Transmembrane protein 92 performs a tumor-promoting function in breast carcinoma by contributing to the cell growth, invasion, migration and epithelial-mesenchymal transition

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.