Expression profile, regulatory mechanism and prognostic potential of MBNL2 in esophageal squamous cell carcinoma.

Background: It remains to refresh the understanding about the pathogenic mechanism of esophageal squamous cell carcinoma (ESCC). This study aimed to profile the expression of muscleblind like protein 2 (MBNL2), as well as its associations with ESCC behaviors.

Methods: Bioinformatic tools were used to mine The Cancer Genome Atlas (TCGA) database for the expression data of MBNL2 in ESCC. The expression of MBNL2 in tissue microarray of 179 ESCC patients was determined by immunohistochemistry (IHC), and the relationship of MBNL2 with patients' clinical and pathological characteristics was analyzed. The expression of MBNL2 was tested in fresh ESCC and adjacent normal tissues in vitro. Experiments about cellular invasion, migration and proliferation were performed to detect the impacts of silencing MBNL2 on the biological behaviors of ESCC, and the positive results were checked in vivo.

Results: In the TCGA database, the expression of MBNL2 in ESCC was higher than that in adjacent tissues (P<0.05). The protein level of MBNL2 in the tissue microarray of 179 ESCC patients was positively correlated with tumor stage and lymph node metastasis, and negatively correlated with the prognosis of patients. The expression of MBNL2 was significantly upregulated in five fresh ESCC tissues, compared to that in adjacent tissues. In functional experiments, knocking down MBNL2 significantly inhibited the migration and invasion of ESCC cell lines KYSE150 and Eca109, but had no significant effect on their proliferation. Finally, silencing MBNL2 inhibited the epithelial-mesenchymal transition (EMT) of ESCC cells, as evidenced by the upregulation of E-cadherin, the downregulation of Snail and Slug.

Conclusions: MBNL2 is highly expressed in ESCC and associated with its Tumor Node Metastasis (TNM) stage, lymph node metastasis and prognosis. MBNL2 may promote ESCC progression through facilitating EMT.