Anti-tumor roles of both strands of the miR-455 duplex: their targets SKA1 and SKA3 are involved in the pathogenesis of renal cell carcinoma
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Yasutaka Yamada1,2, Takayuki Arai1,2, Satoko Kojima3, Sho Sugawara1,2, Mayuko Kato1,2, Atsushi Okato1,2, Kazuto Yamazaki4, Yukio Naya3, Tomohiko Ichikawa2 and Naohiko Seki1
1Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan
2Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan
3Department of Urology, Teikyo University Chiba Medical Center, Ichihara, Japan
4Department of Pathology, Teikyo University Chiba Medical Center, Ichihara, Japan
Naohiko Seki, email: [email protected]
Keywords: microRNA; miR-455; anti-tumor; renal cell carcinoma; SKA
Received: March 02, 2018 Accepted: April 28, 2018 Published: June 01, 2018
Recent studies revealed that some passenger strands of miRNAs acted as anti-tumor or oncogenic miRNAs in cancer cells. In this study, we focused on miR-455-5p (the passenger strand) and miR-455-3p (the guide strand) based on microRNA (miRNA) expression signatures of cancer cells. Both miR-455-5p and miR-455-3p were downregulated in renal cell carcinoma (RCC) tissues and low expression of these miRNAs was significantly associated with poor prognosis. Cancer cell proliferation, migration and invasive abilities were significantly inhibited by ectopic expression of miR-455-5p and miR-455-3p. To identify their oncogenic targets, we applied a combination of genome-wide gene expression and in silico miRNA database analyses. We focused on spindle and kinetochore-associated proteins, SKA1 and SKA3 and demonstrated direct regulation of SKA1 by miR-455-5p and SKA3 by miR-455-3p in RCC cells. Our present data demonstrated overexpression of SKA3 in RCC clinical specimens. Moreover, the study showed that the miR-455-3p/SKA3 axis contributed to cancer cell aggressiveness. Analytic strategies based on anti-tumor miRNAs, including passenger strands of miRNAs, are effective approaches for the elucidation of the molecular pathogenesis of RCC.
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