MARCH8 is associated with poor prognosis in non-small cell lung cancers patients.

Jiye Fan,Jing Zhang,Manli Li,Shu-Hong Huang,Baohua Zhao,Liying Tian

doi:10.18632/oncotarget.22602

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.

Highlights

Lung cancer involves malignant tumors and is very harmful to humans
Members of the membrane-associated RING-CH (MARCH) family have a wide variety of cell functions, including immune regulation, membrane transport and endoplasmic reticulumassociated degradation (ERAD).We first analyzed the expression of the MARCH family using Gene Expression Profiling Interactive Analysis (GEPIA), which is an online tool for transcriptomic analysis based on the Cancer Genome Atlas (TCGA) and the GenotypeTissue Expression (GTEx) dataset [9]
Because the expression of Membrane-associated RING-CH 8 (MARCH8) was significantly different in cancer and normal tissues, we investigated the association between MARCH8 expression level and survival rates of lung cancer patients

Summary

Introduction

Lung cancer involves malignant tumors and is very harmful to humans. More than 80 percent of lung cancers are classified as non-small cell lung cancer (NSCLC) [1]. Even though treatment modalities have improved over time, the 5-year survival rate is still less than 15 percent. This is mainly due to relapse and metastasis [2]. The physiological roles of MARCH8 in lung cancer remain largely unknown. We sought to determine the crucial roles MARCH8 plays in NSCLC against carcinogenesis and its progression

Methods

Results

Conclusion