Fibulin-2 inhibits development of gastric cancer by downregulating β-catenin

Oncol Lett. 2019 Sep;18(3):2799-2804. doi: 10.3892/ol.2019.10599. Epub 2019 Jul 10.

Abstract

The aim of the present study was to investigate the expression of fibulin-2 and β-catenin in gastric cancer tissues and the association to mutual regulation. Forty-nine cases of gastric cancer specimens obtained via surgical resection in the Pathology Department of Heping Hospital Affiliated to Changzhi Medical College from March 2013 to August 2017 were collected. The expression levels of fibulin-2 and β-catenin in 49 cases of gastric cancer and para-carcinoma tissues were detected via quantitative polymerase chain reaction and immunohistochemistry. The correlation of expression of fibulin-2 and β-catenin proteins in gastric cancer was detected via Spearman's analysis. The correlation of fibulin-2 and β-catenin protein expression with clinicopathological indexes of patients was also analyzed. Moreover, the fibulin-2 overexpression plasmid was constructed and transfected into human gastric cancer AGS and SGC-790 cell lines, so as to observe changes in β-catenin and its downstream indexes. Fibulin-2 messenger ribonucleic acid (mRNA) level in gastric cancer tissues was significantly lower than that in para-carcinoma tissues, while β-catenin mRNA level was significantly increased (P<0.05). The positive rate of fibulin-2 protein was 73.47% (36/49) in gastric cancer tissues and 16.33% (8/49) in para-carcinoma tissues, while that of β-catenin was 77.55% (38/49) in gastric cancer tissues and 28.57% (14/49) in para-carcinoma tissues, indicating that fibulin-2 protein is significantly deleted in gastric cancer tissues, and β-catenin protein is significantly upregulated (P<0.001). Fibulin-2 and β-catenin had a negative correlation (r=-0.361, P=0.003), but was closely correlated with the tumor size and lymph node metastasis (P<0.05). After overexpression of fibulin-2, expression of β-catenin, cyclin D1 and c-Myc protein was obviously downregulated (P<0.05). The tumor suppressor gene, fibulin-2, is significantly deleted in gastric cancer tissues, while β-catenin is remarkably enriched. Overexpression of fibulin-2 can inhibit the development of gastric cancer by downregulating β-catenin.

Keywords: fibulin-2; gastric cancer; tumor suppressor gene; β-catenin.