<p>MEX3C regulates lipid metabolism to promote bladder tumorigenesis through JNK pathway</p>

Abstract

Purpose: Bladder cancer (BC) is the most common urinary cancer among men with a high rate of deaths despite the improved medical technology and treatment. Recent evidence demonstrated that Mex-3 RNA-Binding Family Member C (MEX3C) plays various roles in different biological activities, but its molecular mechanisms underlying the pathogenesis of BC remain unclear yet. The aim of this research was to explore the expression patterns of MEX3C and its biological functions in human BC. Materials and methods: The Cancer Genome Atlas (TCGA) and Oncomine databases were jointly used to analyze the expression of MEX3C in BC and its correlation with the clinicopathological features, while real-time PCR and immunohistochemistry analysis were used to verify the predicted results. Wound-healing assay, Matrigel invasion assay, BODIPY staining and Western blot analysis were used in a cell model to assess the effect of MEX3C on the lipid metabolism, invasion and migration of BC and its mechanisms. Results: MEX3C was highly expressed in BC tissues and cells compared with their normal counterparts, and its expression was positively correlated with the clinicopathological features, especially the invasiveness phenotype. Overexpression of MEX3C accumulated lipid droplets and promoted cell adhesion, invasion and migration. We further demonstrated that MEX3C regulated lipid metabolism and promoted tumor development and progression through activation of JNK signaling and upregulating the JNK downstream protein levels of sterol regulatory element-binding proteins-1, fatty acid synthase and acetyl-CoA carboxylase-1. Conclusion: Here we identified MEX3C as a new oncogene to promote bladder tumorigenesis by regulating lipid metabolism through Mitogen-activated protein kinase/c-Jun N-terminal kinase (MAPK/JNK) pathway. These findings suggest a new role of MEX3C in promoting BC tumorigenesis and provide a novel biomarker or molecular target for diagnosis or treating BC.

Molecular heterogeneity in breast carcinoma cells with increased invasive capacities

“…Spindle-like form of the INV cells with more pronounced filopodia formation, diminished number of lipid droplets and their translocation to the filopodia tips result in cell abilities to pass the biological barriers and use the energy from the lipid droplets. 29,30 As it was expected, all three INV cell lines belonging to different subtypes of breast cancer showed the enhanced migratory and invasive abilities. Although the parental breast carcinoma cells had equal invasive and migratory properties, and the procedure to obtain new cell lines with increased invasiveness was common for all investigated cells, Her2-positive Au565-INV cells revealed the most pronounced augmentation of the capacities to invade and migrate through the collagen-and laminin-coated membranes compared to other INV cells.…”

RNA packaging into extracellular vesicles: An orchestra of RNA‐binding proteins?

“…MEX3C1, the longest isoform with 659 amino acid residues, was found overexpressed in cells of the innate immune system and in different types of tumours, such as breast, liver, and bladder cancer, where it displayed oncogenic properties by regulating lipid metabolism (Chao et al., 2019). Other evidence suggested it may play a role in regulating energy balance (Han et al., 2014), stem cell self‐renewal and differentiation, and it contributed to hypertension susceptibility (Guzmán et al., 2006).…”

The RNA-Binding Ubiquitin Ligase MEX3A Affects Glioblastoma Tumorigenesis by Inducing Ubiquitylation and Degradation of RIG-I

“…Human MEX3 proteins consist of two N-terminal K homology (KH) domains, which provide RNA-binding ability, and a C-terminal RING finger module that confers ubiquitin E3-ligase activity [19]. MEX3 proteins play pivotal role in self-renewal and differentiation processes, with implications regarding stemness and carcinogenesis [20][21][22][23][24][25]. In particular, alterations of MEX3A activity have been described in gastric, colorectal and bladder cancers, although its mechanism of action and its potential substrates remain still elusive [21][22][23][24]26].…”