Abstract

Circular RNAs (circRNAs) monitor the development of clear cell renal cell carcinoma (ccRCC). However, the role of CircPUM1 in ccRCC malignancy is not studied. We estimated the mechanism of CircPUM1 in ccRCC progression in this study. CircPUM1 expression in ccRCC tissues and cells was detected. The expression of CircPUM1 was interfered in ccRCC cells, and its effects on the growth of ccRCC cells were studied. Nuclear/cytosol fractionation assay was performed for the location of CircPUM1, and the downstream miR, gene, and pathway involved in ccRCC progression were explored through gain- and loss-of-function experiments. CircPUM1 was highly expressed in ccRCC samples and cells. Inhibition of CircPUM1 prevented the growth ccRCC cells. CircPUM1 was localized in the cytoplasm and bound to miR-340-5p. Overexpression of miR-340-5p inhibited the growth of ccRCC cells. miR-340-5p targeted FABP7, and CircPUM1 induced FABP7 expression and the activation of MEK/ERK pathway through competitively binding to miR-340-5p. Overexpression of FABP7 attenuated the inhibitory effect of CircPUM1 silencing on the growth of ccRCC cells. Overall, CircPUM1 upregulates FABP7 expression by competitively binding to miR-340-5p, and then activates the MEK/ERK pathway, thus promoting ccRCC progression.

摘要

环状 RNA (circRNA) 监测透明细胞肾细胞癌 (ccRCC) 的发展。然而，尚未研究 CircPUM1 在 ccRCC 恶性肿瘤中的作用。我们在本研究中估计了 CircPUM1 在 ccRCC 进展中的机制。检测了ccRCC组织和细胞中CircPUM1的表达。CircPUM1在ccRCC细胞中的表达受到干扰，并对其对ccRCC细胞生长的影响进行了研究。对 CircPUM1 的位置进行了核/胞质溶胶分离测定，并通过功能获得和功能丧失实验探索了参与 ccRCC 进展的下游 miR、基因和途径。CircPUM1 在 ccRCC 样本和细胞中高度表达。CircPUM1 的抑制阻止了 ccRCC 细胞的生长。CircPUM1 定位于细胞质并与 miR-340-5p 结合。miR-340-5p的过表达抑制了ccRCC细胞的生长。miR-340-5p 靶向 FABP7，CircPUM1 通过竞争性结合 miR-340-5p 诱导 FABP7 表达和 MEK/ERK 通路的激活。FABP7 的过表达减弱了 CircPUM1 沉默对 ccRCC 细胞生长的抑制作用。总体而言，CircPUM1 通过竞争性结合 miR-340-5p 上调 FABP7 表达，然后激活 MEK/ERK 通路，从而促进 ccRCC 进展。