Lei Tian1, Zhi-Feng Zhao2, Ling Xie3, Jin-Peng Zhu4. 1. Department of Gastroenterol, Jinzhou Medical University, Affilliated Hospital 1, Jinzhou, 121000, Liaoning Province, People's Republic of China. Electronic address: yleitianxq@sina.com. 2. Department of Gastroenterol, the Fourth Affiliated Hospital of China Medical University, Shenyang, 110000, Liaoning Province, People's Republic of China. 3. Department of Anatomy, Jinzhou Medical University, Jinzhou, 121000, Liaoning Province, People's Republic of China. 4. Department of Gastroenterol, Jinzhou Medical University, Affilliated Hospital 1, Jinzhou, 121000, Liaoning Province, People's Republic of China.
Abstract
AIMS: The purpose of this study was to investigate the role of long non-coding RNA taurine-upregulated gene 1 (TUG1) in colon cancer (Cc) and related molecular mechanisms. MATERIALS AND METHODS: RT-qPCR, Western blot and immunohistochemistry were used to detect the expression of related proteins. BrdU and Transwell assays were used to detect cell proliferation and invasion, respectively. Immunofluorescence was used to detect the expression of Vimentin. KEY FINDINGS: TUG1 expression was up-regulated in CaCO-2, SW620 and HT-29 cells, while miR-26a-5p was down-regulated. Bioinformatics analysis showed that miR-26a-5p was the target of TUG1, and the targeting relationship was further confirmed by dual-luciferase report analysis. Besides, matrix metalloproteinases-14 (MMP-14) was a target of mir-26a-5p. Knockdown of TUG1 by shRNA (sh-TUG1) inhibited MMP-14 expression. Functional analysis showed that sh-TUG1 significantly inhibited Cc cell proliferation, invasion and epithelial-mesenchymal transformation (EMT). Notably, miR-26a-5p inhibitor reversed the promotion of Cc caused by sh-TUG1. Mechanically, the overexpression of TUG1 significantly up-regulated the levels of MMP-14, VEGF, p-p38 mitogen-activated protein kinase (p-p38 MAPK) and p-HSP27 (heat shock protein 27), and promoted the proliferation, invasion and EMT of Cc cells. However, MAPK pathway inhibitor SB203580 has shown the opposite effect. Additionally, animal studies have shown that sh-TUG1 inhibited tumor growth and motility in vivo in the same way. SIGNIFICANCE: This study demonstrated that TUG1 accelerates the development of colon cancer by regulating miR-26a-5p/MMP14/p38 MAPK/Hsp27 axis in vitro and in vivo. Therefore, TUG1 provides a new direction for the treatment of Cc.
AIMS: The purpose of this study was to investigate the role of long non-coding RNA taurine-upregulated gene 1 (TUG1) in colon cancer (Cc) and related molecular mechanisms. MATERIALS AND METHODS: RT-qPCR, Western blot and immunohistochemistry were used to detect the expression of related proteins. BrdU and Transwell assays were used to detect cell proliferation and invasion, respectively. Immunofluorescence was used to detect the expression of Vimentin. KEY FINDINGS:TUG1 expression was up-regulated in CaCO-2, SW620 and HT-29 cells, while miR-26a-5p was down-regulated. Bioinformatics analysis showed that miR-26a-5p was the target of TUG1, and the targeting relationship was further confirmed by dual-luciferase report analysis. Besides, matrix metalloproteinases-14 (MMP-14) was a target of mir-26a-5p. Knockdown of TUG1 by shRNA (sh-TUG1) inhibited MMP-14 expression. Functional analysis showed that sh-TUG1 significantly inhibited Cc cell proliferation, invasion and epithelial-mesenchymal transformation (EMT). Notably, miR-26a-5p inhibitor reversed the promotion of Cc caused by sh-TUG1. Mechanically, the overexpression of TUG1 significantly up-regulated the levels of MMP-14, VEGF, p-p38 mitogen-activated protein kinase (p-p38 MAPK) and p-HSP27 (heat shock protein 27), and promoted the proliferation, invasion and EMT of Cc cells. However, MAPK pathway inhibitor SB203580 has shown the opposite effect. Additionally, animal studies have shown that sh-TUG1 inhibited tumor growth and motility in vivo in the same way. SIGNIFICANCE: This study demonstrated that TUG1 accelerates the development of colon cancer by regulating miR-26a-5p/MMP14/p38 MAPK/Hsp27 axis in vitro and in vivo. Therefore, TUG1 provides a new direction for the treatment of Cc.