Dourado Mauricio Rocha, Elseragy Amr, da Costa Bruno Cesar, Téo Fábio Haach, Guimarães Gustavo Narvaes, Machado Renato Assis, Risteli Maija, Wahbi Wafa, Gurgel Rocha Clarissa Araujo, Paranaíba Lívia Máris Ribeiro, González-Arriagada Wilfredo Alejandro, da Silva Sabrina Daniela, Rangel Ana Lucia Carrinho Ayroza, Marques Marcelo Rocha, Rossa Junior Carlos, Salo Tuula, Coletta Ricardo D
Department of Oral Diagnosis, and Graduate Program in Oral Biology, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil.
Cancer and Translational Medicine Research Unit, Faculty of Medicine, and Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland.
Front Oncol. 2023 Jan 11;12:1085917. doi: 10.3389/fonc.2022.1085917. eCollection 2022.
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.
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 . The association of STIP1 and miR-218-5p was explored by bioinformatics and mimics transfection.
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.
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.
尽管近年来口腔鳞状细胞癌（OSCC）的分子图谱研究取得了显著成就，在其发病机制、发展和进展的认识上有了进展，但在预后和选择最佳治疗方法方面应用较少。在本研究中，我们探讨了应激诱导磷蛋白1（STIP1）在OSCC中的影响，STIP1在许多癌症中经常被报道高表达。
通过免疫组织化学在TCGA数据库和两个独立队列中评估STIP1表达。在OSCC细胞系中应用敲低策略来确定STIP1对活力、增殖、迁移和侵袭的影响。应用斑马鱼模型研究肿瘤形成和转移。通过生物信息学和模拟转染探索STIP1与miR-218-5p的关联。
STIP1在OSCC中高表达，与缩短的生存期和更高的复发风险显著相关。STIP1下调降低了肿瘤细胞的增殖、迁移和侵袭，并减少了斑马鱼模型中的转移数量。STIP1和miR-218-5p呈反向表达，将miR-218-5p模拟物转染到OSCC细胞中可降低STIP1水平以及增殖、迁移和侵袭。
我们的研究结果表明，STIP1过表达与miR-218-5p水平呈负相关，通过控制增殖、迁移和侵袭促进OSCC的侵袭性，是预后不良的决定因素。
