High expression of TFEB is associated with aggressive clinical features in colorectal cancer

Onco Targets Ther. 2018 Nov 13:11:8089-8098. doi: 10.2147/OTT.S180112. eCollection 2018.

Abstract

Objectives: The transcription factor EB (TFEB), a member of the micropthalmia family, has been found to be associated with autophagy and upregulated in some kinds of tumors. However, very few studies focused on TFEB in colorectal cancer (CRC). TFEB expression status and its relevance to clinical features in CRC would be analyzed in this study.

Materials and methods: Real-time PCR, Western blot, and immunohistological staining were used to evaluate TFEB expression in CRC tissues and adjacent normal tissues, and the role of TFEB in CRC cell lines was investigated in vitro and in vivo.

Results: TFEB was expressed at lower level in CRC tissues than normal in both mRNA and protein level. However, there were significantly positive correlations between TFEB expression in cancer tissues and malignant progression of CRC. Cancers with TFEB overexpression always had deeper infiltration and higher lymphatic metastasis rate. Furthermore, patients with high TFEB levels always had poor survival, and higher TFEB expression could be a predictor of survival in multivariate analysis. Meanwhile, knockdown TFEB by shRNA or knockout TFEB by sgRNA in CRC cell lines could significantly inhibit cell proliferation and migration in amino acid-free medium. In addition, we found a positive relationship between TFEB and Beclin1 expression, and silencing TFEB inhibited Beclin1 expression in CRC cells.

Conclusion: TFEB expression correlated with aggressive clinical features in CRC, and higher TFEB expression could be a prognostic factor and potential treatment target of CRC.

Keywords: Beclin1; TFEB; clinicopathologic variables; colorectal cancer; prognostic factor.