Long Non-Coding RNA TTN-AS1 Promotes the Proliferation and Invasion of | OTT – Dove Medical Press

Zhenhua Cui,1 Bingbing Han,2 Xianren Wang,1 Zhiwen Li,1 Jianxin Wang,1 Yanfeng Lv1

1Department of Colorectal & Anal Surgery, The Second Hospital of Shandong University, Jinan 250033, Peoples Republic of China; 2Microcirculation Laboratory, Shandong University of Traditional Chinese Medicine, Jinan, 250014, Peoples Republic of China

Correspondence: Yanfeng LvDepartment of Colorectal & Anal Surgery, The Second Hospital of Shandong University, No. 247 BeiYuan Street, Jinan 250033, Peoples Republic of ChinaEmail ttdpilsxpsle11@163.com

Introduction: Long non-coding RNAs (lncRNAs) have obtained increasing attention due to their regulatory functions in many cancers. This work aimed to investigate the functional roles of lncRNA TTN-AS1 in colorectal cancer (CRC) and to explore the underlying mechanisms.Methods: The expression profiles of TTN-AS1 and miR-497 in CRC tissues and cell lines were determined by RT-qPCR analysis. MTT assay, transwell assay, western blot analysis, and xenograft tumors in nude mice were employed to analyze the effects of TTN-AS1 on the proliferation, migration, invasion, EMT, and in vivo tumorigenesis of CRC cells. Bioinformatics analysis and dual-luciferase reporter assay determined the direct binding relation betweenTTN-AS1 and miR-497 in CRC.Results: We observed a significant increase of TTN-AS1 expression level in CRC tissues and cell lines compared with normal counterparts. High expression of TTN-AS1 predicted a poor prognosis and was correlated with aggressive clinicopathological characteristics in CRC patients. Functionally, gain- and loss-of-function studies indicated that TTN-AS1 knockdown suppressed the proliferation, migration, invasion and epithelialmesenchymal transition of CRC cells in vitro, whereas TTN-AS1 overexpression showed the complete opposite effects. Mechanistically, we found that TTN-AS1 could directly interact with miR-497, and co-transfection with miR-497 mimics blocked the activation of PI3K/Akt/mTOR signaling, and reversed the effects of TTN-AS1 overexpression in CRC cells.Conclusion: To conclude, our findings provide novel insight into CRC tumorigenesis and indicate that TTN-AS1 may serve as a potential therapeutic target for CRC treatment.

Keywords: colorectal cancer, long non-coding RNA TTN-AS1, epithelial-mesenchymal transition, microRNA-497, PI3K/Akt/mTOR signaling

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Long Non-Coding RNA TTN-AS1 Promotes the Proliferation and Invasion of | OTT - Dove Medical Press