TRIM3 inhibits P53 signaling in breast cancer cells

Abstract

BackgroundBeast cancer is the most common women cancer worldwide, while two third of them are ER alpha positive breast cancer. Among the ER alpha positive breast cancer, about 80% are P53 wild type, indicating the potential tumor suppression role in ER alpha positive breast cancer. Since P53 is an important safeguard to inhibit cell malignant transformation, reactivating P53 signaling could a plausible approach to treat breast cancer.MethodsTRIM3 protein levels were measured by western blot, while the P53 classical target genes were measured by real-time PCR. WST1 assay were used to measure cell proliferation, while cleaved caspase-3 was used to detect cell apoptosis. Protein stability and ubiquitin assay were used to detect the P53 protein ubiquitin and stability. The immuno-precipitation assays were used to detect the protein interactions. Immuno-staining was used to detect the protein localization of P53 and TRIM3, while the ubiquitin-based immuno-precipitation assays were used to detect the specific ubiquitination manner of P53.ResultsIn our study, we identified TRIM3 as an endogenous inhibitor for P53 signaling. TRIM3 depletion inhibited breast cancer cell proliferation and promoted apoptosis. In addition, TRIM3 depletion increased P53 protein level in breast cancer cell. Further investigation showed that TRIM3 could associate with P53 and promote P53 K48-linked ubiquitination and degradation.ConclusionOur study identified a novel post-translational modification mechanism between TRIM3 and P53. TRIM3 depletion or blockage could be a promising strategy to rescue P53 signaling and inhibit breast cancer progression.Highlights1. TRIM3 facilitates breast cancer cell growth and anti-apotosis.2. TRIM3 inhibits P53 protein and its signaling activity.3. TRIM3 interacts with P53 and promotes P53 K48-linked ubiquitination and degradation.

TRIM3 and TRIM16 as potential tumor suppressors in breast cancer patients

“…Huang et al and Song et al suggested that TRIM3 is a tumor suppressor in the liver and cervical cancers, respectively [14,15]. However, Wang et al reported that TRIM3 plays a stimulating role in the MCF7 breast cancer cell line [16]. On the other hand, the study conducted by Marshall et al suggests that TRIM16 acts as a tumor suppressor in neuroblastoma cells [17].…”

“…Yongzhen Li reports in his study that the oncogenic miR-4513 plays its role in MCF-7 cell line through inhibition of TRIM3, which leads to increased cell migration, invasion, colony formation and proliferation [19]. However, the study of Wang introduces the TRIM3 as an oncogenic factor in breast cancer, which promotes the proliferation of breast cancer cells through suppression of P53 signaling [20]. TRIM16 is suggested by Kim as a suppressor factor in breast cancer that reduces the viability of breast cancer cells [21].…”

Knockdown of Brachyury Suppresses Breast Cancer Cell Proliferation and Migration via Targeting E2F3

“…Breast cancer is a heterogeneous disease. According to the expression of progesterone receptor (PR), estrogen receptor (ER), ERBB2 receptor (HER2), and Ki-67, breast cancer can be divided into fve groups: triple negative, HER2-enriched (non-luminal), Luminal B-like HER2+, Luminal A type, Luminal B type [3,4]. Clinically, adjuvant therapy using endocrine therapy and surgical treatment has markedly reduced Luminal A primary breast tumors death.…”

TRIM3 And TRIM16 As Tumor Suppressors In Breast Cancer Patients

“…Huang et al (2017) and Song et al (2018) suggested that TRIM3 is a tumor suppressor in the liver and cervical cancers, respectively [14,15]. However, Wang et al (2020) reported that TRIM3 plays a stimulating role in the MCF7 breast cancer cell line [16]. On the other hand, the study conducted by Marshall et al (2010) suggests that TRIM16 acts as a tumor suppressor in neuroblastoma cells [17].…”