TRPM7 Regulates AKT/FOXO1–Dependent Tumor Growth and Is an Independent Prognostic Indicator in Renal Cell Carcinoma

Abstract

Transient receptor potential melastatin 7 (TRPM7) is important for the tumorigenesis and progression of several cancers. However, little is known about TRPM7 expression and its clinical significance in clear cell renal cell carcinoma (ccRCC). The expression dynamics of TRPM7 was examined in a clinical cohort of RCC specimens by qPCR, immunoblotting, and IHC staining. A series of and assays were performed to elucidate the function of TRPM7 in RCC and the underlying mechanisms. For the first time, results demonstrate that TRPM7 expression is markedly higher in RCC cell lines and clinical samples and had a positive correlation with T status, tumor size, and poor patients' overall survival and progression-free survival. Preclinical studies using multiple RCC cells and a mouse model indicate that TRPM7 promotes cell proliferation and colony formation and tumor growth Mechanistically, TRPM7 promotes AKT phosphorylation, leading to repression of the FOXO1 expression and transcriptional activity. Moreover, luciferase reporter assays demonstrate that miR-129-3p directly targets the 3'-UTR of TRPM7 and acts as a negative regulator of TRPM7. These findings reveal an important role for TRPM7 in the regulation of RCC growth and represent a novel prognostic biomarker for this disease. TRPM7 is an independent prognostic indicator in RCC, and targeting the TRPM7 signaling pathway may be a novel therapeutic approach for the treatment of RCC. .

MiR‐9 promotes angiogenesis of endothelial progenitor cell to facilitate thrombi recanalization via targeting TRPM7 through PI3K/Akt/autophagy pathway

“…In the present study, TRPM7 was identified as the target gene of miR‐9‐5p via luciferase assay. Accumulating evidence indicates that TRPM7 is essential for multiple cellular processes, including survival, proliferation and migration in stem cells and endothelial cells via PI3K/Akt pathways . It has been well demonstrated that TRPM7 could inhibit the growth and migration of human umbilical vein endothelial cells (HUVECs) .…”

Molecular Mechanisms in Clear Cell Renal Cell Carcinoma: Role of miRNAs and Hypermethylated miRNA Genes in Crucial Oncogenic Pathways and Processes

“…The tumor suppressor and anti-metastatic functions of the hypermethylated MIR-129-2 gene we discovered (Beresneva et al, 2013), are consistent with the data that miR-129-3p downregulates multiple metastasis-related genes in RCC cells, including SOX4 , and also decreased phosphorylation of focal adhesion kinase and expression of MMP-2/9 (Chen et al, 2014). In addition, miR-129-3p is involved in miR-129-3p/TRPM7/AKT/FOXO1 signaling pathway (Zhao Z. et al, 2018). The collective data confirm the ability of miR-129-3p to restrain metastasis in ccRCC.…”

Prognostic Value of TRPM7 Expression and Factor XIIIa-Expressing Tumor-Associated Macrophages in Gastric Cancer

“…The expression of TRPM7 in GC was assessed using the IHC scoring method confirmed in previous studies [ 23 , 24 ]. During evaluation process, cytoplasmic and membranous staining in tumor cells were taken into consideration.…”