Lung cancer is considered as one of most frequent cancers in the world causing high morbidity and mortality. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) compromise, 80% and 20% of lung carcinoma, respectively. Although many factors such as Tobacco, asbestos, and genetic factors have been associated with lung cancer, the mechanism leading to the development of metastatic adenocarcinoma is not clear. Our recent data on genetically modified mouse model, overexpressing calreticulin under Tie2 promoter showed development of metastatic lung adenocarcinoma in these mice. Calreticulin (CRT) is a ubiquitously expressed protein in mammalian cells, with both calcium binding and chaperone activity. CRT is involved in quality control process during the folding and maturation of protein in endoplasmic reticulum. Histopathology analysis of this mouse models showed a significant similarity of this mouse model to human patients. Furthermore, microarray analysis of lungs from the transgenic mice as compared to the wild type mice, showed a significant increase in a number of long non-coding RNAs. One of these long non-coding RNA (LncRNA) known as Metastasis Associated Lung Adenocarcinoma Transcript-1 (Malat-1) that has been implicated in the development of metastatic lung cancer in human. Malat-1 is a novel Lnc RNA that is localized to nucleus. Furthermore, its 3’ end can be spliced to form tRNA like structure called mascRNA that translocate to cytoplasm. Our data illustrate the involvement of this Lnc RNA in the increased rate of tumor cell migration and altered cell cycle. The exact targets of this Lnc RNA are not known. Using RNA-Seq. analysis of tumor cells after knockdown of Malat-1, we illustrate changes in cluster of genes involved in cell proliferation and migration.
Acknowledgements: This research was supported by a NPRP grant from QNRF (NPRP4-043-3-016)