Overexpression of microRNA-21 decreased the sensitivity of advanced cervical cancer to chemoradiotherapy through SMAD7

赫拉 小RNA 宫颈癌 转染 免疫印迹 癌症研究 放化疗 下调和上调 医学 癌症 上皮-间质转换 抗药性 肿瘤科 癌细胞 污渍 细胞 细胞培养 内科学 生物 转移 基因 微生物学 生物化学 遗传学
作者
Qifang Liu,Shuang Liu,Danbo Wang
出处
期刊:Anti-Cancer Drugs [Lippincott Williams & Wilkins]
卷期号:31 (3): 272-281 被引量:10
标识
DOI:10.1097/cad.0000000000000871
摘要

Drug resistance is a major problem in the treatment of advanced cervical cancer. The oncogenic microRNA-21 (miR-21) is involved in drug resistance in various cancers. However, the regulatory role of miR-21 and its target, Smad7 in drug resistance of cervical cancer remains to be elucidated. We compared miR-21 and Smad7 levels in human samples from chemoradiotherapy-resistance cervical cancer (resistant group) and chemoradiotherapy-sensitive cervical cancer (sensitive group) patients. Then, the miR-21 level was manipulated in HeLa and SiHa cervical cancer cells and the Smad7 level was determined by PCR and western blot. We also manipulated miR-21, Smad7 or both in cells, and measured cell viability using cell counting kit-8 method and epithelial–mesenchymal transition (EMT) biomarkers using Western blot. In human samples, resistant group has significantly higher miR-21 and lower Smad7 levels than sensitive group. In-vitro analysis demonstrated downregulated Smad7 after transfection with miR-21 mimics. When cells were transfected with Smad7 inhibitor, we observed increased drug resistance and changed levels of EMT-biomarkers after chemoradiotherapy, suggesting that downregulation of Smad7 decreased the sensitivity through EMT. When the cells were transfected with miR-21 inhibitor alone, we found increased sensitivity to chemoradiotherapy through EMT. However, such effects were attenuated when Smad7 was also downregulated after cotransfection. In summary, we provided clinical and experimental evidence that decreased miR-21 may improve drug resistance through EMT by direct targeting Smad7 in cervical cancer. Our data suggest that miR-21/Smad7 pathway may be an effective target for drug resistance in cervical cancer treatment.

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