Department of Urology, Tangshan Central Hospital, Tangshan, China.
Department of Health Management, Tangshan Central Hospital, Tangshan, China.
Urol Int. 2022;106(11):1185-1194. doi: 10.1159/000515981. Epub 2021 Aug 17.
A number of studies reported that miR-224-5p is involved in a variety of cancer-related cellular processes, yet its physiological role in clear cell renal cell carcinoma (ccRCC) remains unclear. In order to clarify the function of miR-224-5p in ccRCC, real-time quantitative-PCR was conducted to compare the expression of miR-224-5p in human normal renal tubular epithelial cell lines and ccRCC cell lines first, and a strikingly upregulated expression was observed in ccRCC cell lines. Inhibition of miR-224-5p expression by microRNA inhibitors could inhibit the proliferation, migration, and invasion of ccRCC cells. Besides, it was validated by dual-luciferase assay in which miR-224-5p directly targeted OCLN gene. The expression of OCLN was downregulated in ccRCC cells, and overexpression of miR-224-5p could inhibit the mRNA and protein expression levels of OCLN. Overexpression of OCLN could reduce the proliferation, migration, and invasion of ccRCC cells, while overexpressed miR-224-5p could partially reverse that inhibitory effect. Therefore, the promotive effect of miR-224-5p on the proliferation, invasion, and migration of ccRCC cell lines was at least partly due to the inhibition of OCLN expression. These findings highlighted the important function of miR-224-5p, which was promoting cell proliferation, migration, and invasion by downregulating OCLN, in the pathogenesis of ccRCC, and provided a potential treatment strategy.
许多研究报道 miR-224-5p 参与了多种与癌症相关的细胞过程，但它在透明细胞肾细胞癌（ccRCC）中的生理作用尚不清楚。为了阐明 miR-224-5p 在 ccRCC 中的功能，首先通过实时定量 PCR 比较了 miR-224-5p 在人正常肾小管上皮细胞系和 ccRCC 细胞系中的表达，结果发现在 ccRCC 细胞系中表达显著上调。通过 microRNA 抑制剂抑制 miR-224-5p 的表达可以抑制 ccRCC 细胞的增殖、迁移和侵袭。此外，双荧光素酶报告基因实验验证了 miR-224-5p 可以直接靶向 OCLN 基因。在 ccRCC 细胞中 OCLN 的表达下调，过表达 miR-224-5p 可以抑制 OCLN 的 mRNA 和蛋白表达水平。过表达 OCLN 可以降低 ccRCC 细胞的增殖、迁移和侵袭能力，而过表达 miR-224-5p 可以部分逆转这种抑制作用。因此，miR-224-5p 对 ccRCC 细胞系增殖、侵袭和迁移的促进作用至少部分是由于 OCLN 表达的抑制。这些发现强调了 miR-224-5p 的重要功能，它通过下调 OCLN 促进细胞增殖、迁移和侵袭，在 ccRCC 的发病机制中发挥重要作用，并为提供了一种潜在的治疗策略。
