MALAT-1 Is a Key Regulator of Epithelial-Mesenchymal Transition in Cancer: A Potential Therapeutic Target for Metastasis

Simple Summary Metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) is overexpressed in several cancers and exerts its effect by controlling gene expression and stimulating cell proliferation, migration, and metastasis and playing a dynamic role in mediating the epithelial-to-mesenchymal transition (EMT), which leads to the acquisition of stem cell-like properties and chemoresistance. MALAT-1 modulates EMT by interacting with various intracellular signaling pathways, including phosphoinositide 3-kinase (PI3K)/Akt and Wnt/beta-catenin. It also sponges microRNAs, consequently increasing the gene expression of several essential genes regulating cancer progression and metastasis, rendering it a good candidate for therapeutic intervention. Several innovative approaches have been exploited to target MALAT-1, such as short hairpin RNAs (shRNAs), antisense oligonucleotides (ASOs), and natural products.Abstract Metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) is a long intergenic non-coding RNA (lncRNA) located on chr11q13. It is overexpressed in several cancers and controls gene expression through chromatin modification, transcriptional regulation, and post-transcriptional regulation. Importantly, MALAT-1 stimulates cell proliferation, migration, and metastasis and serves a vital role in driving the epithelial-to-mesenchymal transition (EMT), subsequently acquiring cancer stem cell-like properties and developing drug resistance. MALAT-1 modulates EMT by interacting with various intracellular signaling pathways, notably the phosphoinositide 3-kinase (PI3K)/Akt and Wnt/beta-catenin pathways. It also behaves like a sponge for microRNAs, preventing their interaction with target genes and promoting EMT. In addition, we have used bioinformatics online tools to highlight the disparities in the expression of MALAT-1 between normal and cancer samples using data from The Cancer Genome Atlas (TCGA). Furthermore, the intricate interplay of MALAT-1 with several essential targets of cancer progression and metastasis renders it a good candidate for therapeutic interventions. Several innovative approaches have been exploited to target MALAT-1, such as short hairpin RNAs (shRNAs), antisense oligonucleotides (ASOs), and natural products. This review emphasizes the interplay between MALAT-1 and EMT in modulating cancer metastasis, stemness, and chemoresistance in different cancers.