Yanhua Wang1, Fang Jiang1, Yan Xiong1, Xiaoliang Cheng2, Zhimin Qiu3, Rongfeng Song4. 1. Department of Internal Medicine of Digestive Tumors, Jiangxi Provincial Cancer Hospital, China. 2. Department of Thoracic Surgery, Jiangxi Provincial Cancer Hospital, China. 3. Department of Comprehensive Oncology Medicine, Jiangxi Provincial Cancer Hospital, China. 4. Department of Internal Medicine of Digestive Tumors, Jiangxi Provincial Cancer Hospital, China. Electronic address: rongfengsong@126.com.
Abstract
AIMS: Long non-coding RNAs (lncRNAs) play key roles in regulating multiple cancers. TTN-AS1 was reported to function in several human malignancies. However, the biological function of TTN-AS1 in colorectal cancer (CRC) has not been explored. In this study, we aimed to investigate the role and the underlying mechanisms of TTN-AS1 in CRC progression. MAIN METHODS: RT-qPCR was used to detect the expression levels of TTN-AS1, miR-376a-3p and KLF15 in colorectal cancer tissues and cells. CCK-8, colony formation, flow cytometry and transwell assays were performed to determine the cell proliferation, apoptotic rate and invasion ability. Target genes were predicted using bioinformatics methods. si-RNA and miRNA inhibitor were transfected into CRC cells to explore the underlying mechanisms. Tumor xenografts were created to confirm the function of TTN-AS-1 in vivo. KEY FINDINGS: TTN-AS1 upregulation was observed both in CRC tissues and cell lines. Functional investigation showed that knockdown of TTN-AS1 inhibited CRC cell proliferation and invasion, while enhanced cell apoptosis. Bioinformatics analysis identified miR-376a-3p as a target of TTN-AS1. Transfection of miR-376a-3p inhibitor mitigated the alterations induced by TTN-AS1 knockdown. Moreover, TTN-AS1 positively regulated KLF15 via sponging miR-376a-3p. Additionally, these findings were supported by in vivo experiments. SIGNIFICANCE: In conclusions, TTN-AS1 promoted CRC proliferation and invasion through miR-376a-3p/KLF15 axis. Our findings suggested that TTN-AS1 might be a potential therapeutic target in CRC treatment.
AIMS: Long non-coding RNAs (lncRNAs) play key roles in regulating multiple cancers. TTN-AS1 was reported to function in several humanmalignancies. However, the biological function of TTN-AS1 in colorectal cancer (CRC) has not been explored. In this study, we aimed to investigate the role and the underlying mechanisms of TTN-AS1 in CRC progression. MAIN METHODS: RT-qPCR was used to detect the expression levels of TTN-AS1, miR-376a-3p and KLF15 in colorectal cancer tissues and cells. CCK-8, colony formation, flow cytometry and transwell assays were performed to determine the cell proliferation, apoptotic rate and invasion ability. Target genes were predicted using bioinformatics methods. si-RNA and miRNA inhibitor were transfected into CRC cells to explore the underlying mechanisms. Tumor xenografts were created to confirm the function of TTN-AS-1 in vivo. KEY FINDINGS:TTN-AS1 upregulation was observed both in CRC tissues and cell lines. Functional investigation showed that knockdown of TTN-AS1 inhibited CRC cell proliferation and invasion, while enhanced cell apoptosis. Bioinformatics analysis identified miR-376a-3p as a target of TTN-AS1. Transfection of miR-376a-3p inhibitor mitigated the alterations induced by TTN-AS1 knockdown. Moreover, TTN-AS1 positively regulated KLF15 via sponging miR-376a-3p. Additionally, these findings were supported by in vivo experiments. SIGNIFICANCE: In conclusions, TTN-AS1 promoted CRC proliferation and invasion through miR-376a-3p/KLF15 axis. Our findings suggested that TTN-AS1 might be a potential therapeutic target in CRC treatment.