Ribosomal Protein L23 Drives the Metastasis of Hepatocellular Carcinoma via Upregulating MMP9

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.

Detecting early‐warning biomarkers associated with heart‐exosome genetic‐signature for acute myocardial infarction: A source‐tracking study of exosome

“…14 RPL23 is a gene that encodes ribosomal protein L23 and its high gene expression level relates to unfavourable events in diverse cancer diseases. [16][17][18] Herein, we demonstrated that the RPL23 gene expression level was elevated in AMI exosome samples. Furthermore, our analysis indicated that RPL23 was positively correlated with the fractions of monocyte-derived exosomes and negatively correlated with the fractions of resting mast cell-derived exosomes.…”

“…RPL23 is a gene that encodes ribosomal protein L23 and its high gene expression level relates to unfavourable events in diverse cancer diseases 16–18 . Herein, we demonstrated that the RPL23 gene expression level was elevated in AMI exosome samples.…”

Ribosomal protein L32 enhances hepatocellular carcinoma progression

“…Increasing evidence shows that there are about 80 kinds of ribosomal proteins in eukaryotes, which not only function to form ribosomes and bind RNA but also have other functions, such as participating in tumor development and regulating tumor resistance to drugs 11,21 . Today, many ribosomal proteins have been found to be involved in regulating the occurrence and development of a variety of cancers, including lung, breast, and liver cancers 11,12,22 . In addition, RNA‐binding protein (RBP), a key regulator of gene expression, is involved in the progression of many cancers, such as HCC 22–24 .…”

“… 11 , 21 Today, many ribosomal proteins have been found to be involved in regulating the occurrence and development of a variety of cancers, including lung, breast, and liver cancers. 11 , 12 , 22 In addition, RNA‐binding protein (RBP), a key regulator of gene expression, is involved in the progression of many cancers, such as HCC. 22 , 23 , 24 A total of 526 RBPs were abnormally expressed in HCC compared to normal adjacent liver tissues and predicted poor prognosis.…”

“… 11 , 12 , 22 In addition, RNA‐binding protein (RBP), a key regulator of gene expression, is involved in the progression of many cancers, such as HCC. 22 , 23 , 24 A total of 526 RBPs were abnormally expressed in HCC compared to normal adjacent liver tissues and predicted poor prognosis. 25 A study showed that abnormal expression of RBPs in HCC enhanced tumor metastasis and accelerated tumor progression.…”