memory T cells in clear cell renal carcinoma. |
[73,74] |
| Brain tumors | UBE2C overexpression is associated with high histological grade, decreased overall survival, and poor prognosis in glioma. UBE2C expression is related to FoxM1 and AURKB levels. FoxM1 binds to the UBE2C promoter, inducing its transcription. UBE2C silencing induces autophagy, inhibits cell viability, promotes cell apoptosis, and promotes the activation of p53 in glioma cells. UBE2C knockdown inhibits the Akt-mTOR signaling pathway in glioma cells. Enriched UBE2C expression is associated with resistance to temozolomide and radiotherapy in glioma. UBE2C is highly expressed in brain metastasis from different origins and is associated with declined survival and leptomeningeal dissemination. Dactolisib (PI3K/mTOR inhibitor) treats UBE2C-driven breast and lung cancer brain metastasis, and early treatment prevents leptomeningeal dissemination in vivo. |
[75,76,77,78] |
Abbreviations. UBE2C: ubiquitin-conjugating enzyme, HER2: human epidermal growth factor receptor 2, p53: tumor suppressor p53, Ki67: marker of proliferation Ki-67, PI3K: phosphoinositide 3-kinase, EGFR: epidermal growth factor receptor, HIF-1α: hypoxia-inducible factor 1-alpha, NSCLC: non-small cell lung carcinomas, TNM: TNM Classification of Malignant Tumors, AKT: AKT serine/threonine kinase, CTLA4: cytotoxic T-lymphocyte-associated protein 4, EMT: epithelial–mesenchymal transition, TFH: T follicular helper cells, FoxM1: Forkhead box M1, AURKB: aurora kinase B, mTOR: mammalian target of rapamycin.