Affiliation:
1. Applied Cellular and Molecular Research Center Kerman University of Medical Sciences Kerman Iran
2. Department of Immunology, School of Medicine Kerman University of Medical Sciences Kerman Iran
3. Department of Immunology, School of Medicine Rafsanjan University of Medical Sciences Rafsanjan Iran
4. Immunology Research Center Tabriz University of Medical Sciences Tabriz Iran
5. Student Research Committee, Faculty of Medicine Kerman University of Medical Sciences Kerman Iran
6. Cancer Immunology and Immunotherapy Research Center Ardabil University of Medical Sciences Ardabil Iran
7. Department of Immunology, School of Medicine Shahid Beheshti University of Medical Sciences Tehran Iran
8. Department of Hematology and Laboratory Sciences, School of Para‐Medicine Kerman University of Medical Sciences Kerman Iran
Abstract
ABSTRACTApelin, a bioactive peptide that serves as an endogenous ligand for the apelin receptor (APJ), is overexpressed in various types of cancers and contributes to cancer cell proliferation, viability, migration, angiogenesis, and metastasis, as well as immune deviation. Noncoding RNAs (ncRNAs) regulate gene expression, and there is growing evidence suggesting a bidirectional crosstalk between ncRNAs (including long noncoding RNAs [lncRNAs], circular RNAs [circRNAs], and microRNAs [miRNAs]) and apelin in cancers. Certain miRNAs can directly target the apelin and inhibit its expression, thereby suppressing tumor growth. It has been indicated that miR‐224, miR‐195/miR‐195‐5p, miR‐204‐5p, miR‐631, miR‐4286, miR‐637, miR‐4493, and miR‐214‐3p target apelin mRNA and influence its expression in prostate cancer, lung cancer, esophageal cancer, chondrosarcoma, melanoma, gastric cancer, glioma, and hepatocellular carcinoma (HCC), respectively. Moreover, circ‐NOTCH1, circ‐ZNF264, and lncRNA BACE1‐AS upregulate apelin expression in gastric cancer, glioma, and HCC, respectively. On the other hand, apelin has been shown to regulate the expression of certain ncRNAs to affect tumorigenesis. It was revealed that apelin affects the expression of circ_0000004/miR‐1303, miR‐15a‐5p, and miR‐106a‐5p in osteosarcoma, lung cancer, and prostate cancer, respectively. This review explains a bidirectional interplay between ncRNAs and apelin in cancers to provide insights concerning the molecular mechanisms underlying this crosstalk and potential implications for cancer therapy.