MicroRNA‑218 inhibits tumor angiogenesis of human renal cell carcinoma by targeting GAB2

Abstract

Renal cell carcinoma (RCC) is one of the most common malignant cancers in the adult urinary system worldwide. Tumor angiogenesis is a critical process during cancer progression, as it modulates carcinogenesis and metastasis. In recent years, microRNA-218 (miR-218) has been confirmed to play a crucial role in tumor suppression. However, the role of miR-218 in RCC angiogenesis remains unclear. In the present study, it was found that the expression of miR-218 was decreased in RCC tumor tissues and cell lines as detected by real-time PCR analysis. Tube formation assays and migration assays also confirmed that miR-218 inhibited the interaction between RCC cells and vascular endothelial cells by suppressing proangiogenic factor vascular endothelial growth factor A (VEGFA) in RCC cells. miR-218 also repressed the subcutaneous tumorigenesis of RCC cells in nude mice, and the corneal angiogenesis in rabbit eyes. The underlying molecular mechanism was elucidated; miR-218 targets GRB2-associated binding protein 2 (GAB2), thereby inhibiting the PI3K/AKT/mTOR/VEGFA pathway. These results provide new insights into the mechanism of RCC carcinogenesis and progression, suggesting that miRNA-218 may be a therapeutic target for the treatment of RCC.

Cuproptosis-related gene FDX1 as a prognostic biomarker for kidney renal clear cell carcinoma correlates with immune checkpoints and immune cell infiltration

“…As the main pathological type of RCC, KIRC accounts for more than 80% of RCC ( Alsaab et al, 2018 ). Advanced patients with KIRC are not sensitive to radiotherapy and chemotherapy, and miss the opportunity of surgery because of metastasis ( Mu et al, 2020 ). Targeted therapy can benefit some patients, however, many advanced patients are ineffective to the existing targeted drug ( Li et al, 2018 ).…”

Role of microRNA‑218‑5p in sevoflurane‑induced protective effects in hepatic ischemia/reperfusion injury mice by regulating GAB2/PI3K/AKT pathway

“…In the present study, GAB2 was identified as a direct target of miR-218-5p, which is consisted with a previous report ( 36 ). It is well reported that miR-218 inhibited the tumor angiogenesis in human cancer via regulating the GAB2/PI3K/AKT signaling pathway in various cancer types ( 36 , 56 ). Thus, it was speculated that Sevo may have protective effects on HIRI via modulating the GAB2/AKT/mTOR signaling pathway by increasing miR-218-5p expression.…”

BATF Inhibits Cell Proliferation and Migration via PI3K/AKT/mTOR Pathway in Clear Cell Renal Cell Carcinoma

“…Such as, BATF is found to interact with JUNB to form heterodimer and then forms a complex with IRF4 in immune cells. After binding the AICE sequence (5'-TGAnTCA/GAAA-3'), an speci c regulatory factor formed and mediated cooperative gene activation [9][10]. The mechanisms of BATF regulation are diverse.…”