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lncRNA lnc-TSI Inhibits Metastasis of Clear Cell Renal Cell Carcinoma by Suppressing TGF-β-Induced Epithelial-Mesenchymal Transition.

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机构: [1]Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou 510515, China [2]Department of Stomatology, Longgang District Central Hospital, Affiliated to Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong 518116, China [3]Department of Anesthesiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China [4]Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China [5]Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China [6]Guangzhou Regenerative Medicine and Health Guangdong Laboratory, 510005 Guangzhou, China
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关键词: clear cell renal cell carcinoma long noncoding RNA metastasis TGF-β signaling

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The transforming growth factor-β (TGF-β)/Smads signal plays an important role in cancer metastasis by mediating the epithelial-mesenchymal transition (EMT) in cancer cells. lnc-TSI is a recently identified long noncoding RNA that negatively regulates the TGF-β/Smads signal. The present study was conducted to test the hypothesis that lnc-TSI inhibits metastasis in clear cell renal cell carcinoma (ccRCC) by regulating the TGF-β/Smad3 pathway. Herein, we show that lnc-TSI was upregulated in ccRCC cells and tissue and was associated with activation of the TGF-β/Smads signal. Depleting lnc-TSI enhanced tumor cell invasion and metastasis in vitro and ccRCC lung metastasis in vivo, whereas overexpressing lnc-TSI inhibited ccRCC cell invasion and tumor metastasis. Mechanistic studies indicated that lnc-TSI specifically inhibited the phosphorylation of Smad3 and subsequent EMT by binding with the MH2 domain of Smad3 to block the interaction between Smad3 and TGF-β receptor I in ccRCC cells. In a cohort of 150 patients with ccRCC, expression of lnc-TSI in tumors was negatively correlated with phosphorylated (p)Smad3 and activated EMT markers. Patients with expression of tumor lnc-TSI greater than or equal to the median at radical nephrectomy had a higher survival rate compared to those with lnc-TSI below the median during follow-up. These findings reveal a new regulatory mechanism of ccRCC metastasis and suggest a potential molecular target for the development of anti-cancer drugs. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

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出版当年[2019]版:
大类 | 2 区 医学
小类 | 2 区 医学:研究与实验
最新[2025]版:
大类 | 2 区 医学
小类 | 2 区 医学:研究与实验
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出版当年[2018]版:
Q1 MEDICINE, RESEARCH & EXPERIMENTAL
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Q1 MEDICINE, RESEARCH & EXPERIMENTAL

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第一作者机构: [1]Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou 510515, China
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通讯机构: [1]Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou 510515, China [6]Guangzhou Regenerative Medicine and Health Guangdong Laboratory, 510005 Guangzhou, China [*1]Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, 1838 North Guangzhou Avenue, Guangzhou 510515, China.
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