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SMAD3/SP1 complex‐mediated constitutive active loop between lncRNA PCAT7 and TGF‐β signaling promotes prostate cancer bone metastasis
by
Lang, Chuandong
, Zhang, Xin
, Wang, Hehe
, Guo, Wei
, Du, Hong
, Wu, Zhengquan
, Dai, Yuhu
, Peng, Xinsheng
, Lai, Yingrong
, Ren, Dong
, Yang, Qing
, He, Shaofu
in
Animals
/ Bone cancer
/ bone metastasis
/ Bone Neoplasms - genetics
/ Bone Neoplasms - pathology
/ Bone Neoplasms - secondary
/ Breast cancer
/ Cell Line, Tumor
/ Epithelial-Mesenchymal Transition
/ Gene Expression Regulation, Neoplastic
/ Humans
/ Immunoglobulins
/ lncRNA PCAT7
/ Male
/ Metastases
/ Metastasis
/ Mice
/ MicroRNAs
/ miR‐324‐5p
/ Neoplasm Invasiveness - genetics
/ Neoplasm Invasiveness - pathology
/ Plasmids
/ Prostate cancer
/ Prostatic Neoplasms - genetics
/ Prostatic Neoplasms - pathology
/ RNA, Long Noncoding - genetics
/ Signal Transduction
/ Smad protein
/ Smad3 protein
/ Smad3 Protein - metabolism
/ Sp1 Transcription Factor - metabolism
/ TGF‐β signaling
/ Therapeutic applications
/ Transforming Growth Factor beta - metabolism
/ Transforming growth factor-b
2020
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SMAD3/SP1 complex‐mediated constitutive active loop between lncRNA PCAT7 and TGF‐β signaling promotes prostate cancer bone metastasis
by
Lang, Chuandong
, Zhang, Xin
, Wang, Hehe
, Guo, Wei
, Du, Hong
, Wu, Zhengquan
, Dai, Yuhu
, Peng, Xinsheng
, Lai, Yingrong
, Ren, Dong
, Yang, Qing
, He, Shaofu
in
Animals
/ Bone cancer
/ bone metastasis
/ Bone Neoplasms - genetics
/ Bone Neoplasms - pathology
/ Bone Neoplasms - secondary
/ Breast cancer
/ Cell Line, Tumor
/ Epithelial-Mesenchymal Transition
/ Gene Expression Regulation, Neoplastic
/ Humans
/ Immunoglobulins
/ lncRNA PCAT7
/ Male
/ Metastases
/ Metastasis
/ Mice
/ MicroRNAs
/ miR‐324‐5p
/ Neoplasm Invasiveness - genetics
/ Neoplasm Invasiveness - pathology
/ Plasmids
/ Prostate cancer
/ Prostatic Neoplasms - genetics
/ Prostatic Neoplasms - pathology
/ RNA, Long Noncoding - genetics
/ Signal Transduction
/ Smad protein
/ Smad3 protein
/ Smad3 Protein - metabolism
/ Sp1 Transcription Factor - metabolism
/ TGF‐β signaling
/ Therapeutic applications
/ Transforming Growth Factor beta - metabolism
/ Transforming growth factor-b
2020
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SMAD3/SP1 complex‐mediated constitutive active loop between lncRNA PCAT7 and TGF‐β signaling promotes prostate cancer bone metastasis
by
Lang, Chuandong
, Zhang, Xin
, Wang, Hehe
, Guo, Wei
, Du, Hong
, Wu, Zhengquan
, Dai, Yuhu
, Peng, Xinsheng
, Lai, Yingrong
, Ren, Dong
, Yang, Qing
, He, Shaofu
in
Animals
/ Bone cancer
/ bone metastasis
/ Bone Neoplasms - genetics
/ Bone Neoplasms - pathology
/ Bone Neoplasms - secondary
/ Breast cancer
/ Cell Line, Tumor
/ Epithelial-Mesenchymal Transition
/ Gene Expression Regulation, Neoplastic
/ Humans
/ Immunoglobulins
/ lncRNA PCAT7
/ Male
/ Metastases
/ Metastasis
/ Mice
/ MicroRNAs
/ miR‐324‐5p
/ Neoplasm Invasiveness - genetics
/ Neoplasm Invasiveness - pathology
/ Plasmids
/ Prostate cancer
/ Prostatic Neoplasms - genetics
/ Prostatic Neoplasms - pathology
/ RNA, Long Noncoding - genetics
/ Signal Transduction
/ Smad protein
/ Smad3 protein
/ Smad3 Protein - metabolism
/ Sp1 Transcription Factor - metabolism
/ TGF‐β signaling
/ Therapeutic applications
/ Transforming Growth Factor beta - metabolism
/ Transforming growth factor-b
2020
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SMAD3/SP1 complex‐mediated constitutive active loop between lncRNA PCAT7 and TGF‐β signaling promotes prostate cancer bone metastasis
Journal Article
SMAD3/SP1 complex‐mediated constitutive active loop between lncRNA PCAT7 and TGF‐β signaling promotes prostate cancer bone metastasis
2020
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Overview
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.
lncRNA PCAT7 is upregulated in primary prostate cancer tissues with bone metastasis. 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. This feedback loop promotes prostate cancer bone metastasis.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
Subject
/ Epithelial-Mesenchymal Transition
/ Gene Expression Regulation, Neoplastic
/ Humans
/ Male
/ Mice
/ Neoplasm Invasiveness - genetics
/ Neoplasm Invasiveness - pathology
/ Plasmids
/ Prostatic Neoplasms - genetics
/ Prostatic Neoplasms - pathology
/ RNA, Long Noncoding - genetics
/ Sp1 Transcription Factor - metabolism
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