Long Non-coding RNAs as Regulators of the Mitogen-activated Protein Kinase (MAPK) Pathway in Cancer

BACKGROUND: The mitogen-activated protein kinase (MAPK) pathway contributes to regulation of many cellular functions, such as cell proliferation and differentiation, mobility and apoptosis. Extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) /p38 and ERK5 construct the three main modules in this pathway. The Raf-ERK1/2 and JNK cascades contribute in cell proliferation, migration, and survival and are principal regulators of malignant phenotype. This pathway is itself regulated by several outside signals as well as lateral signals from other pathways, which construct a complex network. Long non-coding RNAs (lncRNAs) as principal modulators of gene expression at transcriptional and post-transcriptional levels also regulate this pathway. In addition, lncRNA signature can be used as biomarker and target of novel treatment strategies in cancer patients. AIM: To explore the role of lncRNAs in regulation of MAPK pathway. CONCLUSION: Considering the role of this pathway in the pathogenesis of several cancers, alterations in lncRNA expression lead to changes in MAPK pathway resulting in inhibition of apoptosis and induction of cell proliferation and migration. Moreover, some lncRNAs participate in cross-talk between MAPK and other cancer-related pathways, such as PI3K/Akt pathway through regulation of certain shared proteins between these pathways. Based on the availability of certain anticancer drugs that modulate this pathway, identification of lncRNAs that affect this pathway would help in establishment of effective therapies.Key words: RNA - long noncoding - mitogen-activated protein kinases - signal transduction.