Abstract
Long noncoding RNAs (lncRNAs) have been identified as contributors to the development and progression of cancer through various functions and mechanisms. LncRNA GAS5 is downregulated in multiple cancers and acts as a tumor suppressor in breast cancer. GAS5 interacts with various proteins (e.g., E2F1, EZH2, and YAP), DNA (e.g., the insulin receptor promoter), and various microRNAs (miRNAs). In breast cancer, GAS5 binds with miR-21, miR-222, miR-221-3p, miR-196a-5p, and miR-378a-5p that indicates the presence of several elements for miRNA binding (MREs) in GAS5. Mediated by the listed miRNAs, GAS5 is involved in the upregulation of a number of mRNAs of suppressor proteins such as PTEN, PDCD4, DKK2, FOXO1, and SUFU. Furthermore, the aberrant promoter methylation is involved in the regulation of GAS5 gene expression in triple-negative breast cancer and some other carcinomas. GAS5 can stimulate apoptosis in breast cancer via diverse pathways, including cell death receptors and mitochondrial signaling pathways. GAS5 is also a key player in the regulation of some crucial signal pathways in breast cancer, such as PI3K/AKT/mTOR, Wnt/β-catenin, and NF-κB signaling. Through epigenetic and other mechanisms, GAS5 can increase sensitivity to multiple drugs and improve prognosis. GAS5 is thus a promising target in the treatment of breast cancer patients.
Highlights
growth arrest-specific 5 (GAS5) belongs to the 50 -terminal oligopyrimidine (50 -TOP) gene family, which includes genes that encode all ribosomal proteins, the elongation factors of protein synthesis, and many other genes not associated with ensuring the functional activity of ribosomes [21]
All of the aforementioned information supports the conclusion that GAS5 promotes apoptosis, suppresses metastasis, enhances sensitivity to a number of drugs, and increases the survival rate of breast cancer patients, including triple-negative breast cancer (TNBC), through the participation of some mechanisms according to the competitive endogenous RNA (ceRNA) model (Figure 2)
LncRNA GAS5 is involved in the epigenetic regulation of genes, miRNAs, and proteins
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Many lncRNA genes are oncogenes whose expression levels are increased in tumors compared to matched non-cancerous tissues from the same patient [2]. Another group of genes that encode suppressor lncRNAs are downregulated in tumors and suppress tumor growth and progression [2]. GAS5 belongs to the 50 -terminal oligopyrimidine (50 -TOP) gene family, which includes genes that encode all ribosomal proteins, the elongation factors of protein synthesis, and many other genes not associated with ensuring the functional activity of ribosomes [21]. The remainder of this subsection provides a brief overview of the main aspects of GAS5 cell functions and their relationship with certain structural elements of the gene and its lncRNA (Figure 1)
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