| Summary: | 碩士 === 義守大學 === 生物科技學系 === 104 === The long-non coding RNAs (lncRNAs) are a group of non-protein coding transcripts, which are more than 200 nucleotides in length. Accumulating evidences showed that lncRNAs play critical role in cancer progression, including cell growth, cell cycle, apoptosis and metastasis. Metformin shows the potential as a preventive and therapeutic drug for human cancers. Previous studies indicated that metformin suppressed cancer cerll growth by regulating protein coding genes and microRNAs (miRNA). However, the role of lncRNA involved in metformin-induced inhibition of cell growth and its biological function in gastric cancer remains largely unknown. In this study, we like to identify metformin-associated lncRNAs in gastric cancer cell. Our results showed that metformin could significantly suppress gastric cancer cell growth via inducing cell cycle arrest at G2/M phase. In order to study detail mechanism, we performed the transcriptome profiles of HR cell with/without metformin treatment, adjacent normal tissues and cancer tissues form two gastric cancer patients using microarray approach. Our data revealed that 4,160 genes upregulated and 3,383 genes downregulated in HR cell with metformin treatment. Using pathway enrichment analysis revealed that these metformin-associated genes significantly involved in cell cycle-relative pathway.
Among these metformin-regulating genes, these are 61 protein-coding genes and 20 lncRNAs were downregulated in gastric cancer compared to adjacent normal tissues, but upregulated in HR after metformin treatment. Furthermore, 61 protein-coding genes and 7 lncRNAs upregulated in gastric cancer, but downregulated in HR cell by metformin treatment. Among them, the oncogenic lncRNA, Loc10050669, was selected to further examine in our study. The expression levels of Loc10050669 were decreased in dose- and time course-dependent manner after gastric cancer cells treatment with metformin. Moreover, Loc100506691 were significant overexpression in gastric cancer compared to adjacent normal tissues (P<0.001). Knockdown of Loc10050669 expression could significantly suppress gastric cancer cell growth and induce cell cycle arrest at G2/M phase. Furthermore, Loc100506691 knockdown also significantly suppressed cell invasion ability in gastric cancer cells. Our findings concluded that anti-proliferative effects of metformin in gastric cancer may result partly from induction of cell cycle arrest at G2/M by suppressing loc100506691 expression.
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