TRIM36 inhibits tumorigenesis through the Wnt/β-catenin pathway and promotes caspase-dependent apoptosis in hepatocellular carcinoma

Abstract

Background Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has an extremely poor prognosis. We aimed to determine the latent relationships between TRIM36 regulation of apoptosis and the Wnt/β-catenin pathway in HCC. Methods Immunohistochemistry and western blotting were used to characterize the aberrant expression of TRIM36 in HCC and adjacent tissues. Clinical information was analyzed using Kaplan–Meier and Cox methods. RNA-seq of potential targets was conducted to detect the regulation of TRIM36. Apoptosis assays and cellular proliferation, invasion and migration were conducted in a loss- and gain-of-function manner in cultured cells to determine the biological functions of TRIM36. A rescue experiment was conducted to confirm the role of Wnt/β-catenin signaling in TRIM36 regulation. Finally, in vivo experiments were conducted using cell line-derived xenografts in nude mice to validate the central role of TRIM36 in HCC. Results TRIM36 expression was significantly downregulated in HCC tissues compared to adjacent non-tumor tissues. TRIM36 repressed the proliferation, migration, and invasion of Huh7 and HCCLM3 cells, whereas it stimulated apoptosis. Wnt/β-catenin signaling was inhibited by TRIM36, and rescue experiments highlighted its importance in HCC proliferation, migration, and invasion. In vivo experiments further confirmed the effects of sh-TRIM36 on HCC tumorigenesis, inhibition of apoptosis, and promotion of Wnt/β-catenin signaling. Conclusion Our study is the first to indicate that TRIM36 acts as a tumor suppressor in HCC. TRIM36 activates apoptosis and inhibits cellular proliferation, invasion, and migration via the Wnt/β-catenin pathway, which may serve as an important biomarker and promising therapeutic target for HCC.

Ghrelin promotes cardiomyocyte differentiation of adipose tissue‑derived mesenchymal stem cells by DDX17‑mediated regulation of the SFRP4/Wnt/β‑catenin axis

“…Based on the results of RNA-seq, the present study investigated genes that were associated with the Wnt/β-catenin signaling pathway, including TRIP6 ( 25 , 26 ), SOX30 ( 27 , 28 ), TRIM36 ( 29 , 30 ), DDX17 ( 31 – 33 ), WNK1 ( 34 , 35 ), TCF3 ( 36 ) and CCN1 ( 37 ). All of these genes have been reported to be associated with activation or inhibition of the Wnt signaling pathway in previously reported studies.…”

“…Following screening, TRIP6, SOX30, TRIM36, DDX17, WNK1, TCF3 and CCN1 were selected for further study; these genes were associated with the Wnt/β-catenin signaling pathway. Among these genes, TRIP6 (25,26), DDX17 (31)(32)(33), WNK1 (34,35) and CCN1 (37) are associated with the activation of the Wnt/β-catenin pathway and SOX30 (27,28), TRIM36 (29,30) and TCF3 (36) are associated with its inhibition. DDX17 has been reported to promote mRNA expression of myocyte enhancer factor 2C (MEF2C) and TNNT1 in myoblast cells (38) and serve a protective role in doxorubicin-induced cardiomyocyte injury (64).…”

m1A regulator-mediated methylation modification patterns correlated with autophagy to predict the prognosis of hepatocellular carcinoma

“…TRIM36 is a member of the TRIM family, multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. TRIM36 can inhibit tumorigenesis through the Wnt/β-catenin pathway and promote caspase-dependent apoptosis in HCC [ 51 ]. Take together, these 5 DEGs play an important regulatory role in the malignant phenotype of tumors, cancer prognosis may benefit from a model based on this 5 DEGs.…”