Quaking I-5 protein inhibits invasion and migration of kidney renal clear cell carcinoma via inhibiting epithelial-mesenchymal transition suppression through the regulation of microRNA 200c.
Quaking I-5 protein inhibits invasion and migration of kidney renal clear cell carcinoma via inhibiting epithelial-mesenchymal transition suppression through the regulation of microRNA 200c.
复制标题
Quaking I-5蛋白通过调控microRNA 200c抑制上皮间质转化抑制肾透明细胞癌的侵袭和迁移
DOI：
10.21037/tau-21-833
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发表时间：
2021-10
影响因子：
2
通讯作者：
Bao Y
中科院分区：
文献类型：
--
作者：
Zhang R;Wang W;Aimudula A;Lu S;Lu P;Aihaiti R;Bao Y
研究表明，震颤I-5蛋白（QKI-5）在多种肿瘤的转移中起着重要作用。然而，QKI-5在肾透明细胞癌（KIRC）转移中的作用和机制尚不清楚。因此，本研究旨在探讨QKI-5在KIRC转移中的作用机制。采用实时定量逆转录聚合酶链反应（qRT-PCR）和western blot检测KIRC组织和不同细胞系中QKI-5的表达。免疫组化法检测原发灶和转移灶中QKI-5的表达。分别用创伤愈合和transwell实验检测细胞迁移和侵袭能力。免疫印迹和免疫荧光染色检测上皮间质转化标志物蛋白的表达。使用双荧光素酶报告基因测定证实QKI-5通过microRNA 200 c（miR-200 c）的相互作用。虽然QKI-5在KIRC组织中比在正常肾组织中更可能显著下调，但其在转移性KIRC肿瘤中显著升高。QKI-5的上调促进细胞迁移和侵袭，并提高上皮间质转化（EMT）标志蛋白的表达，包括波形蛋白，蜗牛和蛞蝓，而它下调E-cadherin。此外，双荧光素酶报告基因分析表明，QKI-5是miR-200 c的直接靶点，并且miR-200 c可以逆转QKI-5对细胞迁移、侵袭和EMT标志物蛋白表达的影响。我们的研究结果显示，miR-200 c下调QKI-5通过EMT过程减弱了KIRC的迁移和侵袭，表明QKI-5可能是一个潜在的治疗靶点，也是KIRC进展的关键指标。
It has been demonstrated that quaking I-5 protein (QKI-5) plays crucial roles in the metastasis of various kinds of cancers. However, the function and mechanism of QKI-5 in kidney renal clear cell carcinoma (KIRC) metastasis remains unclear. Therefore, this study aimed to explore the mechanism of QKI-5 in the metastasis of KIRC. The expression of QKI-5 was detected using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot in KIRC tissues and different cell lines. Immunohistochemical staining was used to detect the quantity of QKI-5 in primary and metastases of KIRC. Cell migration and invasion were measured using wound healing and transwell assays respectively. The quantity of epithelial mesenchymal transition marker proteins was detected using western blot and immunofluorescence staining. The interaction of QKI-5 via microRNA 200c (miR-200c) was confirmed using dual luciferase reporter assay. Although QKI-5 was significantly more likely to be downregulated in KIRC tissues than that in normal Kidney tissues, it was dramatically elevated in metastatic KIRC tumors. Upregulation of QKI-5 promoted cell migration and invasion and elevated the expression of epithelial-mesenchymal transition (EMT) marker proteins, including vimentin, snail and slug, while it was downregulated for E-cadherin. Furthermore, a dual luciferase reporter assay demonstrated that QKI-5 was a direct target of miR-200c, and that miR-200c could reverse the effect of QKI-5 on cell migration, invasion, and expression of EMT marker proteins. Our results revealed that downregulation of QKI-5 by miR-200c attenuated KIRC migration and invasion via the EMT process, indicating that QKI-5 may be a potential therapeutic target and a key indicator of KIRC progression.