MicroRNA-221 targets PTEN to reduce the sensitivity of cervical cancer cells to gefitinib through the PI3K/Akt signaling pathway
MicroRNA-221 targets PTEN to reduce the sensitivity of cervical cancer cells to gefitinib through the PI3K/Akt signaling pathway
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DOI：
10.1007/s13277-015-4247-8
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发表时间：
2016-03-01
期刊：
影响因子：
--
通讯作者：
Zhang, ZongFeng
中科院分区：
文献类型：
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作者：
Du, Juan;Wang, LiNa;Zhang, ZongFeng
宫颈癌患者对酪氨酸激酶抑制剂吉非替尼（gefitinib）的临床反应最小，吉非替尼靶向表皮生长因子受体（EGFR）。对吉非替尼敏感的分子机制尚不清楚。本研究的目的是探讨microRNA-221（miR-221）影响吉非替尼敏感性的可能机制。我们发现，与邻近正常组织相比，宫颈癌组织中miR-221的表达显着增加。宫颈癌细胞中miR-221表达上调降低了PTEN表达水平，导致pAkt和BCL-2表达增加。重要的是，吉非替尼的敏感性通过miR-221的上调而降低，这被pcDNA-PTEN共转染或磷脂酰肌醇-3激酶（PI 3 K）抑制剂LY 294002阻断。这些数据表明，miR-221可以通过PTEN/PI 3 K/Akt信号通路降低宫颈癌细胞对吉非替尼的敏感性。miR-221是增加宫颈癌治疗中吉非替尼敏感性的潜在靶点。
Patients with cervical cancer show minimal clinical response to the tyrosine kinase inhibitor gefitinib, which targets the epidermal growth factor receptor (EGFR). The molecular mechanisms underlying sensitivity to gefitinib are unknown. The purpose of this study was to investigate the possible mechanism by which microRNA-221 (miR-221) affects sensitivity to gefitinib. We showed that miR-221 expression was significantly increased in cervical cancer tissues compared with adjacent normal tissues. Upregulation of miR-221 expression in cervical cancer cells decreased PTEN expression levels, resulting in increased pAkt and BCL-2 expression. Importantly, gefitinib sensitivity was decreased by the upregulation of miR-221, which was blocked by pcDNA-PTEN co-transfection or by the phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002. These data suggest that miR-221 can reduce the sensitivity of cervical cancer cells to gefitinib through the PTEN/PI3K/Akt signaling pathway. miR-221 represents a potential target to increase the sensitivity to gefitinib in cervical cancer treatment.