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Comprehensive insights into MACC1-AS1: Role in cancer and therapeutic implications
Chenhao Liang1, Yaojie Feng2, Yuhua Zhang1
1Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, China; Department of Clinical Medicine, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, China.
Abstract:
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.
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