Regulatory Networks of LncRNA MALAT-1 in Cancer.

Abstract

Long noncoding (lnc)RNAs are a group of RNAs with a length greater than 200 nt that do not encode a protein but play an essential role in regulating the expression of target genes in normal biological contexts as well as pathologic processes including tumorigenesis. The lncRNA metastasis-associated lung adenocarcinoma transcript (MALAT)-1 has been widely studied in cancer. In this review, we describe the known functions of MALAT-1; its mechanisms of action; and associated signaling pathways and their clinical significance in different cancers. In most malignancies, including lung, colorectal, thyroid, and other cancers, MALAT-1 functions as an oncogene and is upregulated in tumors and tumor cell lines. MALAT-1 has a distinct mechanism of action in each cancer type and is thus at the center of large gene regulatory networks. Dysregulation of MALAT-1 affects cellular processes such as alternative splicing, epithelial–mesenchymal transition, apoptosis, and autophagy, which ultimately results in the abnormal cell proliferation, invasion, and migration that characterize cancers. In other malignancies, such as glioma and endometrial carcinoma, MALAT-1 functions as a tumor suppressor and thus forms additional regulatory networks. The current evidence indicates that MALAT-1 and its associated signaling pathways can serve as diagnostic or prognostic biomarker or therapeutic target in the treatment of many cancers.