Breast cancer (BC) is the most prevalent tumour in women worldwide. USP30 is a deubiquitinase that has been previously reported to promote tumour progression and lipid synthesis in hepatocellular carcinoma. However, the role of USP30 in breast cancer remains unclear. Therefore, we investigated its biological action and corresponding mechanisms in vitro and in vivo. In our study, we found that USP30 was highly expressed in breast cancer samples and correlated with a poor patient prognosis. Knockdown of USP30 significantly suppressed the proliferation, invasion and migration abilities of BC cells in vitro and tumour growth in vivo, whereas overexpression of USP30 exhibited the opposite effect. Mechanistically, we verified that USP30 interacts with and stabilises Snail to promote its protein expression through deubiquitination by K48-linked polyubiquitin chains and then accelerates the EMT program. More importantly, USP30 reduced the chemosensitivity of BC cells to paclitaxel (PTX). Collectively, these data demonstrate that USP30 promotes the BC cell EMT program by stabilising Snail and attenuating chemosensitivity to PTX and may be a potential therapeutic target in BC.

乳腺癌（BC）是全世界女性中最常见的肿瘤。USP30 是一种去泛素酶，此前已报道可促进肝细胞癌的肿瘤进展和脂质合成。然而，USP30 在乳腺癌中的作用仍不清楚。因此，我们在体外和体内研究了其生物学作用和相应的机制。在我们的研究中，我们发现 USP30 在乳腺癌样本中高表达，并且与患者预后不良相关。USP30的敲低显着抑制BC细胞的体外增殖、侵袭和迁移能力以及体内肿瘤的生长，而USP30的过表达则表现出相反的效果。从机制上，我们验证了USP30与Snail相互作用并稳定Snail，通过K48连接的多聚泛素链去泛素化促进其蛋白表达，然后加速EMT程序。更重要的是，USP30降低了BC细胞对紫杉醇（PTX）的化疗敏感性。总的来说，这些数据表明 USP30 通过稳定 Snail 并减弱对 PTX 的化学敏感性来促进 BC 细胞 EMT 程序，并且可能是 BC 的潜在治疗靶点。