IGFBP-2 in cervical cancer development

Abstract

Increased expression of insulin-like growth factor binding protein 2, IGFBP-2, is associated with many cancers, though its role in cervical cancer is unclear. The aim of this study was to investigate the expression of IGFBP-2 protein and the transcriptomics profile of genes involved in the IGF signaling pathway during cervical cancer development. Design: Immunohistochemical expression of IGFBP-2 protein was semi-quantitatively assessed in tissue microarrays containing 9 normal cervix, 10 low grade cervical intraepithelial neoplasia (LGCIN), 10 high grade cervical intraepithelial neoplasia (HGCIN) and 42 squamous cell carcinoma (SCC) cases. The gene expression profiles of IGFBP-2, IGF-1, IGF-1R, PTEN, MDM2, AKT1 and TP53 were determined in three cervical tissue samples each from normal cervix, human papillomavirus (HPV)-infected LGCIN, HGCIN and SCC, using Human Transcriptome Array 2.0. Results: IGFBP-2 protein was highly expressed in the cytoplasm of SCC cells compared to normal cervix (p = .013). The expression was not significantly associated with CIN grade or SCC stage. Transcriptomics profiling demonstrated upregulation of IGFBP-2 and TP53 in HGCIN and SCC compared to normal cervix. IGF-1, IGF-1R and PTEN genes were downregulated in all histological groups. IGF-1 gene was significantly downregulated in SCC (p = .031), while PTEN gene was significantly downregulated in HGCIN (p = .012), compared to normal cervix. MDM2 and AKT1 genes were downregulated in LGCIN and HGCIN, while upregulated in SCC. Conclusion: In cervical carcinogenesis, IGFBP-2 appears to play an oncogenic role, probably through an IGFindependent mechanism.

LINC00861 inhibits the progression of cervical cancer cells by functioning as a ceRNA for miR‑513b‑5p and regulating the PTEN/AKT/mTOR signaling pathway

“…PTen, an important tumor suppressor gene, is one of the most commonly deleted or mutated tumor suppressors in a variety of types of human cancer, including breast (33), prostate (34), and cervical cancer (35). PTen inactivates the Pi3K/aKT/mTor signaling pathway, which is involved in an abundance of essential cellular processes, such as cell growth, differentiation, proliferation and migration; most of these processes have also been associated with cancer progression (36).…”

Identification of oxidative stress-related genes associated with immune cells in Aortic Valve Stenosis based on bioinformatics analysis

“…IGFBP-2 is reported to be a "dark horse" physiologically and pathologically. IGFBP-2 expressions have been shown to change in a variety of diseases, such as malignancies (28,29), those related to metabolism (30) immune-related diseases (31), and cardiovascular disease (32,33). Increased expression of IGFBP-2 increased intracellular hydrogen peroxide activity (34).…”

Insulin‑like growth factor axis: A potential nanotherapy target for resistant cervical cancer tumors (Review)

“…However, IGFBP-2 has also been demonstrated to interact with integrins to exert oncogenic effects that promote cell proliferation and invasion and suppress apoptosis. Specifically, studies have shown that IGFBP-2 is associated with metastasis and uses integrin-dependent mechanisms to reduce cell adhesion and promote invasion, suggesting that IGFBP-2 has IGF-independent oncogenic effects (52)(53)(54). By contrast, IGFBP-3 is known to protect against cancer via the p53-mediated activation of apoptosis.…”