Xue-Ting Ye1, Hang Huang2, Wei-Ping Huang2, Wei-Lie Hu3. 1. Graduate School, Southern Medical University, Guangzhou, China; Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 2. Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 3. Graduate School, Southern Medical University, Guangzhou, China; Department of Urology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China. Electronic address: profhu_weilie@163.com.
Abstract
BACKGROUND: Recent studies have characterized a novel but extremely conserved long non-coding RNA (LncRNA) THOR. THOR directly associates with insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to promote mRNA stabilization of key pro-cancerous genes. RESULTS: Here, we show that THOR is expressed in human renal cell carcinoma (RCC) tissues and established/primary human RCC cells. It was not detected in normal renal tissues nor in HK-2 and primary human renal epithelial cells. THOR silencing (by targeted siRNAs) or CRISPR/Cas9 knockout inhibited RCC cell growth, viability and proliferation in vitro. Reversely, forced over-expression of THOR promoted RCC cell survival and proliferation. IGF2BP1-regulated genes, including IGF2, GLI1 and Myc, were downregulated by THOR silencing or knockout, but they were upregulated after THOR over-expression. In vivo, THOR-knockout 786-O tumors grew significantly slower than the control tumors in nude mice. CONCLUSION: THOR expression promotes RCC cell growth in vitro and in vivo. THOR could be a novel and important therapeutic target for human RCC.
BACKGROUND: Recent studies have characterized a novel but extremely conserved long non-coding RNA (LncRNA) THOR. THOR directly associates with insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to promote mRNA stabilization of key pro-cancerous genes. RESULTS: Here, we show that THOR is expressed in humanrenal cell carcinoma (RCC) tissues and established/primary humanRCC cells. It was not detected in normal renal tissues nor in HK-2 and primary human renal epithelial cells. THOR silencing (by targeted siRNAs) or CRISPR/Cas9 knockout inhibited RCC cell growth, viability and proliferation in vitro. Reversely, forced over-expression of THOR promoted RCC cell survival and proliferation. IGF2BP1-regulated genes, including IGF2, GLI1 and Myc, were downregulated by THOR silencing or knockout, but they were upregulated after THOR over-expression. In vivo, THOR-knockout 786-O tumors grew significantly slower than the control tumors in nude mice. CONCLUSION:THOR expression promotes RCC cell growth in vitro and in vivo. THOR could be a novel and important therapeutic target for humanRCC.
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