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

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.

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.

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. Conclusions: 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.