Downregulation of CD147 induces malignant melanoma cell apoptosis via the regulation of IGFBP2 expression.
Downregulation of CD147 induces malignant melanoma cell apoptosis via the regulation of IGFBP2 expression.
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CD147下调通过调节IGFBP2表达诱导恶性黑色素瘤细胞凋亡
DOI：
10.3892/ijo.2018.4579
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发表时间：
2018-12
影响因子：
5.2
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Zhao S;Wu L;Kuang Y;Su J;Luo Z;Wang Y;Li J;Zhang J;Chen W;Li F;He Y;Tao J;Zhou J;Xu X;Peng C;Chen X
分化簇(CD)147作为一种跨膜糖蛋白，在多种肿瘤中均有高表达。越来越多的证据表明，CD147在肿瘤细胞的死亡和存活中起着关键作用，但其潜在的机制还需要进一步的研究。本研究发现，CD147基因敲除可显著增加黑色素瘤细胞的凋亡率。此外，CD147的下调逆转了黑色素瘤的恶性表型，正如在异种移植小鼠模型中诱导肿瘤细胞凋亡所证明的那样。此外，利用人细胞凋亡抗体芯片鉴定了9个与CD147相关的差异表达的凋亡相关蛋白，包括胰岛素样生长因子结合蛋白2(IGFBP2)。此外，观察到CD147基因敲除显著降低了黑色素瘤细胞IGFBP2在mRNA和蛋白水平的表达。鉴于IGFBP2是磷酸酶和紧张素同源蛋白(PTEN)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)信号通路的下游分子，我们研究了CD147对这一信号通路的影响。有趣的是，在CD147低表达的黑色素瘤细胞中，雷帕霉素的磷酸化(P)-AKT和p-机械靶标的表达减弱，而PTEN的表达显著上调。此外，PI3K特异性抑制剂的应用也降低了IGFBP2的表达。重要的是，与对照组相比，IGFBP2在黑色素瘤的临床组织中高表达，并且其表达与CD147呈正相关。本研究发现CD147通过IGFBP2和PTEN/PI3K/AKT信号通路在黑色素瘤细胞的凋亡过程中发挥重要作用。临床黑色素瘤组织中有IGFBP2和CD147的高表达，IGFBP2与CD147的表达呈正相关，提示CD147可能是黑色素瘤化疗或预防的潜在治疗靶点。
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.
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影响因子：
9.7
作者：
Kuang, Ye-Hong;Chen, Xiang;Kanekura, Takuro
通讯作者：
Kanekura, Takuro
影响因子：
6.2
作者：
Bhattacharya K;Maiti S;Mandal C
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Mandal C
影响因子：
8
作者：
Dong, Y.;Richards, J-A E.;Wajapeyee, N.
通讯作者：
Wajapeyee, N.
影响因子：
3.9
作者：
Biernacka, K. M.;Uzoh, C. C.;Holly, J. M. P.
通讯作者：
Holly, J. M. P.
影响因子：
5.7
作者：
Li, Qing-Quan;Wang, Wen-Juan;Xu, Zu-De
通讯作者：
Xu, Zu-De