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RNA-Seq Quantitative Analysis of the regulation of exosomes on metastasis related gene transcriptome in NPC cells

ABSTRACT: In our study, We found that exosomal transfer occurred from highly metastatic nasopharyngeal carcinoma (NPC) cells to poorly metastatic NPC cells mediates cell-cell communication and therefore enhanced metastasis potential and decreased intracellular ROS levels of low metastatic NPC cells. To investigate the detailed mechanism of exosomes derived from highly metastatic NPC cells (H-exo) mediated low metastatic NPC cells metastasis and ROS reduction, low metastatic NPC cells 6-10B and S26 were treated with or without H-exo for RNA-SEQ analysis to exame the expression of metastasis- and ROS-related genes. Our results indicate that the levels of the "leading edge" genes that the majority of these genes correlated with ROS suppressing genes were significantly increased in H-exo treated 6-10B and S26 cells. In contrast, the expression levels of ROS production promoting gene were significantly lower in H-exo treated 6-10B and S26 cells than untreated 6-10B and S26 cells. Meanwhile, the majority of the genes correlated with anti-apoptotic responses and pro-metastasis could be potentially up-regulated by treated 6-10B and S26 cells with H-exo.

ORGANISM(S): Homo sapiens

PROVIDER: GSE149714 | GEO | 2020/05/02

REPOSITORIES: GEO

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Project description:Nasopharyngeal carcinoma (NPC) is known for its high metastatic potential. From genomic expression profiles comparing clones derived from the NPC cell line CNE-2, serglycin (SRGN) was identified as one of the most up-regulated genes in the high-metastasis clone. Serglycin protein was secreted by the high-metastasis clone, but not by any of the low-metastasis clones. Suppression of serglycin by shRNA diminished serglycin secretion and subsequently inhibited the migration and invasion of high-metastasis clone, and also reduced its metastasis rate in vivo. Overexpression of serglycin in low-metastasis cells resulted in an increased metastasis rate in vivo. Moreover, secreted serglycin promoted cellular motility in the wild-type low-metastasis cells. Interestingly, suppression of serglycin reduced the protein level of vimentin but did not influence the level of E-cadherin in high-metastasis clone. Proliferation was not influenced by serglycin in both high-and low-metastasis clones. Clinically, serglycin expression was significantly elevated in liver metastases from NPC relative to its expression in primary tumors. The prognostic value of serglycin was evaluated by immunohistochemical staining of tissue microarrays of NPC tissues from 263 patients, followed by multivariate analyses. A high level of serglycin expression in primary NPC was found to be an independent unfavorable indicator for distant-metastasis-free survival and disease-free survival. In summary, serglycin regulates NPC metastasis via autocrine and paracrine means without influencing proliferation, and it serves as a prognostic indicator of metastasis-free survival and disease-free survival for NPC patients. Keywords: Gene Expression experiment High-metastasis clone (S18) and low-metastasis clones (S22 and S26) together with their parental line CNE-2 were subjected for gene expression profiling to identify the genes highly expressed in high-metastasis clone. To explore the molecular mechanism(s) underlying this important biological behavior, we performed genomic expression profiling of these four cell lines from in vitro cultured cells, as well as in vivo xenograft tumors generated in nude mice by subcutaneous injection of the cells into the BALB/c (nu/nu) female mice. Briefly, 1 × 10^5 cells were subcutaneously injected into the left flank of a nude mouse, and the tumors were collected when their volume was 150-250 mm^3.

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RNA-Seq Quantitative Analysis of the regulation of exosomes on metastasis related gene transcriptome in NPC cells

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