Abstract 2343: Role of calreticulin in the regulation of MALAT-1 expression in mouse adenocarcinoma cells

Calreticulin (CRT) is a ubiquitously expressed protein, with both calcium binding and chaperone activity. CRT is involved in quality control process during the folding and maturation of proteins in ER. Recently, we showed that overexpression of CRT resulted in the development of metastatic lung adenocarcinoma. In order to examine genes involved in the development of lung cancer we carried out microarray analysis on RNA isolated from mouse lung tumors versus control. In this screen we observed a significant increase in long noncoding RNA (LncRNA) MALAT-1 in the lungs of CRT overexpressing mouse models. MALAT-1 is a LncRNA that has been documented to be upregulated in the human lung adenocarcinoma and associated with metastasis. Our study was to investigate the mechanism of regulation of MALAT-1 expression and role of CRT in this process. We hypothesized that CRT as a regulator of intracellular calcium regulated MALAT-1 expression thus inducing the development of metastatic lung adenocarcinoma in our mice model. Our data showed a significant correlation between intracellular calcium levels and MATAT-1 RNA expression and stability. Treatment of adenocarcinoma cells with BAPTA-AM resulted in a significant reduction in MALAT-1 level. Treating the cells with thapsigargin induced a 2 fold increase in MALAT-1 expression. We also demonstrated that knock down of MALA-1 expression using specific siRNA reduces the proliferation of adenocarcinoma cell. Our data demonstrate for the first t...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Molecular and Cellular Biology Source Type: research