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.

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Introduction Seabuckthorn (Hippophae rhamnoides L.) is a high‐altitude plant with immense medicinal, nutritional, and therapeutic value. Earlier studies have documented the presence of various useful bioactive substances in this species; however, comprehensive metabolome profiling of seabuckthorn berries originating from different regions of the Indian Himalayas has not been undertaken. Objective Metabolomic profiling of seabuckthorn berries originating from different geographical sites in the Himachal Pradesh and Jammu & Kashmir regions of the Indian Himalayas was performed by using gas chromatography–mass spectrometry. Materials and methods The GC–MS metabolome profiles of seabuckthorn berries collected from different sites (altitude 1,400–4,270 m; average temperature 8°C–27°C) were subjected to multivariate analysis following principal component analysis and hierarchical clustering analysis. Results The GC–MS results showed substantial variability for berry metabolites, including fatty acids, alkyl ethers, and alkyl esters. Fatty acids and their esters were mainly responsible for the variation in the berry metabolome. The metabolite expression profile heat map revealed two distinct groups of seabuckthorn berries originating from Himachal Pradesh (Lahaul and Spiti) and Jammu & Kashmir (Leh, Nubra, and Kargil), the former showing higher expression of metabolites. Interestingly, a strong negative association existed between altitude and the amounts of metabolites such as amides, alkyl esters, alcohols, sugars, and sugar esters. In contrast, temperature showed a strong positive association with ketone and alkyl ether levels. Conclusion GC–MS profiling provides important phytochemical indicators to distinguish between seabuckthorn berries from different geographical sites. Our metabolome profiling analysis generated valuable information that will be useful in the formulation of various seabuckthorn products, benefiting farmers and industries.

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