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27 February 2019 : Laboratory Research  

Long Chain Non-Coding RNA (lncRNA) HOTAIR Knockdown Increases miR-454-3p to Suppress Gastric Cancer Growth by Targeting STAT3/Cyclin D1

Datong Jiang1ABCDE, He Li1BC, Heping Xiang1CD, Ming Gao1AB, Chunlin Yin1AD, Haiping Wang1AD, Yuansong Sun1AD, Maoming Xiong2EFG*

DOI: 10.12659/MSM.913087

Med Sci Monit 2019; 25:1537-1548

Abstract

BACKGROUND: Gastric cancer is a common gastrointestinal tumor. The incidence and mortality of gastric cancer are very high. Therefore, it is important to study targeted drugs. Recent studies found long chain non-coding RNA (lncRNAs) and microRNAs (miRNAs) were abnormal in gastric cancer.

MATERIAL AND METHODS: We collected adjacent normal and cancer tissues of gastric cancer patients and measured HOTAIR, miR-454-3p, STAT3, and Cyclin D1 expression and analyzed the correlation with clinical status. We also measured AGS and SGC7901 cells proliferation rate of different groups by MTT assay, and we evaluated AGS and SGC7901 cell apoptosis and cell cycle by flow cytometry. In addition, we assessed the relative proteins expressions by WB assay. Finally, we explored the correlation between miR-454-3p and STAT3 by use of double luciferase reporter.

RESULTS: lncRNA HOTAIR was negatively correlated with miR-454-3p expression in gastric cancer tissues. lncRNA HOTAIR knockdown suppressed AGS and SGC7901, which are gastric cancer cell lines that promote cell proliferation by increasing cell apoptosis and keeping the cell cycle in G1 phase. In further mechanism research, we found that the STAT3 and Cyclin D1 proteins expressions were suppressed by lncRNA HOTAIR down-regulation in AGS and SGC7901 cells.

CONCLUSIONS: Our results suggest that lncRNA HOTAIR knockdown stimulates miR-454-3p expression to inhibit gastric cancer growth by depressing STAT3/Cyclin D1 activity.

Keywords: Cyclin D1, MicroRNAs, RNA, Long Noncoding, STAT3 Transcription Factor, Apoptosis, Cell Movement, Cell Proliferation, Gene Knockdown Techniques, Genes, bcl-1, Stomach Neoplasms

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750