Head and Neck Cancer

PV QA 2 - Poster Viewing Q&A 2

MO_29_2693 - Siglec-8 Inhibits Malignancies via Mitochondria-dependent Apoptosis Pathway in Nasopharyngeal Carcinoma

Monday, October 22
10:45 AM - 12:15 PM
Location: Innovation Hub, Exhibit Hall 3

Siglec-8 Inhibits Malignancies via Mitochondria-dependent Apoptosis Pathway in Nasopharyngeal Carcinoma
Z. Le, Y. Liu, W. Tu, J. Li, S. Yao, Z. Wang, Y. Xu, T. Chen, G. Zhao, and Q. Huang; Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Purpose/Objective(s): Siglec-8 (Sialic acid–binding immunoglobulin-like lectin 8) is principally expressed and mediated apoptosis on human eosinophils. Our recent study showed that Siglec-8 is one of the direct targets of miR-663a, a significantly up-regulated miRNA screened from microarray of NPC cells. The goal of this study was to further investigate the potential effect of Siglec-8 against nasopharyngeal carcinoma (NPC).

Materials/Methods: 70 formalin-fixed paraffin-embedded (FFPE) NPC tissues were collected to evaluate the association between Siglec-8 expression and prognosis of patients with NPC. An external cohort of 566 patients with HNSCC from TCGA dataset were used for further validation. CCK-8, wound healing, transwell, soft agar colony formation and apoptosis assays, and a xenograft tumor model were used to determine the role of Siglec-8 in NPC progression. Immunohistochemistry(IHC), western blot and Human Apoptosis Antibody Array were used to detect protein expression changes caused by Siglec-8 silencing in NPC cell lines or tumor tissues.

Results: By immunohistochemical analysis, Siglec-8 was highly expressed in 31(44.3%) of 70 NPC patients. No significant correlations were found between Siglec-8 expression levels and patient gender, age or tumor stage. Statistical analysis showed higher expression of Siglec-8 is significantly correlate with better overall survival (OS) in patients with NPC (p = 0.015, HR = 1.89; 95% CI: 1.14-3.24). And this finding is validated by external TCGA HNSCC dataset (p = 0.033). Functional assays revealed Siglec-8 knockdown significantly enhanced NPC cells proliferation, migration and invasion in vitro. In xenograft tumour models, the tumour volumes and weights were significantly increased following Siglec-8 silenced. IHC staining found that low expression of Siglec-8 enhanced the aggressive phenotype of NPC as indicated by up-regulated Ki67 and Vimentin and down-regulated E-cadherin, Tunel, cleaved capsase-3 and cleaved capsase-8. These findings were validated by western blot. Moreover, Siglec-8 knockdown suppressed cell apoptosis and ROS production in CNE-2Z cells, accompanied by decreased expression of Bax, Cytochrome c and cleaved caspase-3.

Conclusion: Our results show that the expression of Siglec-8 is related to survival in NPC patients and down-regulation of Siglec-8 contributes to tumor progression and inhibition of mitochondrial-dependent apoptosis. We suggested that Siglec-8 may be a valuable maker of NPC progression although its value in clinical application needs to be further verified.

Author Disclosure: Z. Le: None. Y. Liu: None. Z. Wang: None. Q. Huang: None.

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