Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. Tumor metastasis is one of the major causes of high mortality of HCC. Identifying underlying key factors contributing to invasion and metastasis is critical to understand the molecular mechanisms of HCC metastasis. Here, we identified RNA binding protein L23 (RPL23) as a tumor metastasis driver in HCC. RPL23 was significantly upregulated in HCC tissues compared to adjacent normal tissues, and closely related to poor clinical outcomes in HCC patients. RPL23 depletion inhibited HCC cell proliferation, migration and invasion, and distant metastasis. Mechanistically, RPL23 directly associated with 3’UTR of MMP9, therefore positively regulated MMP9 expression. In conclusion, we identified that RPL23 might play an important role in HCC metastasis in an MMP9-dependent manner and be a potential therapeutic target for HCC tumorigenesis and metastasis.
Highlights
Hepatocellular carcinoma (HCC) is the predominant malignancy of the liver and ranks as the third most common cause of cancer-related death worldwide [1, 2]
To broadly investigate the potential function of ribosomal protein L23 (RPL23) in HCC, the expression of RPL23 was first analyzed in 2 published datasets, The Cancer Genome Atlas Cohort (TCGA) and Gene Expression Omnibus (GEO)
Kaplan-Meier analysis showed that patients with higher levels of RPL23 had shorter disease-free survival (DFS; Figure 1E, HR=1.4, p=0.045) and overall survival (OS; Figure 1F, HR=1.6, p=0.0069), suggesting that upregulation of RPL23 was closely related to poor clinical outcomes in HCC
Summary
Hepatocellular carcinoma (HCC) is the predominant malignancy of the liver and ranks as the third most common cause of cancer-related death worldwide [1, 2]. Growing number of studies have revealed that altered RNA metabolism due to dysfunction of RBP plays an important role in cancer progression, especially cancer cell metastasis [9, 10]. Meng and co-workers confirmed that RPL23MDM2-p53 pathway could coordinate with the p19ARFMDM2-p53 pathway against oncogenic RAS-induced tumorigenesis [14]. Much of those studies on RPL23 focus on its effect in cell apoptosis, the underlying functions and mechanisms of RPL23 in HCC metastasis has been underestimated. The aim of this study is to examine the effects of RPL23 on the metastasis of HCC and to elucidate the underlying mechanisms
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