MiR-193a-5p/ERBB2 act as concurrent chemoradiation therapy response indicator of esophageal squamous cell carcinoma.
MiR-193a-5p/ERBB2 act as concurrent chemoradiation therapy response indicator of esophageal squamous cell carcinoma.
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DOI：
10.18632/oncotarget.9444
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发表时间：
2016-06-28
期刊：
影响因子：
--
通讯作者：
Lu PJ
中科院分区：
文献类型：
--
作者：
Lin CH;Tsai CH;Yeh CT;Liang JL;Hung WC;Lin FC;Chang WL;Li HY;Yao YC;Hsu TI;Lee YC;Wang YC;Sheu BS;Lai WW;Calkins MJ;Hsiao M;Lu PJ
同步放化疗（CCRT）是食管癌的主要治疗方法，然而，治疗抵抗和肿瘤复发是非常常见的。升高的ERBB 2/Her 2可能至少部分导致高复发率和对CCRT的耐药。这种受体酪氨酸激酶在10-20%的食管鳞状细胞癌（ESCC）组织中上调，ERBB 2的扩增与食管癌的不良预后相关。来自131名ESCC患者的组织，沿着该疾病的细胞和动物模型被用于探测ERBB 2上调发生并导致ESCC中的负面结果的潜在机制。我们发现ERBB 2过表达抑制体外放射敏感性。此外，miR-193 a-5 p通过直接靶向3′UTR降低ERBB 2表达。增加miR-193 a-5 p增强放射敏感性并抑制体外和体内肿瘤发生。此外，miR-193 a-5 p低表达与ESCC患者的不良预后相关，CCRT反应良好的ESCC患者表现出较高的miR-193 a-5 p表达。我们的数据表明，高miR-193 a-5 p表达的患者可能会从单独的CCRT治疗中获益，然而，CCRT与赫赛汀联合治疗可能对低miR-193 a-5 p表达的患者有益。
Concurrent chemoradiation therapy (CCRT) is the predominant treatment in esophageal cancer, however resistance to therapy and tumor recurrence are exceedingly common. Elevated ERBB2/Her2 may be at least partially responsible for both the high rates of recurrence and resistance to CCRT. This receptor tyrosine kinase is upregulated in 10–20% of esophageal squamous cell carcinoma (ESCC) tissues, and amplification of ERBB2 has been correlated with poor prognosis in esophageal cancer. Tissues from 131 ESCC patients, along with cell and animal models of the disease were used to probe the underlying mechanisms by which ERBB2 upregulation occurs and causes negative outcomes in ESCC. We found that overexpression of ERBB2 inhibited radiosensitivity in vitro. Furthermore, miR-193a-5p reduced ERBB2 expression by directly targeting the 3′UTR. Increased miR-193a-5p enhanced radiosensitivity and inhibited tumorigenesis in vitro and in vivo. Additionally, low miR-193a-5p expression correlated with poor prognosis in ESCC patients, and ESCC patients with good CCRT response exhibited higher miR-193a-5p expression. Our data suggest that patients with high miR-193a-5p will likely benefit from CCRT treatment alone, however a combination of CCRT with Herceptin may be beneficial for patients with low miR-193a-5p expression.
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影响因子：
64.8
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Golub, TR
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通讯作者：
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