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Qian Liu,1,* Yang Li,1,* Weiling Lv,2 Guangwei Zhang,1 Xin Tian,1 Xiaodong Li,1 Hepeng Cheng,1 Chaoyang Zhu1 1Department of Urology, Huaihe Hospital of Henan University, Kaifeng, Henan, 2Department of Pharmacy, Huaihe Hospital of Henan University, Kaifeng, Henan, China *These authors contributed equally to this work Background: Renal cell carcinoma (RCC) is the most common cancer in kidney malignancies. UCA1 has been identified as an oncogenic lncRNA in multiple cancers, including RCC. However, the underlying molecular mechanism of UCA1 involved in RCC progression is far from being addressed. Methods: Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) assays were used to measure expressions of UCA1, miR129, and SOX4 mRNA. Western blot assays were employed to detect SOX4 protein expression. Cell proliferation, invasion, and apoptosis were assessed by CCK-8, Matrigel invasion, and annexin–fluorescein isothiocyanate (FITC) apoptosis-detection assays, respectively. The interaction between UCA1 and miR129 was demonstrated by luciferase, RNA pull-down, and RNA-immunoprecipitation (RIP) assays. Luciferase assays were also used to explore whether UCA1 was able to act as a molecular sponge of miR129 to affect the interplay of miR129 and SOX4. Results: UCA1 expression was upregulated in RCC tissue and cells, and higher UCA1 expression was associated with advanced pathogenic status and poor prognosis of RCC patients. UCA1 knockdown suppressed proliferation and invasion and induced apoptosis in RCC cells. UCA1 inhibited miR129 expression by direct interaction in RCC cells. miR129 overexpression inhibited cell proliferation and invasion and promoted apoptosis. Moreover, miR129 downregulation abrogated UCA1 knockdown-mediated antiproliferation, anti-invasion, and proapoptosis effects in RCC cells. Furthermore, UCA1 acted as a ceRNA of miR129 to enhance target-gene SOX4 expression in RCC cells. Conclusion: UCA1 promoted cell proliferation and invasion and inhibited apoptosis by regulating SOX4 via miR129 in RCC, offering a promising therapeutic target and prognosis marker for RCC patients. Keywords: renal cell carcinoma, lncRNA, UCA1, miR129, SOX4, UCA1/miR129/SOX4 axis |
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