Abstract
In this study, we investigated the value of measurement of the chemokine CXCL1 in clinical management of hepatocellular carcinoma (HCC) and its possible role in the molecular pathogenesis of HCC. High CXCL1 expression predicted recurrence in HCC patients and promoted tumor progression in both in vivo and in vitro experimental systems. Overexpression of CXCL1 increased mitochondrial metabolism and activated the epithelial-to-mesenchymal transition (EMT). Using computational analysis we identified the microRNA miR-200a as a putative post-transcriptional regulator of CXCL1. We found that levels of miR-200a were inversely correlated with CXCL1 expression in HCC patient tissue samples by northern blot and qRT-PCR. Furthermore, CXCL1 was identified as a direct target which was bound and inhibited by miR- 200a. These findings provide new insights into the role of CXCL1 in HCC and its post-transcriptional regulation and suggest it may be a prognostic indicator for poor outcomes and a potential target for therapy.
Highlights
Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related mortalities
We found that levels of miR-200a were inversely correlated with CXCL1 expression in hepatocellular carcinoma (HCC) patient tissue samples by northern blot and qRT-PCR
Chemokines secreted by inflammatory cells and tumor cells could recruit other inflammatory cells into the tumor microenviroment, but may affect tumor growth, invasion, angiogenesis, and metastasis through corresponding cell surface receptors [14]
Summary
Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related mortalities. Nearly 750,000 new patients are diagnosed with liver cancer each year [1]. Biologically-targeted therapies and surgical interventions have progressed, the overall 5 year recurrence rate after hepatectomy remains as high as 70% [2]. To provide new prognostic indicators and targeted therapies for improved clinical management, the underlying molecular mechanisms of HCC need to be further investigated. Chemokines are small molecular weight proteins (8–13 KD) that drive the migration of a variety of immune cells [3]. Nonparenchymal liver cells, including hepatic stellate cells, hepatic dendritic cells, neutrophils, monocytes, and Kupffer cells, secrete CXCL1 and other chemokines to recruit immune cells and modify the HCC tumor microenvironment [10]
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