Open AccessThe oncogenic role of MUC12 in RCC progression depends on c‐Jun/TGF‐β signalling
Author(s) -
Gao ShengLin,
Yin Rui,
Zhang LiFeng,
Wang SiMin,
Chen JiaSheng,
Wu XingYu,
Yue Chuang,
Zuo Li,
Tang Min
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15515
Subject(s) - cancer research , transactivation , renal cell carcinoma , gene knockdown , cell growth , transforming growth factor , tumor progression , biology , targeted therapy , cell , cancer , transcription factor , medicine , cell culture , gene , biochemistry , genetics
Renal cell carcinoma (RCC) is a common kidney cancer worldwide. Even though current treatments show promising therapeutic effectiveness, metastatic RCC still has limited therapeutic options so that novel treatments were urgently needed. Here, we identified that MUC12 was overexpressed in RCC patients and served as poor prognostic factor for RCC progression. Overexpression of MUC12 increased RCC cell growth and cell invasion while deficiency of MUC12 exerted opposite effects on RCC cells. Mechanistic dissection demonstrated that MUC12‐mediated RCC cell growth and cell invasion were dependent of TGF‐β1 signalling because they could be blocked in the presence of TGF‐β1 inhibitor. Moreover, the regulation of TGF‐β1 by MUC12 relied on the transactivation of c‐Jun. MUC12 promoted the recruitment of c‐Jun on the promoter of TGF‐β1, leading to its transcription. Importantly, knockdown of c‐Jun also attenuated MUC12‐mediated TGF‐β1 induction and RCC cell invasion. In summary, our study defines the role of MUC12 in RCC progression and provides rational to develop novel targeted therapy to battle against RCC.