TGF‑β1 affects the renal cancer miRNome and regulates tumor cells proliferation

Abstract

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.

Renal clear cancer cells regulate the differentiation of urine‐derived stem cells to carcinoma‐associated fibroblasts via RUNX3/TGF‐β1 signaling axis

“…Previous studies indicated that TGF‐β1 played a crucial role in the transformation of MSCs to CAFs in various cancers (Xiong et al, 2020). In a case, it was reported that the TGF‐β1 signaling pathway was abnormally activated in the ccRCC cells (Hanusek et al, 2022). Similarly, our analysis of KIRC data in the TCGA database indicated that the TGF‐β1 expression level was significantly higher in the KIRC tumor tissues than in the paracancerous tissues (Figure 2a).…”

A Four-MicroRNA Panel in Serum as a Potential Biomarker for Screening Renal Cell Carcinoma

“…Also, miR-181b-5p encapsulated in tumor-derived extracellular vesicles could affect angiogenesis to promote the tumorigenesis and metastasis of esophageal squamous cell carcinoma (Wang et al, 2020). In the study of RCC, TGF-β1 affected the expression of miR-181b-5p to regulate the proliferation and progression of RCC (Hanusek et al, 2022). Also, miR-181b-5p was upregulated by circular RNA circCSNK1G3 to promote tumor growth and metastasis in RCC via the TIMP3-mediated epithelial-to-mesenchymal transition (EMT) process (Li et al, 2021).…”

Coordinated reprogramming of renal cancer transcriptome, metabolome and secretome associates with immune tumor infiltration

“…Reverse transcription and qPCR were performed as described previously [ 10 ]. The sequences of the primers used in the study are presented in Additional file 1 : Table S2.…”