Background and objectives

Breast cancer is one of the leading causes of mortality among women worldwide.

Tumour necrosis factor α-induced protein 3-interacting protein 1 (TNIP1) is a ubiquitin-binding protein that is widely expressed, but its function in breast cancer cells remains unknown.

This study aimed to elucidate the molecular mechanism of TNIP1 regulation in the proliferation and apoptosis of breast cancer cells.

Methods

A colony formation assay was conducted on MCF-7 and T47D cells stably transfected with TNIP1/cyclin G1 (CCNG1) short hairpin RNAs.

Quantitative polymerase chain reaction was performed to assess the relative abundances of TNIP1, CCNG1, and cyclin D1 (CCND1) messenger RNAs.

Immunoprecipitation and immunoblotting were used to detect the expression of TNIP1, CCNG1, CCND1, and related proteins.

A dual-luciferase reporter assay was employed to explore the molecular mechanism of TNIP1 in signal transduction.

Caspase activity in MCF-7 and T47D cells transfected with TNIP1 short hairpin RNAs was measured using the Caspase-Glo 3/7 assay.

Results

Ablation of TNIP1 induced growth arrest in breast cancer cells.

TNIP1 directly interacted with CCNG1, and TNIP1 knockdown increased the ubiquitination of CCNG1.

CCNG1 knockdown also induced growth arrest in MCF-7 and T47D cells.

Furthermore, TNIP1 knockdown activated the NF-κB pathway and induced apoptosis in these cells.

Conclusions

We demonstrate that TNIP1 knockdown leads to growth arrest in breast cancer cells through interacting with CCNG1 and promoting its ubiquitination.

This mechanism reveals a novel pathway by which TNIP1 regulates cell proliferation in breast cancer.

Our findings also reveal that TNIP1 knockdown not only affects CCNG1 levels but also activates the NF-κB signalling pathway, leading to increased apoptosis in MCF-7 cells.

Overall, our study highlights TNIP1 as a crucial marker and suggests its potential as a target for breast cancer therapies.

The study was recently published in the Oncology Advances.

Source: Xia & He Publishing Inc.