RETRACTED: lncRNA lnc-TSI Inhibits Metastasis of Clear Cell Renal Cell Carcinoma by Suppressing TGF-β-Induced Epithelial-Mesenchymal Transition (Retracted article. See vol. 29, pg. 550, 2022)

被引：16

作者：

Wang, Peng ^{[1
]}

Chen, Weixiong ^{[2
]}

Ma, Tongtong ^{[3
]}

Lin, Zhaoyu ^{[4
,5
]}

Liu, Chongbin ^{[1
]}

Liu, Youhua ^{[1
]}

Hou, Fan Fan ^{[1
,6
]}

机构：

[1] Southern Med Univ, Natl Clin Res Ctr Kidney Dis, State Key Lab Organ Failure Res, Div Nephrol,Nanfang Hosp, 1838 North Guangzhou Ave, Guangzhou 510515, Peoples R China

[2] Guangzhou Univ Tradit Chinese Med, Longgang Dist Cent Hosp, Dept Stomatol, Shenzhen 518116, Guangdong, Peoples R China

[3] Guangzhou Med Univ, Affiliated Hosp 1, Dept Anesthesiol, Guangzhou 510120, Peoples R China

[4] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510120, Peoples R China

[5] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Oral & Maxillofacial Surg, Guangzhou 510120, Peoples R China

[6] Guangzhou Regenerat Med & Hlth Guangdong Lab, Guangzhou 510005, Peoples R China

来源：

MOLECULAR THERAPY-NUCLEIC ACIDS | 2020年 / 22卷

基金：

中国国家自然科学基金; 中国博士后科学基金; 美国国家科学基金会;

关键词：

CANCER STATISTICS; MASTER REGULATOR; TARGETED THERAPY; FIBROSIS; SMAD3; EXPRESSION; NUCLEUS; GROWTH;

D O I：

10.1016/j.omtn.2020.08.003

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The transforming growth factor-beta (TGF-beta)/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-beta/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-beta/Smad3 pathway. Herein, we show that lnc-TSI was upregulated in ccRCC cells and tissue and was associated with activation of the TGF-beta/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-beta 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.

引用

页码：1 / 16

页数：16

共 33 条

[1] Transforming growth factor β as regulator of cancer stemness and metastasis [J].