MiR-222 targeted PUMA to improve sensitization of UM1 cells to cisplatin.

MiR-222 targeted PUMA to improve sensitization of UM1 cells to cisplatin.
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MiR-222 靶向 PUMA 以提高 UM1 细胞对顺铂的敏感性。

DOI:
10.3390/ijms151222128
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发表时间:
2014-12-02
影响因子:
5.6
通讯作者:
Yu D
Yu D
中科院分区:
生物学2区
文献类型:
--
作者:
Jiang F;Zhao W;Zhou L;Liu Z;Li W;Yu D

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MicroRNAs已被证明在调节癌细胞的化疗敏感性方面发挥关键作用。作为致癌miRNAs(OncomiRs)的一员,miR-222已被报道在多种类型的恶性肿瘤中起致癌作用。然而,关于miR-222在口腔鳞状细胞癌(OSCC)中的具体作用却知之甚少。本研究探讨miR-222在上调P53蛋白表达、增强口腔鳞癌细胞对顺铂(CDDP)敏感性中的作用及其机制。结果表明,反义(AS)-miR-222可抑制miR-222的表达。相比之下,PUMA则显著上调。AS-miR-222联合CDDP处理的细胞IC50值显著降低,比单独CDDP处理的细胞IC50值降低的幅度更大。此外,AS-miR-222可促进UM1细胞的凋亡并抑制其侵袭力。以上数据分析表明,在UM1细胞中,miR-222和PUMA之间可能存在一个调控环,并且miR-222抑制增加了对CDDP的化疗敏感性。这些结果表明,下调miR-222可以增强人口腔鳞癌细胞对CDDP的敏感性,AS-miR-222联合CDDP可能通过上调PUMA的表达来控制口腔鳞癌的生长,是一种有效的治疗策略。
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.
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