Downregulation of CD147 induces malignant melanoma cell apoptosis via the regulation of IGFBP2 expression

Abstract

Cluster of differentiation (CD)147, as a transmembrane glycoprotein, is highly expressed in a variety of tumors. Accumulating evidence has demonstrated that CD147 serves critical roles in tumor cell death and survival; however, the underlying mechanism requires further investigation. In the present study, it was revealed that CD147 knockdown significantly increased melanoma cell apoptosis. In addition, downregulation of CD147 reversed the malignant phenotype of melanoma, as demonstrated by the induction of tumor cell apoptosis in a xenograft mouse model. In addition, a human apoptosis antibody array was performed and 9 differentially expressed apoptosis-related proteins associated with CD147 were identified, including insulin-like growth factor-binding protein 2 (IGFBP2). Additionally, CD147 knockdown was observed to significantly decreased IGFBP2 expression at the mRNA and protein levels in melanoma cells. Providing that IGFBP2 is a downstream molecule in the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, the effects of CD147 on this particular pathway were investigated. Interestingly, the expression of phosphorylated (p)-AKT and p-mechanistic target of rapamycin was attenuated, whereas PTEN was markedly upregulated in CD147-underexpressing melanoma cells. Furthermore, application of a PI3K-specific inhibitor also decreased IGFBP2 expression. Importantly, IGFBP2 was highly expressed in clinical tissues of melanoma compared with the control group, and its expression exhibited a positive association with CD147. The present study revealed that CD147 served a critical role in mediating the apoptosis of melanoma cells via IGFBP2 and the PTEN/PI3K/AKT signaling pathway. IGFBP2 and CD147 were observed to be overexpressed in clinical melanoma tissues; IGFBP2 was shown to be positively associated with CD147 expression, suggesting that CD147 may be considered as a potential therapeutic target for chemotherapy or prevention for in melanoma.

High expression level of peptidylprolyl isomerase A is correlated with poor prognosis of liver hepatocellular carcinoma

“…Studies by Lu et al (53) and de la Iglesia et al (54) demonstrated that BSG overexpression was highly associated with poor prognosis of lung adenocarcinoma and breast cancer by stimulating the production of matrix metalloproteinases. Zhao et al (55) demonstrated that downregulation of BSG induced malignant melanoma cell apoptosis via the regulation of IGFBP2 expression. Lu et al (53) revealed that basolateral CD147 induced hepatocyte polarity loss by E-cadherin ubiquitination and degradation in the progression of hepatocellular carcinoma.…”

Anticancer properties of dried-pericarp water extracts of Camellia japonica L. fermented with Aspergillus oryzae through regulation of IGFBP-2/mTOR pathway

“…Increase in the expression of IGFBP-2 in lung cancer cells 39 , breast cancer cells 42 , and cervical cancer cells 43 increased the proliferation of cells. Conversely, decrease in the expression of IGFBP-2 in skin cancer cells 44 and colorectal cancer cells 45 decreased the proliferation of cells. In these cancer cells, IGFBP-2 acts as an oncogene, and the decrease in cell viability by AOFE treatment may be attributed to the possibility that the expression of IGFBP-2 may be regulated by AOFE treatment.…”

Large-Scale Single-Cell and Bulk Sequencing Analyses Reveal the Prognostic Value and Immune Aspects of CD147 in Pan-Cancer

“…Moreover, CD147 acts as a key role in mediating tumor cell invasiveness via regulating MMP expression, such as MMP-2 and MMP-9 in adjacent cancer cells or CAFs ( 25 , 26 ). One study indicated that CD147 could induce malignant melanoma cell apoptosis through IGFBP2 and PTEN/PI3K/AKT signaling pathway ( 27 ). In a HNSCC xenograft model, Binbin Yu et al.…”