Functional roles of lncRNA MALAT1 in acute myeloid leukemia

Acute myeloid leukemia (AML) remains a therapeutic challenge, with high relapse rates following initial treatment, driving the search for novel molecular targets. Emerging evidence highlights the critical role of long non-coding RNAs (lncRNAs) in leukemogenesis, particularly metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). This lncRNA is consistently overexpressed in AML patients and is strongly associated with adverse clinical outcomes, including reduced overall survival. Functionally, MALAT1 acts as a multifaceted oncogenic driver in AML. It promotes leukemia cell proliferation, survival, migration, and chemoresistance through diverse mechanisms. A key function is its role as a competing endogenous RNA (ceRNA), where it “sponges” tumor-suppressive microRNAs. For instance, MALAT1 sequesters miR-146a, leading to upregulation of the C-X-C chemokine receptor type 4 (CXCR4) and enhanced cell survival. Similarly, by binding miR-96, MALAT1 contributes to resistance against Antimetabolite cytosine arabinoside (Ara-C) chemotherapy. Beyond ceRNA activity, MALAT1 exerts epigenetic control by recruiting complexes like Polycomb Repressive Complex 2 (PRC2) to silence tumor suppressors such as E-cadherin, and it can regulate gene expression via interactions with RNA modification machinery. Beyond ceRNA activity, MALAT1 exerts epigenetic control by recruiting complexes like PRC2 to silence tumor suppressors such as E-cadherin, and it can regulate gene expression via interactions with RNA modification machinery. In conclusion, MALAT1 sits at the nexus of a complex regulatory network fundamental to AML pathogenesis and therapy failure. Its involvement in critical processes from microRNA sponging to chromatin remodeling underscores its potential as both a prognostic biomarker and a promising therapeutic target for overcoming drug resistance and improving patient outcomes in AML.