As a prevalent tumor among women, breast cancer is still an incurable disease due to drug resistance. In this study, we report microRNA-221 to have a significant effect on breast cancer resistance to adriamycin. The microRNA-221 is elevated in tumor tissue compared with nearby nontumor samples, as well as in breast cancer cell line with adriamycin resistance (MCF-7/ADR) compared to its parental line (MCF-7) and the normal breast epithelial cell line (MCF-10A). Enforced level of microRNA-221 promotes cancer resistance to adriamycin, which in turn sustains cell survival and exacerbates malignant formation. Reciprocally, the silence of microRNA-221 in cancer cells augments the sensitivity to chemotherapy, thereby resulting in enhanced apoptosis of MCF-7/ADR cells. Mechanistically, we identify PTEN as a direct target of microRNA-221, which was conversely associated with a microRNA-221 level in breast tumors. The knock-down of PTEN partially reversed the stimulatory role of microRNA-221 in the modulation of the Akt/mTOR signaling. Taken together, these findings suggest microRNA-221 suppresses PTEN transcription and activates Akt/mTOR pathway, which in turn enhances breast cancer resistance to adriamycin and promotes cancer development. Our data thus illuminate the microRNA-221/PTEN axis may act as a promising strategy for the treatment of chemotherapy-resistant breast tumors.

中文翻译：

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MicroRNA-221通过调节PTEN / Akt / mTOR信号传导促进乳腺癌对阿霉素的耐药性。

作为女性中普遍存在的肿瘤，由于耐药性，乳腺癌仍然是无法治愈的疾病。在这项研究中，我们报道了microRNA-221对乳腺癌对阿霉素的耐药性具有显著作用。与附近的非肿瘤样本相比，microRNA-221在肿瘤组织中升高，与亲本细胞系（MCF-7）和正常的乳腺癌上皮细胞系相比，阿霉素耐药的乳腺癌细胞系（MCF-7 / ADR）升高（MCF-10A）。增强水平的microRNA-221会增强对阿霉素的抗药性，进而维持细胞存活并加剧恶性肿瘤的形成。相反，癌细胞中microRNA-221的沉默增强了对化学疗法的敏感性，从而导致MCF-7 / ADR细胞凋亡增强。从机制上讲，我们确定PTEN是microRNA-221的直接靶标，相反，这与乳腺肿瘤中的microRNA-221水平相关。PTEN的敲低部分逆转了microRNA-221在Akt / mTOR信号传导调节中的刺激作用。综上所述，这些发现表明microRNA-221抑制PTEN转录并激活Akt / mTOR途径，从而增强乳腺癌对阿霉素的抵抗力并促进癌症的发展。因此，我们的数据阐明了microRNA-221 / PTEN轴可能是治疗化疗耐药性乳腺肿瘤的有前途的策略。继而增强了乳腺癌对阿霉素的抵抗力并促进了癌症的发展。因此，我们的数据阐明了microRNA-221 / PTEN轴可能是治疗化疗耐药性乳腺肿瘤的有前途的策略。继而增强了乳腺癌对阿霉素的抵抗力并促进了癌症的发展。因此，我们的数据阐明了microRNA-221 / PTEN轴可能是治疗化疗耐药性乳腺肿瘤的有前途的策略。