MARCH1 encourages tumour progression of hepatocellular carcinoma via regulation of PI3K‐AKT‐β‐catenin pathways

Abstract

Membrane‐associated RING‐CH‐1 (MARCH1) is a membrane‐anchored E3 ubiquitin ligase that is involved in a variety of cellular processes. MARCH1 was aberrantly expressed as a tumour promoter in ovarian cancer, but the signalling about the molecular mechanism has not yet been fully illuminated. Here, we first determined that MARCH1 was obviously highly expressed in human hepatocellular carcinoma samples and cells. In addition, our findings demonstrated that the proliferation, migration and invasion of hepatocellular carcinoma were suppressed, but the apoptosis was increased, as a result of MARCH1 knockdown by either siRNA targeting MARCH1 or pirarubicin treatment. Conversely, the proliferation, migration and invasion of hepatocellular carcinoma were obviously accelerated, and the apoptosis was decreased, by transfecting the MARCH1 plasmid to make MARCH1 overexpressed. Moreover, in vivo, the results exhibited a significant inhibition of the growth of hepatocellular carcinoma in nude mice, which were given an intra‐tumour injection of siRNA targeting MARCH1. Furthermore, our study concluded that MARCH1 functions as a tumour promoter, and its role was up‐regulated the PI3K‐AKT‐β‐catenin pathways both in vitro and in vivo. In summary, our work determined that MARCH1 has an important role in the development and progression of hepatocellular carcinoma and may be used as a novel potential molecular therapeutic target in the future treatment of hepatocellular carcinoma.

Erianin suppresses hepatocellular carcinoma cells through down-regulation of PI3K/AKT, p38 and ERK MAPK signaling pathways

“…Also, several reports showed that the PI3K pathway might be related to tumorigenesis and tumor development [9,20]. According to the clinical research, p-AKT was higher in the tumor (53%) than in cirrhotic tissues (12%) while it was absent from normal liver [21]. PI3K/Akt signaling pathway is also confirmed to be associated with poor survival, high tumor grade, intrahepatic metastasis, as well as vascular invasion in HCC patients.…”

The Membrane-Associated MARCH E3 Ligase Family: Emerging Roles in Immune Regulation

“…For examples, expression of MARCH1 is up-regulated following TNFα, IL-1β, and TGFβ stimulation (54). The transcription of MARCH1 gene is induced by IL-10 and LPS in monocytes or DCs, while its expression is decreased during maturation of DCs, indicating that MARCH1 plays important roles in regulating antigen presentation and DC maturation (22, 25, 31, 33, 34, 55). The transcription of MARCH9 gene is increased in human DCs upon Toll-like receptor (TLR) 3 or 4 activation (22).…”

“…The transcription of MARCH3 gene is dramatically induced by LPS and TLR8 agonist in monocytes (56). Notably, it has been demonstrated that MARCH1 is highly expressed in human hepatocellular carcinoma (HCC) cells (55), MARCH5 is up-regulated in ovarian cancer tissues (28), and MARCH8 is highly expressed in esophageal tumors and associated with tumor aggression (50). These studies suggest that certain MARCH proteins may involve in tumorigenesis.…”

Uncovering Prognosis-Related Genes and Pathways by Multi-Omics Analysis in Lung Cancer

“…It suggests that multi-omics analysis, including epigenetic data, could improve availability of output, in terms of precision medicine or personalized medicine, as we recently reported [65]. The E3 ubiquitin ligase MARCH1 plays an important role in immunology [66], although only a few publications have focused on MARCH1 in the context of cancer [67,68]. Therefore, further studies in this area are required and could have the potential to contribute to the field of cancer research, and more particularly lung cancer.…”