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

Abstract

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.

Extraction, purification and anticancer activity studies on triterpenes from pomegranate peel

“…19 Ursolic acid inhibits renal cell carcinoma growth by binding to HuR and reducing the vascular endothelial growth factor expression. 47 Our results showed that TPP had a wide range of anticancer activities, and the inhibition of TPP on H460 cells was most obvious in a dose-dependent manner. TPP had a significant antiproliferative effect, and it could reduce cell viability to 50% within 48 h. This is closely linked to the anticancer activity of the triterpenes in TPP.…”

Comparative In Vitro Study: Assessing Phytochemical, Antioxidant, Antimicrobial, and Anticancer Properties of Vaccinium macrocarpon Aiton and Vaccinium oxycoccos L. Fruit Extracts

“…The anticancer activity of ursolic and oleanolic acids has been established against various cell lines [ 64 ]. Cai et al found that ursolic acid inhibited the migratory activity of CaKi-1 cells, reduced the ability of CaKi-1 cells to form renal tubules, and reduced the volume and weight of CaKi-1 cell tumors [ 65 ]. Vilkickytė et al investigated the fractions of triterpene compounds isolated from lingonberry fruit ( Vaccinium vitis-idea L.) and found that the fraction consisting of oleanolic and ursolic acids exhibited the strongest cytotoxic activity against the CaKi-1 cell line (the EC 50 was 4.5 µg/mL) [ 66 ].…”