Abstract
RNA-binding motif protein 8A (RBM8A) is abnormally overexpressed in hepatocellular carcinoma (HCC) and involved in the epithelial-mesenchymal transition (EMT). The EMT plays an important role in the development of drug resistance, suggesting that RBM8A may be involved in the regulation of oxaliplatin (OXA) resistance in HCC. Here we examined the potential involvement of RBM8A and its downstream pathways in OXA resistance using in vitro and in vivo models. RBM8A overexpression induced the EMT in OXA-resistant HCC cells, altering cell proliferation, apoptosis, migration, and invasion. Moreover, whole-genome microarrays combined with bioinformatics analysis revealed that RBM8A has a wide range of transcriptional regulatory capabilities in OXA-resistant HCC, including the ability to regulate several important tumor-related signaling pathways. In particular, histone deacetylase 9 (HDAC9) emerged as an important mediator of RBM8A activity related to OXA resistance. These data suggest that RBM8A and its related regulatory pathways represent potential markers of OXA resistance and therapeutic targets in HCC.
Highlights
Hepatocellular carcinoma (HCC) is a highly lethal cancer: it is the fifth most common malignant tumor globally, and its mortality rate ranks third among all cancers [1]
These results indicates that the expression level of RNA-binding motif protein 8A (RBM8A) may be related to OXA resistance in hepatocellular carcinoma (HCC)
Our study shows that RBM8A can induce epithelial-mesenchymal transition (EMT) in HCC cells, thereby affecting proliferation, apoptosis, migration, and invasion, as well as promoting OXA resistance
Summary
Hepatocellular carcinoma (HCC) is a highly lethal cancer: it is the fifth most common malignant tumor globally, and its mortality rate ranks third among all cancers [1]. The advent of the targeted drug sorafenib opened the door to advanced HCC drug therapies, but first-line therapies are associated with relatively low rates of objective response and progression-free survival [2]. Their inefficacy and elevated cost limit their clinical usefulness [3]. The complexity of HCC means that it needs to be treated through multiple approaches, including systemic chemotherapy. Oxaliplatin (OXA)-based systemic chemotherapy is a widely used treatment for advanced HCC in Asia, where good efficacy has been achieved [4,5,6]. Identifying the molecules and pathways that give rise to such resistance is critical
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