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RNA-Seq quantitative analysis of the regulation of platelet-derived extracellular vesicles on NPC cells transcriptomes

ABSTRACT: Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor with a high metastatic feature and invasive nature. The survival rate of NPC patients is still very low due to the high incidence of distant metastasis. Platelets are versatile blood cells and mediate the distant metastasis of tumor cells via the blood circulation. However, the role and underlying mechanism of platelets responsible for the NPC cells hematogenous metastasis are not well understood. In our study, we found that platelet-derived EVs of NPC patients (P-EVs) induced the metastasis and mesenchymal-epithelial transition process in NPC cells. To shed light on the mechanism underlying P-EVs-induced NPC metastasis and MET process, we performed high throughput RNA-Seq analyses to reveal the differentially expressed genes in NPC cells treated with or without P-EVs. We observed that there was a significant overlap in the expression of integrins that were altered in 6-10B and 5-8F upon P-EVs treatment. Of these, integrin β3 (ITGB3) exhibited the most obvious upregulation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE196879 | GEO | 2022/02/23

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 platelet-derived extracellular vesicles on NPC cells transcriptomes

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