Over-Expressed miR-224 Promotes the Progression of Cervical Cancer via Targeting RASSF8.
Over-Expressed miR-224 Promotes the Progression of Cervical Cancer via Targeting RASSF8.
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过度表达的 miR-224 通过靶向 RASSF8 促进宫颈癌的进展
DOI：
10.1371/journal.pone.0162378
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Cheng X
中科院分区：
文献类型：
--
作者：
Huang Y;Li Y;Wang FF;Lv W;Xie X;Cheng X
宫颈癌是发展中国家女性癌症相关死亡的最常见原因。识别新的预后预测因子或治疗靶点可以改善患者的预后。在本研究中，我们通过实时PCR证明，与正常宫颈组织（n = 64）相比，宫颈癌组织（n = 126）中miR-224的表达显着上调（1.82倍，P = 0.0025）。 miR-224的高表达与较差的预后因素显着相关，包括晚期FIGO分期、淋巴结转移、较大的肿瘤尺寸、血管受累和深部间质侵犯（所有P < 0.05）。 miR-224 的强制表达促进 SiHa 和 CaSki 癌细胞系的细胞增殖、迁移和侵袭。生物信息学分析表明 RASSF8（RAS 关联域家族 8）是 miR-224 的潜在靶标。蛋白质印迹分析和荧光素酶报告基因测定显示，过表达的 miR-224 分别抑制 RASSF8 蛋白表达并降低含有 RASSF8 3' 非翻译区 (UTR) 的荧光素酶报告基因的活性。此外，通过特异性 RNAi 敲除 RASSF8 在转染 miR-224 模拟物的宫颈癌细胞中显示出类似的效果。我们的研究结果表明，miR-224 直接靶向 RASSF8，从而在宫颈癌进展中充当肿瘤促进剂。
Cervical cancer is the most common cause of cancer-related deaths in women from developing countries. Identification of novel prognostic predictors or therapeutic targets may improve patient prognosis. In the current study, we demonstrated by real-time PCR that miR-224 expression was significantly upregulated (1.82-fold, P = 0.0025) in cervical cancer tissues (n = 126) compared with in normal cervical tissues (n = 64). Higher expression of miR-224 was significantly associated with poorer prognostic factors, including advanced FIGO stage, nodal metastasis, larger tumor size, vascular involvement and deep stromal invasion (all P < 0.05). Enforced expression of miR-224 promoted cell proliferation, migration and invasion in SiHa and CaSki cancer cell lines. Bioinformatic analysis indicated that RASSF8 (RAS-association domain family 8) was a potential target of miR-224. Western blot analysis and luciferase reporter assay showed that overexpressed miR-224 inhibited RASSF8 protein expression and decreased the activity of a luciferase reporter containing the 3′ untranslated region (UTR) of RASSF8, respectively. Further, RASSF8 knockdown by specific RNAi showed similar effects in cervical cancer cells transfected with miR-224 mimic. Our findings suggest that miR-224 directly targets RASSF8 and thereby acts as a tumor promoter in cervical cancer progression.
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影响因子：
--
作者：
Cui R;Kim T;Fassan M;Meng W;Sun HL;Jeon YJ;Vicentini C;Tili E;Peng Y;Scarpa A;Liang G;Zhang YK;Chakravarti A;Croce CM
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Croce CM
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Scorilas, Andreas
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10.5
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ARASU, P;WIGHTMAN, B;RUVKUN, G
通讯作者：
RUVKUN, G
影响因子：
5.3
作者：
Falvella, F. Stefania;Spinola, Monica;Dragani, Tommaso A.
通讯作者：
Dragani, Tommaso A.