Small ribosomal protein subunit S7 suppresses ovarian tumorigenesis through regulation of the PI3K/AKT and MAPK pathways.

Small ribosomal protein subunit S7 suppresses ovarian tumorigenesis through regulation of the PI3K/AKT and MAPK pathways.
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小核糖体蛋白亚基 S7 通过调节 PI3K/AKT 和 MAPK 通路抑制卵巢肿瘤发生

DOI:
10.1371/journal.pone.0079117
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Yang G
Yang G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang Z;Hou J;Lu L;Qi Z;Sun J;Gao W;Meng J;Wang Y;Sun H;Gu H;Xin Y;Guo X;Yang G

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小核糖体蛋白亚基S7 (RPS7)已被报道与多种恶性肿瘤相关,但RPS7在卵巢癌中的作用尚不清楚。在本研究中,我们发现通过特定shRNA沉默RPS7可促进卵巢癌细胞增殖,加速细胞周期进程,并略微降低细胞凋亡和对顺铂治疗的反应。RPS7的下调导致P85α、P110α和AKT2的表达增加。虽然ERK1/2、MEK1/2和P38的基础水平在卵巢癌细胞中不一致地改变,但在RPS7沉默后,MEK1/2 (Ser217/221)、ERK1/2 (Thr202/Tyr204)、JNK1/2 (Thr183/Tyr185)和P38 (Thr180/Tyr182)的磷酸化形式一致降低。RPS7缺失后,细胞的体外非锚定集落形成和体内动物肿瘤形成能力均增强。我们还发现RPS7的沉默增强了卵巢癌细胞的迁移和侵袭。综上所述,我们的结果表明RPS7通过PI3K/AKT和MAPK信号通路抑制卵巢肿瘤的发生和转移。因此,RPS7可能作为卵巢癌诊断和治疗的潜在标志物。
Small ribosomal protein subunit S7 (RPS7) has been reported to be associated with various malignancies, but the role of RPS7 in ovarian cancer remains unclear. In this study, we found that silencing of RPS7 by a specific shRNA promoted ovarian cancer cell proliferation, accelerated cell cycle progression, and slightly reduced cell apoptosis and response to cisplatin treatment. Knockdown of RPS7 resulted in increased expression of P85α, P110α, and AKT2. Although the basal levels of ERK1/2, MEK1/2, and P38 were inconsistently altered in ovarian cancer cells, the phosphorylated forms of MEK1/2 (Ser217/221), ERK1/2 (Thr202/Tyr204), JNK1/2 (Thr183/Tyr185), and P38 (Thr180/Tyr182) were consistently reduced after RPS7 was silenced. Both the in vitro anchorage-independent colony formation and in vivo animal tumor formation capability of cells were enhanced after RPS7 was depleted. We also showed that silencing of RPS7 enhanced ovarian cancer cell migration and invasion. In sum, our results suggest that RPS7 suppresses ovarian tumorigenesis and metastasis through PI3K/AKT and MAPK signal pathways. Thus, RPS7 may be used as a potential marker for diagnosis and treatment of ovarian cancer.
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