Abstract
This paper aims to investigate the function of structural maintenance of chromosome 4 (SMC4) in the progression of hepatocellular carcinoma (HCC) under hypoxic condition. In this study, we found that suppression of SMC4 could inhibit proliferation and migration of HCC cells through inducing G1 phase arrest and affecting process of epithelial-mesenchymal transition (EMT) under hypoxic condition. Moreover, we demonstrated that SMC4 was transcriptionally regulated by hypoxia-inducible factor-1 (HIF-1) under hypoxic condition. As SMC has been shown to be a target gene of miR-219, we observed that miR-219 was downregulated under hypoxic condition and suppression of HIF-1a could lead to the upregulation of miR-219. We also proved that miR-219 could affect the proliferation and migration of HCC cells under hypoxic condition. In conclusion, our study demonstrated a novel HIF-1-miR-219-SMC4 regulatory pathway under hypoxic condition in HCC cells.
Highlights
Hepatocellular carcinoma (HCC) is the most common digestive system tumor, which is highly prevalent in the world and is prominent in China [1]
Recent studies demonstrated that Structural maintenance of chromosome 4 (SMC4) was associated with tumor dedifferentiation, advanced stage, and vascular invasion of primary liver cancer, and further study proved that SMC4 was a target gene regulated by miR-219 and affected the progression of HCC through activating JAK2/Stat3 pathway [4, 5]. us, SMC4 acted as a vital role in progression of HCC
We observed that suppression of SMC4 could inhibit proliferation and migration of HCC cells under hypoxic condition. en we demonstrated that SMC4 was transcriptionally regulated by hypoxiainducible factor-1 (HIF-1)
Summary
Hepatocellular carcinoma (HCC) is the most common digestive system tumor, which is highly prevalent in the world and is prominent in China [1]. Recent studies demonstrated that SMC4 was associated with tumor dedifferentiation, advanced stage, and vascular invasion of primary liver cancer, and further study proved that SMC4 was a target gene regulated by miR-219 and affected the progression of HCC through activating JAK2/Stat pathway [4, 5]. Recent studies have demonstrated that hypoxia is a common phenomenon in HCC, which could change gene transcription through stabilizing hypoxia-inducible factor (HIF) [6]. HIF-1 is a key transcription factor involved in the hypoxic response of cancer cells, which activates transcription of genes responsible for angiogenesis, glucose metabolism, proliferation, invasion, and metastasis in HCC [7]. Our study found a novel HIF-1-miR-219-SMC4 regulatory pathway under hypoxic condition in HCC cells
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