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Jin Xun, Chunfeng Wang, Jianning Yao, Bing Gao, Lianfeng Zhang Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, People’s Republic of ChinaCorrespondence: Lianfeng ZhangDepartment of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshedong Road, Erqi District, Zhengzhou City 450052, Henan Province, People’s Republic of ChinaTel/Fax +86-371-66862062Email xiaobanli1027@126.comPurpose: Long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) has been reported to dysregulate in many tumors. However, the mechanism of HOTAIR was rarely reported in GC.Methods: The levels of HOTAIR, microRNA-618 (miR-618) and Krueppel-like factor 12 (KLF12) in GC tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The cell viability and apoptotic rate were assessed via cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The migrating and invading abilities were tested by Transwell assay. The protein levels of KLF12, p-PI3K, PI3K, p-ATK and ATK were measured by Western blot assay. These interactions between miR-618 and HOTAIR or KLF12 were predicted by DIANA tools, and then, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to validate these interactions. Besides, the xenograft tumor experiment was performed to further verify the roles of HOTAIR in GC.Results: The levels of HOTAIR and KLF12 were significantly upregulated and the level of miR-618 was strikingly downregulated in GC tissues and cells. miR-618 was verified as a direct target of HOTAIR or KLF12. HOTAIR silencing blocked GC progression and PI3K/ATK signaling pathway by sponging miR-618 and also restrained xenograft tumor growth in vivo. miR-618 inhibited GC progression and PI3K/ATK signaling pathway by targeting KLF12. Mechanistically, HOTAIR modulated KLF12 expression by sponging miR-618 in GC cells.Conclusion: These data unraveled that HOTAIR promoted GC progression through PI3K/ATK signaling pathway via miR-618/KLF12 axis.Keywords: HOTAIR, miR-618, KLF12, PI3K/ATK signaling pathway, gastric cancer |
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