Objective

We try to examine the role of transmembrane protein 92 (TMEM92) in the progression of breast carcinoma (BC) and assess its prognostic value. Moreover, the effects of TMEM92 on BC cell phenotypes was explored.

Methods

The levels of TMEM92 in BC tissues were evaluated using bioinformatics analysis according to the Oncomine and The Cancer Genome Atlas databases. mRNA levels of TMEM92 in BC cells were measured by qRT-PCR. Kaplan-Meier methods together with log-rank tests were used to conduct survival analysis, and chi-square tests were employed to assess the relationship between TMEM92 levels and clinicopathological parameters. Cox regression analysis was carried out to identify the independent prognosticators. Small interference RNA targeted to TMEM92 and plasmid vectors pcDNA3.1-TMEM92 were respectively used to silence and over-express TMEM92. Protein levels of molecules in this study were tested by western blot. Cell viability, invasiveness and motility of BC cells were determined by cell counting kit 8, clone formation assay and Transwell assay, appropriately.

Results

The data showed that TMEM92 was upregulated in BC tissues or cells in comparison with control. High expression of TMEM92 was notably correlated with stage and metastasis, and led to a poor overall survival. Moreover, cox multivariate analysis model demonstrated that TMEM92 can be seen as an independent prognostic factor. Functional experiments demonstrated that downregulation of TMEM92 showed a significantly inhibitory effect on MDA-MB-231 cell viability, invasiveness and motility, whereas overexpression of TMEM92 could promote the changes of these phenotypes. Furthermore, western blot analysis revealed that depletion of TMEM92 inactivated the epithelial-mesenchymal transition (EMT) process with raised E-cadherin protein levels, while declined N-cadherin, Vimentin and Snail levels. However, enhancement of TMEM92 showed the opposite outcomes on these EMT-related markers.

Conclusion

TMEM92 had an independent prognostic value for BC patients, and might act as an oncogene to facilitate tumor cells growth, invasiveness and motility by modulating the EMT relative proteins.

中文翻译：

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跨膜蛋白 92 通过促进细胞生长、侵袭、迁移和上皮间质转化，在乳腺癌中发挥促进肿瘤的作用。

客观的

我们尝试检查跨膜蛋白 92 (TMEM92) 在乳腺癌 (BC) 进展中的作用并评估其预后价值。此外，还探讨了 TMEM92 对 BC 细胞表型的影响。

方法

根据 Oncomine 和癌症基因组图谱数据库，使用生物信息学分析评估 BC 组织中 TMEM92 的水平。通过qRT-PCR测量BC细胞中TMEM92的mRNA水平。Kaplan-Meier方法结合log-rank检验进行生存分析，卡方检验评估TMEM92水平与临床病理参数之间的关系。进行 Cox 回归分析以确定独立的预后因素。靶向 TMEM92 的小干扰 RNA 和质粒载体 pcDNA3.1-TMEM92 分别用于沉默和过表达 TMEM92。本研究中分子的蛋白质水平通过蛋白质印迹测试。BC 细胞的细胞活力、侵袭性和运动性通过细胞计数试剂盒 8、克隆形成试验和 Transwell 试验适当地确定。

结果

数据显示，与对照相比，TMEM92 在 BC 组织或细胞中上调。TMEM92 的高表达与分期和转移显着相关，并导致较差的总生存率。此外，cox 多变量分析模型表明 TMEM92 可被视为独立的预后因素。功能实验表明，TMEM92 的下调对 MDA-MB-231 细胞活力、侵袭性和运动性具有显着抑制作用，而 TMEM92 的过表达可促进这些表型的变化。此外，蛋白质印迹分析显示，TMEM92 的消耗使上皮间充质转化 (EMT) 过程失活，E-钙粘蛋白水平升高，而 N-钙粘蛋白、波形蛋白和蜗牛水平下降。然而，

结论

TMEM92 对 BC 患者具有独立的预后价值，并且可能作为致癌基因通过调节 EMT 相关蛋白来促进肿瘤细胞的生长、侵袭和运动。