MALAT1 as a molecular driver of tumor progression, immune evasion, and resistance to therapy

Abstract

Long noncoding RNAs (lncRNAs) are emerging as important regulators of gene expression in both normal biological systems and disease. Among them, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has attracted considerable attention due to its high nuclear expression and evolutionary conservation. It was first identified as a biomarker for lung cancer metastasis, but since then, its involvement has been reported in a wide range of cancers. MALAT1 influences several key cancer-related processes, including cell proliferation, migration, angiogenesis, apoptosis, epithelial–mesenchymal transition, and the behavior of cancer stem cells. In this review, we take a closer look at how MALAT1 functions through different mechanisms, such as regulating RNA splicing, altering chromatin states, acting as a sponge for microRNAs, or modifying protein interactions, to drive these changes. We also discuss its growing role in shaping the immune landscape of tumors, particularly its involvement in immune evasion, inflammatory signaling, and regulation of immunogenic cell death. In addition, MALAT1 contributes to resistance against therapy, rewiring of cellular metabolism, and communication between tumor and stromal cells via exosomes. While many studies describe MALAT1 as an oncogene, others suggest it may also play a suppressive role depending on the cancer type and biological context. Here, we aim to offer a comprehensive overview of MALAT1’s diverse actions and evaluate its potential as a diagnostic marker and therapeutic target in cancer.