Open AccessSMAD3/SP1 complex‐mediated constitutive active loop between lncRNA PCAT7 and TGF‐β signaling promotes prostate cancer bone metastasis
Author(s) -
Lang Chuandong,
Dai Yuhu,
Wu Zhengquan,
Yang Qing,
He Shaofu,
Zhang Xin,
Guo Wei,
Lai Yingrong,
Du Hong,
Wang Hehe,
Ren Dong,
Peng Xinsheng
Publication year - 2020
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12634
Subject(s) - bone metastasis , metastasis , prostate cancer , cancer research , gene knockdown , smad , downregulation and upregulation , signal transduction , transforming growth factor , biology , cancer , medicine , microbiology and biotechnology , cell culture , gene , biochemistry , genetics
Bone metastasis is associated with cancer‐related death in patients with prostate cancer (PCa). Long noncoding RNAs (lncRNAs) play critical roles in tumor progression of PCa. Nevertheless, the biological function of lncRNAs in PCa bone metastasis remains unclear. PCAT7 was identified as a bone metastasis‐related lncRNA via analyzing TCGA dataset. Meanwhile, PCAT7 was found to be elevated in primary PCa tissues with bone metastasis and associated with bone metastasis status and poor prognosis of patients with PCa. Functionally, our results reveal that PCAT7 overexpression promotes PCa bone metastasis in vivo , as well as migration, invasion, and EMT of PCa cells in vitro ; on the contrary, PCAT7 knockdown has an inverse effect. Mechanistically, PCAT7 activates TGF‐β/SMAD signaling by upregulating TGFBR1 expression via sponging miR‐324‐5p. In turn, TGF‐β signaling forms a positive feedback loop with PCAT7 via SMAD3/SP1 complex‐induced PCAT7 upregulation. Finally, the clinical positive correlation between PCAT7 and TGFBR1 and TGF‐β signaling activity, and the negative association with miR‐324‐5p are further demonstrated in PCa tissues and clinical primary PCa cells. This study reveals a novel mechanism that is responsible for the constitutive activation of TGF‐β signaling in PCa bone metastasis, implying that PCAT7 can act as a potential therapeutic target against bone metastasis of PCa via disrupting the constitutive active loop between PCAT7 and TGF‐β signaling.