Increased expression of MARCH8, an E3 ubiquitin ligase, is associated with growth of esophageal tumor

Abstract

BackgroundHerein, for the first time, we report aberrant expression of membrane-associated RING-CH8 (MARCH8) in human esophageal squamous cell carcinoma. MARCH8 is a member of the recently discovered MARCH family of really interesting new genes (RING) E3 ligases. Though initial studies primarily focused on its immunomodulatory role, the newly discovered targets of this E3 ligase point towards its possible role in other biological processes such as embryogenesis and inhibition of apoptosis. However, its relevance in cancers is yet to be elucidated.MethodsWe carried out quantitative real time PCR and immunohistochemistry to examine the levels of MARCH8 mRNA and protein in esophageal squamous cell carcinoma tissues. The role of MARCH8 in esophageal cancer cells was evaluated by cell proliferation, clonogenic and migration/invasion assays and flow cytometry with MARCH8 gene knockdown.ResultsSignificantly increased expression of MARCH8 mRNA was found in esophageal squamous cell carcinoma as compared to distant matched non-malignant tissues (p = 0.024, AUC = 0.654). Immunohistochemical analysis revealed overexpression of MARCH8 protein in 86% of esophageal squamous cell carcinoma tissues (p < 0.001, AUC = 0.908). Interestingly, intense nuclear staining of MARCH8 protein was detected in cancer cells in addition to its cytoplasmic expression. Knockdown of MARCH8 resulted in decreased proliferation, migration, invasion and clonogenic potential of esophageal cancer cells. In addition to this, silencing of MARCH8 induced apoptosis in esophageal cancer cells which was measured by cell cycle distribution assay which showed increase in sub G0 and G2/M populations (cell death) and decrease in S-phase population. To further check the type of apoptosis induced by MARCH8 silencing, annexin assay was performed which showed significant increase in the number of cells in early apoptotic phase.ConclusionsOverall, increased expression of MARCH8 gene in preneoplastic and neoplastic esophageal tissues and its knockdown effect on cancer cell properties demonstrated herein points towards the potential role of this protein in esophageal tumorigenesis.

Proteomic profiling of milk small extracellular vesicles from bovine leukemia virus-infected cattle

“…Previous studies have been identified different types of proteins from blood or tumour tissues that were feasible in understanding the tumour progression in human. Some of the up/down-regulated proteins in our present study such as CNTFR, DDAH1, TUBB1, MARCH8, KRT1, KRT18, APOE, PDCD6, MMP2, ITGA6, MYOF, and TGFB2 were previously reported to be associated with certain tumorigenesis and progression in malignancies [22][23][24][25][26][27][28][29][30][31][32][33] . Taken together, these results indicated that as an oncogenic viral disease in cattle, BLV infection could alter the encapsulated sEV proteins; therefore, the new proteins are appearing within milk sEV.…”

MARCH9 Suppresses Lung Adenocarcinoma Progression by Downregulating ICAM-1

“…MARCH5 and MARCH7 can both promote the processes of migration and invasion in ovarian cancer cells [14,15]. High expression of MARCH8 was also observed in esophageal tumors and was associated with tumor aggression [16]. However, at present, there is no evidence about the role of MARCH9 in malignancy.…”

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

“…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.…”