Xiuling Liu1, Weixia Zhao2, Xuehai Wang3. 1. Department of Otolaryngology Head and Neck Surgery, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai 264200, Shandong, PR China. Electronic address: liuxiul000@163.com. 2. Department of Otolaryngology, Weihai Central Hospital, Weihai 264200, Shandong, PR China. 3. Department of Otolaryngology Head and Neck Surgery, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai 264200, Shandong, PR China.
Abstract
OBJECTIVE: Hypopharyngeal squamous cell carcinoma (HSCC) is a common type of malignant tumor. Long non-coding RNAs (lncRNAs) are known to participate in HSCC development, while the role of lncRNA MALAT1 in HSCC remains largely unknown. We aimed to explore function of the lncRNA MALAT1/miR-429/ZEB1 axis in HSCC progression. METHODS: Levels of MALAT1, miR-429 and ZEB1 in HSCC tissues samples were assessed. The FaDu cells were respectively treated with relative sequence or plasmid of MALAT1, miR-429, or ZEB1. Then, CCK-8 assay, colony formation assay, flow cytometry and Transwell assay were used to determine the cell proliferation, apoptosis, cell cycle, migration and invasion of the cells. The PI3K/Akt/mTOR signaling pathway-related proteins, proliferation-related proteins, cell cycle-related proteins, apoptosis-related proteins, and migration-related proteins were detected using Western blot analysis. The cell growth in vivo was observed. The targeting relationships between MALAT1 and miR-429, and between miR-429 and ZEB1 were confirmed. RESULTS: MALAT1 and ZEB1 expression in HSCC was upregulated while miR-429 expression was downregulated. Reduced MALAT1 and ZEB1, and upregulated miR-429 inactivated the PI3K/Akt/mTOR signaling pathway, suppressed in vitro viability, colony formation ability, migration and invasion, as well as cell growth in vivo, and promoted the apoptosis of FaDu cells. Downregulated miR-429 reversed the role of MALAT1 inhibition in FaDu cell growth. LncRNA MALAT1 served as a sponge of miR-429, thus regulating ZEB1 expression. CONCLUSION: Inhibition of MALAT1 was able to elevate miR-429 to suppress the progression of HSCC via reducing ZEB1. Our research provided a potential therapeutic target for HSCC.
OBJECTIVE:Hypopharyngeal squamous cell carcinoma (HSCC) is a common type of malignant tumor. Long non-coding RNAs (lncRNAs) are known to participate in HSCC development, while the role of lncRNA MALAT1 in HSCC remains largely unknown. We aimed to explore function of the lncRNA MALAT1/miR-429/ZEB1 axis in HSCC progression. METHODS: Levels of MALAT1, miR-429 and ZEB1 in HSCC tissues samples were assessed. The FaDu cells were respectively treated with relative sequence or plasmid of MALAT1, miR-429, or ZEB1. Then, CCK-8 assay, colony formation assay, flow cytometry and Transwell assay were used to determine the cell proliferation, apoptosis, cell cycle, migration and invasion of the cells. The PI3K/Akt/mTOR signaling pathway-related proteins, proliferation-related proteins, cell cycle-related proteins, apoptosis-related proteins, and migration-related proteins were detected using Western blot analysis. The cell growth in vivo was observed. The targeting relationships between MALAT1 and miR-429, and between miR-429 and ZEB1 were confirmed. RESULTS:MALAT1 and ZEB1 expression in HSCC was upregulated while miR-429 expression was downregulated. Reduced MALAT1 and ZEB1, and upregulated miR-429 inactivated the PI3K/Akt/mTOR signaling pathway, suppressed in vitro viability, colony formation ability, migration and invasion, as well as cell growth in vivo, and promoted the apoptosis of FaDu cells. Downregulated miR-429 reversed the role of MALAT1 inhibition in FaDu cell growth. LncRNA MALAT1 served as a sponge of miR-429, thus regulating ZEB1 expression. CONCLUSION: Inhibition of MALAT1 was able to elevate miR-429 to suppress the progression of HSCC via reducing ZEB1. Our research provided a potential therapeutic target for HSCC.
Authors: Przemysław A Stempor; Dror Avni; Raya Leibowitz; Yechezkel Sidi; Maria Stępień; Tomasz Dzieciątkowski; Paula Dobosz Journal: Int J Mol Sci Date: 2021-03-04 Impact factor: 5.923