Oncogenic roles and mechanisms of lncRNA AGAP2-AS1 in human solid tumors

Abstract

Cancer remains the second leading life-threatening disease worldwide. Increasing evidence indicates that long non-coding RNAs (lncRNAs) play an important role in multiple physiological and pathological processes, including gene amplification, mutation, rearrangement, and overexpression regulations. In this review, we comprehensively summarize the current knowledge of lncRNA AGAP2-AS1 from a cancer perspective. As a member of the lncRNA family, lncRNA AGAP2-AS1 is upregulated in solid tumor malignancies, functions as an oncogene, and plays a key role in tumorigenesis and tumor progression. AGAP2-AS1 expression is significantly increased in clinical cancer tissue samples, cell lines, and in vivo, and is closely related to an unfavorable prognosis in several cancers. Upregulated lncRNA AGAP2-AS1 binds with microRNAs (miRNAs) and promotes activation of downstream genes. This aberrant regulation induces carcinogenesis and tumorigenesis. Here we provide a comprehensive overview of AGAP2-AS1 in cancer progression that leads to an improved understanding of the effects of AGAP2-AS1 on early detection and therapeutic approaches. This information is essential for the future development of lncRNA AGAP2-AS1 as a potential therapy against these devastating cancers.

Keywords: AGAP2-AS1; cancers; lncRNAs; oncogene.

Figure 1

The gene expression level of lncRNA AGAP2-AS1 in various cancers. A-H. LncRNA AGAP2-AS1 is significantly upregulated in tumor tissue compared with adjacent tumor tissue (CHOL, COAD, ESCA, HNSC, KIRC, LUSC, PCPG, and STAD). I. LncRNA AGAP2-AS1 is downregulated in UCEC tumor tissue compared with para-tumor tissue.

Figure 2

The prognostic value of lncRNA AGAP2-AS1 in various cancers. A-I. The highly expressed lncRNA AGAP2-AS indicated unfavorable prognosis in various cancers such as ACC, BLCA, GMB, KIRC, LGG, LUAD, MESO, SKCM, and THCA.

Figure 3

The regulatory mechanism of LncRNA AGAP2-AS1 in cancer cell. AGAP2-AS1 act as a sponge targeting downstream micro-RNAs, such as miR-628-5p, miR-15a/b-5p, miR-497, miR-4668-3p, and miR-16-5p. The downstream target genes, such as PTN, HDGF, FGFR1, SRSF1, FOSL1, and ANXA11/AKT, are dysregulated. The carcinogenesis and tumorigenesis related pathways are activated. LncRNA AGAP2-AS1 promotes cancer cell proliferation, invasion, migration, EMT, and inhibit tumor apoptosis.

Figure 4

The lncRNA AGAP2-AS1 knockdown cells are transferred into xenograft. The knockdown AGAP2-AS1 slows down tumor growth, inhibits tumor volume and weight compared with normal control xenograft model.