Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, 01‑813 Warsaw, Poland.
Int J Mol Med. 2022 Apr;49(4). doi: 10.3892/ijmm.2022.5108. Epub 2022 Feb 18.
TGF‑β1 is a pleiotropic cytokine that can either promote or inhibit cancer development and progression. It was previously found that TGF‑β1 can regulate the expression of several microRNAs (miR or miRNA) involved in the progression of renal cell carcinoma (RCC). Therefore, the present study aimed to analyze the effects of TGF‑β1 on the global RCC miRNome. It was found that TGF‑β1 can regulate a complex network consisting of miRNAs and mRNAs involved in RCC transformation. In particular, TGF‑β1 was revealed to regulate the proliferation of RCC cells while concomitantly modifying the expression of oncogenic regulators, including avian erythroblastosis virus E26 (V‑Ets) oncogene homolog‑1 (ETS1). In addition, TGF‑β1 was demonstrated to regulate the expression of a number of miRNAs including miR‑30c‑5p, miR‑155‑5p, miR‑181a‑5p and miR‑181b‑5p. By contrast, TGF‑β1 reciprocally modified the expression of genes encoding TGF‑β1 receptors and SMADs, indicating a novel regulatory feedback mechanism mediated through the miRNAs. These data suggested that ETS1 served different roles in different subtypes of RCC tumors, specifically by functioning as an oncogene in clear cell RCC while as a tumor suppressor in papillary RCC.
TGF-β1 是一种多功能细胞因子,可以促进或抑制癌症的发展和进展。先前发现 TGF-β1 可以调节参与肾细胞癌 (RCC) 进展的几种 microRNA(miR 或 miRNA)的表达。因此,本研究旨在分析 TGF-β1 对全球 RCC miRNA 组的影响。结果发现,TGF-β1 可以调节一个由 miRNA 和 mRNAs 组成的复杂网络,这些 miRNA 和 mRNAs 参与 RCC 的转化。特别是,TGF-β1 被揭示可以调节 RCC 细胞的增殖,同时改变包括禽红细胞增多症病毒 E26(V-Ets)致癌基因同源物 1(ETS1)在内的致癌调节剂的表达。此外,TGF-β1 被证明可以调节包括 miR-30c-5p、miR-155-5p、miR-181a-5p 和 miR-181b-5p 在内的许多 miRNA 的表达。相比之下,TGF-β1 反向调节编码 TGF-β1 受体和 SMADs 的基因的表达,表明通过 miRNA 介导了一种新的调节反馈机制。这些数据表明,ETS1 在不同亚型的 RCC 肿瘤中发挥不同的作用,具体来说,在透明细胞 RCC 中作为癌基因,在乳头状 RCC 中作为肿瘤抑制基因。