ciRS-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma

Abstract

Circular RNAs are a new class of non-coding RNAs that have been shown to play critical roles in the development and progression of renal cell carcinoma (RCC). However, little is known about the functional mechanisms and therapeutic role of ciRS-7 in RCC. A series of in vitro and in vivo experiments were performed to investigate the functional mechanism and therapeutic role of ciRS-7, such as real-time quantitative PCR, CCK-8, wound healing, transwell, colony formation, Edu, tumor xenograft and lung metastasis in NSG mice. RNA pull-down, dual luciferase reporter, fluorescence in situ hybridization (FISH) and rescue assays were used to determine the relationship between ciRS-7, miR-139-3p and TAGLN. In addition, we constructed PBAE/si-ciRS-7 nanocomplexes with PBAE material to evaluate the therapeutic effect of the nanocomplexes on tumor in vivo. ciRS-7 was highly expressed in RCC tumor tissues and cell lines, and high ciRS-7 expression correlated with tumor size, high Fuhrman grade and poor survival. Depletion of ciRS-7 significantly inhibited RCC cell proliferation, invasion, tumor growth and metastasis in vivo, while overexpression of ciRS-7 had the opposite effect. Mechanistically, ciRS-7 acts as a "ceRNA" for miR-139-3p to prevent TAGLN degradation and promoting RCC progression and metastasis via the PI3K/AKT signaling pathway. In addition, miR-139-3p mimics or inhibitor could reverse the altered malignant tumor behavior caused by ciRS-7 overexpression or silencing. Furthermore, the PBAE/siciRS-7 nanocomplexes could significantly inhibit RCC tumor progression and metastasis in vivo. ciRS-7 acts as a tumor promoter by regulating the miR-139-3p/TAGLN axis and activating the PI3K/AKT signaling pathway to promote RCC progression and metastasis. Drug development of PBAE/si-ciRS-7 nanocomplexes targeting ciRS-7 may represent a promising gene therapeutic strategy for RCC.

Identification of a Novel Defined Immune-Autophagy-Related Gene Signature Associated With Clinical and Prognostic Features of Kidney Renal Clear Cell Carcinoma

“…In recent years, targeted therapies against vascular endothelial growth factor (VEGF) and immunotherapy have gradually replaced nonspecific immune methods as the primary medical treatment for patients with KIRC ( Şenbabaoğlu et al, 2016 ; Barata and Rini, 2017 ; Smith et al, 2018 ; Dizman et al, 2020 ). Even though researchers have made some progress in this area, the selection of biomarkers, the combined use of drugs, and the ambiguity of immune checkpoints are still crucial issues that cannot be ignored ( Tang et al, 2013 ; Ghatalia et al, 2017 ; Mao et al, 2021 ). Therefore, studying the mechanism of the occurrence and development of clear cell RCC has become a clinically urgent need to solve the problem.…”

Characterization of an Autophagy-Immune Related Genes Score Signature and Prognostic Model and its Correlation with Immune Response for Bladder Cancer

“…2-ΔΔCT calculation method was used to calculate the relative expression levels of the target genes. 39 The primer sequences used in the present study are listed in Table S1 . According to the previously described method, 40 the clinical specimens were fixed in 4% paraformaldehyde, dehydrated in ethanol solution and embedded in paraffin.…”

Circular RNA Pvt1 oncogene (CircPVT1) promotes the progression of papillary thyroid carcinoma by activating the Wnt/β-catenin signaling pathway and modulating the ratio of microRNA-195 (miR-195) to vascular endothelial growth factor A (VEGFA) expression

“…with (invasion assays) or without (migration assays) the coating of Matrigel. According to previous study [ 39 ], the cells were seeded into serum-free medium and added to the upper chamber (1 × 10 4 cells per chamber) coated with 200 mg/mL of Matrigel. A medium containing 10% FBS was added to the lower chamber as a chemical attractant.…”