Stress induced phosphoprotein 1 overexpression controls proliferation, migration and invasion and is associated with poor survival in oral squamous cell carcinoma

应激诱导的磷蛋白 1 过度表达控制增殖、迁移和侵袭,并与口腔鳞状细胞癌的低生存率相关

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作者:Mauricio Rocha Dourado, Amr Elseragy, Bruno Cesar da Costa, Fábio Haach Téo, Gustavo Narvaes Guimarães, Renato Assis Machado, Maija Risteli, Wafa Wahbi, Clarissa Araujo Gurgel Rocha, Lívia Máris Ribeiro Paranaíba, Wilfredo Alejandro González-Arriagada, Sabrina Daniela da Silva, Ana Lucia Carrinho Ay

Conclusion

Our findings show that STIP1 overexpression, which is inversely associated with miR-218-5p levels, contributes to OSCC aggressiveness by controlling proliferation, migration and invasion and is a determinant of poor prognosis.

Methods

STIP1 expression was assessed in the TCGA database and in two independent cohorts by immunohistochemistry. Knockdown strategy was applied in OSCC cell lines to determine the impact of STIP1 on viability, proliferation, migration and invasion. The zebrafish model was applied for studying tumor formation and metastasis in vivo. The association of STIP1 and miR-218-5p was explored by bioinformatics and mimics transfection.

Objective

Although there have been remarkable achievements in the molecular landscape of oral squamous cell carcinoma (OSCC) in recent years, bringing advances in the understanding of its pathogenesis, development and progression, little has been applied in the prognosis and choosing the optimal treatment. In this study, we explored the influence of the stress induced phosphoprotein 1 (STIP1), which is frequently reported to be highly expressed in many cancers, in OSCCs.

Results

STIP1 was highly expressed in OSCCs and significantly associated with shortened survival and higher risk of recurrence. STIP1 down-regulation decreased proliferation, migration and invasion of tumor cells, and reduced the number of metastases in the Zebrafish model. STIP1 and miR-218-5p were inversely expressed, and the transfection of miR-218-5p mimics into OSCC cells decreased STIP1 levels as well as proliferation, migration and invasion.

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