Comprehensive insights into MACC1-AS1: Role in cancer and therapeutic implications

Long non-coding RNAs (lncRNAs) are a diverse class of non-coding transcripts longer than 200 nucleotides that play critical roles in gene regulation and disease progression. Among them, MACC1 antisense RNA 1 (MACC1-AS1), located on chromosome 7p21.1, is transcribed in antisense orientation to the metastasis-associated in colon cancer-1 (MACC1) gene. MACC1-AS1 is significantly overexpressed in ten types of cancers and is associated with poor prognosis and clinical characteristics. MACC1-AS1 is transcriptionally or post-transcriptionally regulated by upstream modulators such as interferon-γ (IFN-γ), polypyrimidine tract-binding protein 1 (PTBP1), Smad2, transforming growth factor-β1 (TGF-β1), and Kras. In turn, MACC1-AS1 influences downstream effectors through three principal molecular mechanisms: acting as a competitive endogenous RNA (ceRNA) to modulate the microRNA (miRNA)–mRNA axis, binding antisense to MACC1 mRNA, and regulating transcription factors as well as downstream protein expression. MACC1-AS1 participates in multiple cellular signaling pathways, including AMPK, Hippo, PI3K/AKT, and Notch1 pathways. MACC1-AS1 modulates proliferation, apoptosis, epithelial–mesenchymal transition (EMT), invasion, migration, and the maintenance of cancer stemness. Moreover, MACC1-AS1 contributes to therapeutic resistance, conferring reduced sensitivity to chemotherapeutic agents such as 5-fluorouracil (5-FU), oxaliplatin, gemcitabine, and cisplatin, as well as to combination regimens including 5-fluorouracil and oxaliplatin (FOLFOX). This review provides an overview of the current knowledge surrounding MACC1-AS1 and highlights its potential as both a biomarker and a therapeutic target for future translational research.