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Published on: September 25, 2018
MARCH8 is associated with poor prognosis in non-small cell lung cancers patients
Jiye Fan1,2, Liying Tian2, Manli Li1
1Department of Biochemistry and Molecular Biology, College of Life Science, Hebei Normal University, Shijiazhuang, Hebei 050024, PR China.
Abstract:
MARCH8 belongs to a family of membrane-associated RING-CH (MARCH) ubiquitin ligases. The functions of MARCH8 have been thoroughly investigated but its mechanism of action remains unknown. In this study, we detected the expression of MARCH8 protein in NSCLC samples and identified MARCH8 mRNA expression through a TCGA database. In addition, we analyzed the correlation between MARCH8 and the clinical characteristics of NSCLC patients and their prognosis.(www.kmplot.com). The roles of MARCH8 in proliferation, migration, and metastasis were further explored through ectopic expression analysis and western blot analysis; its mechanism of expressionwas also explored. We discovered that MARCH8 was downregulated in NSCLC tissues compared to adjacent normal lung tissues. Overexpression of MARCH8 inhibited NSCLC cell proliferation and metastasis via the PI3K and mTOR signaling pathways; this also increased apoptosis of A549 and H1299 cells. Our results indicated that MARCH8 plays crucial roles in NSCLC against carcinogenesis and progression; therefore, MARCH8 might be a predictive factor and an attractive therapeutic target for NSCLC patients.
Insights
Membrane-associated RING-CH (MARCH) ligase 8 (MARCH8) is downregulated in non-small cell lung cancer (NSCLC). Overexpressing MARCH8 inhibits NSCLC progression by affecting cell proliferation, metastasis, and apoptosis via the PI3K/mTOR pathway.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MARCH8 is a ubiquitin ligase family member with an unknown mechanism of action.
- Understanding MARCH8's role in non-small cell lung cancer (NSCLC) is crucial for therapeutic development.
Purpose of the Study:
- To investigate MARCH8 expression in NSCLC tissues.
- To analyze the correlation between MARCH8 and NSCLC patient characteristics and prognosis.
- To explore the functional roles and molecular mechanisms of MARCH8 in NSCLC progression.
Main Methods:
- MARCH8 protein and mRNA expression analysis in NSCLC samples and TCGA database.
- Correlation analysis between MARCH8 expression and NSCLC clinical characteristics/prognosis.
- Ectopic expression, western blot, and cell apoptosis assays to investigate MARCH8 function in NSCLC cell lines (A549, H1299).
Main Results:
- MARCH8 was significantly downregulated in NSCLC tissues compared to adjacent normal tissues.
- Overexpression of MARCH8 suppressed NSCLC cell proliferation and metastasis.
- MARCH8 overexpression enhanced apoptosis in NSCLC cells, potentially through the PI3K and mTOR signaling pathways.
Conclusions:
- MARCH8 plays a critical role in suppressing NSCLC carcinogenesis and progression.
- MARCH8 may serve as a valuable predictive biomarker for NSCLC.
- MARCH8 represents a potential therapeutic target for NSCLC treatment.
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