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miR-205-3p在卵巢癌中发挥肿瘤抑制作用。

miR-205-3p Functions as a Tumor Suppressor in Ovarian Carcinoma.

作者信息

Qiao Baohua, Wang Qingzhi, Zhao Yuying, Wu Jingli

机构信息

Heze Municipal Hospital, No. 28888 Caozhou Road, Heze, 274000, Shandong, China.

出版信息

Reprod Sci. 2020 Jan;27(1):380-388. doi: 10.1007/s43032-019-00047-y. Epub 2020 Jan 6.

Abstract

Ovarian cancer (OC) represents the most lethal form of gynaecologic cancers in developed countries. To develop a better therapeutic against OC, characterizing new classes of molecular regulators such as microRNAs (miRNAs) involved in OC tumorigenesis becomes immensely important. We used human OC cell lines to study the expression pattern of miRNA-205-3p. We then employed miRNA-205-3p mimic and inhibitor to elucidate its functional role in OC cells. Downstream target of miRNA-205-3p was characterized in OC cells with luciferase gene reporter assay and Western blotting. Its functional role in OC was also investigated with the siRNA approach. Lastly, we assessed the expression change of miRNA-205-3p and its newly identified target in human OC tissues. miR-205-3p was downregulated in five human OC lines tested. Over-expressing miR-205-3p reduced OC cell proliferation and migration. MAPK10 was identified as a direct target of miR-205-3p. Knocking down MAPK10 suppressed OC cell growth and migration. In contrast, knocking down miR-205-3p promoted clonogenicity of primary ovary cells. In clinical samples, miR-205-3p and MAPK10 expressed inversely in accordance with their expression patterns in OC cells. miR-205-3p was shown as a novel tumor suppressor in OC via inhibiting the MAPK10 pathway. This new finding may inspire new personalized treatment for OC.

摘要

在发达国家,卵巢癌(OC)是最致命的妇科癌症形式。为了开发更好的OC治疗方法,表征参与OC肿瘤发生的新型分子调节因子(如微小RNA(miRNA))变得极为重要。我们使用人OC细胞系研究miRNA-205-3p的表达模式。然后我们使用miRNA-205-3p模拟物和抑制剂来阐明其在OC细胞中的功能作用。通过荧光素酶基因报告测定法和蛋白质印迹法在OC细胞中表征miRNA-205-3p的下游靶标。还使用siRNA方法研究了其在OC中的功能作用。最后,我们评估了miRNA-205-3p及其新鉴定的靶标在人OC组织中的表达变化。在所测试的五个人OC细胞系中,miR-205-3p表达下调。过表达miR-205-3p可降低OC细胞的增殖和迁移。MAPK10被鉴定为miR-205-3p的直接靶标。敲低MAPK10可抑制OC细胞的生长和迁移。相反,敲低miR-205-3p可促进原代卵巢细胞的克隆形成能力。在临床样本中,miR-205-3p和MAPK10的表达与其在OC细胞中的表达模式相反。通过抑制MAPK10途径,miR-205-3p在OC中被证明是一种新型肿瘤抑制因子。这一新发现可能会激发针对OC的新的个性化治疗。

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