Ursolic acid-downregulated long noncoding RNA ASMTL-AS1 inhibits renal cell carcinoma growth via binding to HuR and reducing vascular endothelial growth factor expression

by Selleckchem | Sep 12 2023

It has been reported ursolic acid (UA), one of the naturally abundant pentacyclic triterpenes, possesses a wide range of biological activities including anti-inflammatory, anti-atherosclerotic, and anticancer properties. Renal cell carcinoma (RCC) is a severe malignancy due to its asymptomatically spreading ability. Our study aimed to investigate the role and molecular mechanism of UA in RCC. RCC cell proliferation, migration, invasion, and angiogenesis were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Transwell, and tube formation assays. Xenograft tumor models were established to confirm the role of UA and long noncoding RNA ASMTL antisense RNA 1 (ASMTL-AS1) in vivo. Expression levels of ASMTL-AS1 and vascular endothelial growth factor (VEGF) were measured using reverse transcriptase quantitative polymerase chain reaction and western blot analysis. The interaction probabilities of ASMTL-AS1 or VEGF with RNA-binding protein human antigen R (HuR) were verified by RNA immunoprecipitation experiment. The half-life period of messenger RNA (mRNA) was determined using actinomycin D. UA inhibited RCC cell growth in vivo and tumorigenesis in vitro. ASMTL-AS1 was highly expressed in RCC cell lines. Of note, UA downregulated ASMTL-AS1 expression, and overexpressed ASMTL-AS1 reversed the UA-induced suppression on RCC cell migration, invasion, and tube formation. Additionally, ASMTL-AS1 bound to HuR to maintain the stability of VEGF mRNA. Rescue experiments showed that the suppressed malignancy of RCC cells mediated by ASMTL-AS1 knockdown was counteracted by overexpression of VEGF. Moreover, silenced ASMTL-AS1 inhibited RCC tumor growth and metastasis in vivo. The obtained data suggest UA as a promising therapeutic agent to attenuate the development of RCC via regulation of the targeted molecules.

Comments:

The reported study aimed to investigate the role and molecular mechanism of ursolic acid (UA) in renal cell carcinoma (RCC). RCC is a severe malignancy known for its ability to spread asymptomatically. UA is a naturally abundant pentacyclic triterpene with various biological activities, including anti-inflammatory, anti-atherosclerotic, and anticancer properties.

To evaluate the effects of UA on RCC, the researchers conducted several experiments. They assessed RCC cell proliferation, migration, invasion, and angiogenesis using assays such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Transwell, and tube formation assays. Additionally, xenograft tumor models were established to confirm the role of UA and a specific long noncoding RNA called ASMTL antisense RNA 1 (ASMTL-AS1) in vivo.

The expression levels of ASMTL-AS1 and vascular endothelial growth factor (VEGF) were measured using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The researchers also investigated the interaction probabilities of ASMTL-AS1 or VEGF with a RNA-binding protein called human antigen R (HuR) through RNA immunoprecipitation experiments. They determined the half-life period of messenger RNA (mRNA) using actinomycin D.

The results of the study showed that UA inhibited RCC cell growth in vivo and tumorigenesis in vitro. The expression of ASMTL-AS1 was found to be high in RCC cell lines. Notably, UA downregulated the expression of ASMTL-AS1, and overexpressing ASMTL-AS1 reversed the suppressive effects of UA on RCC cell migration, invasion, and tube formation. Furthermore, the researchers found that ASMTL-AS1 bound to HuR to maintain the stability of VEGF mRNA. Rescue experiments demonstrated that the suppressed malignancy of RCC cells resulting from ASMTL-AS1 knockdown could be counteracted by overexpressing VEGF. Moreover, silencing ASMTL-AS1 inhibited RCC tumor growth and metastasis in vivo.

Based on these findings, the study suggests that UA could be a promising therapeutic agent for attenuating the development of RCC through its regulation of targeted molecules. The downregulation of ASMTL-AS1 and the subsequent destabilization of VEGF mRNA may contribute to the anti-cancer effects of UA in RCC.