Abstract
Alternative polyadenylation (APA), a post-transcriptional modification, has been implicated in many diseases, but especially in tumor proliferation. CFIm25, the 25 kDa subunit of human cleavage factor Im (CFIm), is a key factor in APA. We show that CFIm25 expression is reduced in human hepatocellular carcinoma (HCC), and its expression correlates with metastasis. Kaplan-Meier analysis indicated that CFIm25 is related to overall survival in HCC. Moreover, CFIm25 expression is negatively related to the metastatic potential of HCC cell lines. CFIm25 knockdown promotes cell invasion and migration in vitro, while overexpression of CFIm25 inhibits cell invasion and migration in vitro and inhibits intrahepatic and lung metastasis in vivo. Additional studies showed that CFIm25 disrupts epithelial-mesenchymal transition by increasing E-cadherin, that it inhibits HCC cell migration and invasion by blocking the p38 and JNK/c-Jun signaling pathways, and that CFIm25 knockdown increases the transcriptional activity of activating protein-1 (AP-1). These findings indicate that therapy directed at increasing CFIm25 expression is a potential HCC treatment.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancerrelated death worldwide
We show that CFIm25 expression is reduced in human hepatocellular carcinoma (HCC), and its expression correlates with metastasis
Additional studies showed that CFIm25 disrupts epithelial-mesenchymal transition by increasing E-cadherin, that it inhibits HCC cell migration and invasion by blocking the p38 and JNK/c-Jun signaling pathways, and that CFIm25 knockdown increases the transcriptional activity of activating protein-1 (AP-1)
Summary
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancerrelated death worldwide. It has a yearly fatality ratio of approximately 1, indicating that most patients do not survive one year [1]. HCC develops in cirrhotic patients in up to 90% of cases, mainly related to chronic viral hepatitis and alcohol abuse [2]. Invasion and metastasis are the underlying causes of poor long-term survival after clinical treatment in HCC [3]. HCC metastasis is a complex process that involves multiple factors, and its mechanism is not fully understood [4]. In-depth research on the molecular mechanism of HCC metastasis might discover a potential intervention therapy
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