28 February 2020 : Laboratory Research
Synaptotagmin 12 (SYT12) Gene Expression Promotes Cell Proliferation and Progression of Lung Adenocarcinoma and Involves the Phosphoinositide 3-Kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Pathway
Kaichao Liu12ABE, Jing Luo12ABE, Chenye Shao3BCF, Zhijian Ren2B, Sai Sun4B, Yihao Zhu5A, Hai Zhou36D, Zhisheng Jiang6D, Xiaokun Li7C, Wenfeng Gu12B, Youtao Xu24EG, Yong Qiang6F, Binhui Ren24AG, Lin Xu24AG*, Haiwei Wu16AG, Yi Shen16AGDOI: 10.12659/MSM.920351
Med Sci Monit 2020; 26:e920351
Abstract
BACKGROUND: This study aimed to use bioinformatics analysis to compare data from tissue microarrays from patients with lung adenocarcinoma (LUAD) and normal lung tissue, and human lung adenocarcinoma cells with normal lung epithelial cells in vitro to investigate the role of synaptotagmin 12 (SYT12) gene expression in LUAD.
MATERIAL AND METHODS: Human lung adenocarcinoma cell lines (A549, SPC-A-1, H1299, H1975, and PC9) and the normal HBE cell line were compared, and tumor xenografts were developed in mice. The Cancer Genome Atlas (TCGA) tissue microarray data were used to compare SYT12 expression and overall survival (OS). The in vivo and in vitro effects of down-regulation and upregulation of SYT12 were studied using short-interfering RNA (si-RNA) and overexpression plasmids, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway analysis, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and Western blot investigated the molecular mechanisms of SYT12 expression in LUAD.
RESULTS: SYT12 expression was increased in tissues from patients with LUAD from TCGA and was associated with advanced tumor stage and reduced prognosis. Knockdown of SYT12 suppressed the proliferation and migration of LUAD cells, and upregulation of SYT12 increased the proliferation and migration of LUAD cells in vitro. Phosphorylation of PIK3R3 activated the PI3K/AKT/mTOR pathway. In the mouse xenograft model, expression of SYT12 increased the volume and weight of the xenograft tumors.
CONCLUSIONS: Bioinformatics analysis, human LUAD cells, and mouse xenograft studies showed that SYT12 acted as a possible oncogene by phosphorylation of PIK3R3 to activate the PI3K/AKT/mTOR signaling pathway.
Keywords: Oncogene Protein v-akt, Oncogenes, Phosphatidylinositol 3-Kinases, Adenocarcinoma of Lung, Aged, 80 and over, phosphatidylinositol 3-kinase, Proto-Oncogene Proteins c-akt, Synaptotagmins, TOR Serine-Threonine Kinases
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