MiR-222 Targeted PUMA to Improve Sensitization of UM1 Cells to CisplatinReportar como inadecuado




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Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, China



These authors contributed equally to this work.





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Abstract microRNAs have been shown to play critical roles in regulating the chemosensitivity of cancer cells. As a member of the oncogenic miRNAs oncomiRs, miR-222 has been reported to drive the oncogenesis of many types of malignancies. However, little is known concerning the specific role of miR-222 in human oral squamous cell carcinoma OSCC. The present study explored the role and mechanism of miR-222 in increasing the expression of p53 up-regulated modulator of apoptosis PUMA and enhancing the sensitivity of OSCC to cisplatin CDDP. Results showed that antisense As-miR-222 inhibits the expression of miR-222. In contrast, PUMA was dramaticallyup-regulated. IC50 values were significantly decreased in cells treated with As-miR-222 combined with CDDP, to a greater extent than in cells treated with CDDP alone. Furthermore, As-miR-222 enhanced apoptosis and inhibited the invasiveness of UM1 cells. Analysis of the above data suggested that, in UM1 cells, there might be a regulatory loop between miR-222 and PUMA, and that miR-222 inhibition increased the chemosensitivity to CDDP. These findings demonstrated that down-regulation of miR-222 could enhance the chemosensitivity of human OSCC cells to CDDP, and that the combination of As-miR-222 and CDDP could be an effective therapeutic strategy by boosting the expression of PUMA for controlling the growth of OSCC. View Full-Text

Keywords: OSCC; PUMA; miR-222; cisplatin OSCC; PUMA; miR-222; cisplatin





Autor: Fangfang Jiang †, Wei Zhao †, Lijie Zhou, Zifeng Liu, Wenqing Li and Dongsheng Yu *

Fuente: http://mdpi.com/



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