MAEL contributes to gastric cancer progression by promoting ILKAP degradation

Abstract

The cancer-testis gene MAEL is involved in the development and progression of bladder, liver and colorectal cancers. However, its role in other cancers is unclear. By systematically analyzing transcriptomics and genomics data from various cancer databases, we identified that the MAEL gene is aberrantly elevated in gastric cancer (GC) tissues and that its expression is strongly negatively correlated with DNA methylation (Pearson's correlation coefficient = −0.675). Survival analysis revealed that MAEL expression may serve as a prognostic marker for GC patients (overall survival: hazard ratio [HR] = 1.54, p = 1.2E-4; first progression: HR = 1.51, p = 8.7E-4). In vitro and in vivo experiments demonstrated that silencing MAEL expression in the GC cell lines HGC-27 and AGS inhibits proliferation, colony formation, migration, invasion and growth of xenograft tumors, whereas MAEL overexpression exerts the opposite effects in the normal gastric cell line GES-1. Mechanistically, MAEL promotes the lysosome-dependent degradation of the protein phosphatase ILKAP, leading to increased phosphorylation of its substrates (p38, CHK1 and RSK2). Moreover, adenovirus-mediated ILKAP overexpression reversed the oncogenic effects of MAEL in vitro and in vivo. Taken together, these results indicate that MAEL exerts its oncogenic function by promoting ILKAP degradation in the GC.

ZCCHC10 suppresses lung cancer progression and cisplatin resistance by attenuating MDM2-mediated p53 ubiquitination and degradation

“…The target sequences of ZCCHC10 shRNAs are listed in Supplementary Table S3. Infection and selection for stable cell lines were performed as described previously 20 .…”

“…Co-IP experiments were performed using endogenous proteins in Beas-2b and overexpressed proteins in Hek293 cells as previously described 18,20 . For analyzing the effect of ZCCHC10 on the interaction between p53 and MDM2, Hek293 cells were co-transfected with 3 μg of HA-p53 plasmid, 3 μg of Myc-MDM2C464A plasmid and an increasing amount (0, 3, 6, 9 μg) of EGFP-ZCCHC10 plasmid.…”

“…MTT assay, colony formation assay, wound healing assay, and transwell invasion assay were performed as described previously 20 .…”

“…For generating a xenograft tumor model, a total of 1 × 10 7 the A549 cells stably over-expressing ZCCHC10 and empty vector into the left and right dorsal flanks of nude mice, respectively. The tumor volume was measured as described previously 20 . At 56 days after injection, mice were sacrificed and the tumors were surgically dissected, embedded in paraffin for HE and IHC staining.…”

Genome-Wide Analysis of Methylation-Driven Genes and Identification of an Eight-Gene Panel for Prognosis Prediction in Breast Cancer

“…MAELSTROM protein (MAEL) is a novel diagnostic biomarker for gastric cancer. A previous study revealed that the function of MAEL is closely linked to epithelialmesenchymal transition (EMT) and stem cell properties (Zhang et al, 2017). Lck Interacting Transmembrane Adaptor 1 (LIME1) is a transmembrane adaptor involved in the activation of BCR (B-cell antigen receptor)-mediated signaling via interaction with Lck and Lyn (Hořejšì, 2004).…”