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PDZRN4 acts as a suppressor of cell proliferation in human liver cancer cell lines
Taotao Hu1,2, Hong Yang1,3, Ze-Guang Han1,4,2
1Key Laboratory of Systems Biomedicine (Ministry of Education) of Rui-Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Abstract:
Recently, some reports show that Ligand of Numb Protein-X 1 (LNX1) could be a suppressor gene in gliomas, while our current research has firstly shown that PDZ domain containing ring finger 4 (PDZRN4), another member of LNX family, could also be a potential suppressor in hepatocellular carcinoma (HCC). PDZRN4, also named LNX4 (Ligand of Numb Protein-X 4), is a member of the LNX family. We recently found that PDZRN4, but not LNX1, was down-regulated in HCC samples, and the role of PDZRN4 in the progression of HCC had not been studied before. To address this question, firstly, we evaluated the expression of PDZRN4 in HCC samples and adjacent non-cancerous tissues. Semi-quantitative polymerase chain reaction showed that PDZRN4 was down-regulated in 24/36 (66.7%) HCC samples separately. In addition, our research shows that PDZRN4 is silenced in all of the 12 HCC cell lines tested. Subsequently, cell-based functional assay exhibited that ectopic expression of PDZRN4 inhibits the proliferation, plate colony formation and anchorage-independent colony formation of HCC cells. Collectively, our results showed that PDZRN4 might be a potential tumour suppressor gene and had anti-proliferative effect on HCC cell proliferation, which would be of great significance to the researches on HCC.
Insights
PDZ domain containing ring finger 4 (PDZRN4) is down-regulated in hepatocellular carcinoma (HCC). Restoring PDZRN4 expression inhibits HCC cell proliferation, suggesting it acts as a tumor suppressor gene.
Area of Science:
- Oncology
- Molecular Biology
- Hepatology
Background:
- Ligand of Numb Protein-X 1 (LNX1) is implicated as a suppressor gene in gliomas.
- The role of PDZRN4 (also known as LNX4), another LNX family member, in hepatocellular carcinoma (HCC) progression was previously unstudied.
- LNX gene family members play diverse roles in cellular processes.
Purpose of the Study:
- To investigate the expression levels of PDZRN4 in HCC.
- To determine the functional role of PDZRN4 in HCC cell proliferation and colony formation.
- To evaluate PDZRN4 as a potential tumor suppressor in HCC.
Main Methods:
- Semi-quantitative polymerase chain reaction (PCR) to assess PDZRN4 expression in HCC tissues and cell lines.
- Cell-based functional assays to evaluate the impact of PDZRN4 ectopic expression on HCC cell proliferation, colony formation, and anchorage-independent growth.
Main Results:
- PDZRN4 was found to be down-regulated in 66.7% of HCC samples compared to adjacent non-cancerous tissues.
- PDZRN4 expression was silenced in all 12 tested HCC cell lines.
- Ectopic expression of PDZRN4 significantly inhibited HCC cell proliferation, plate colony formation, and anchorage-independent colony formation.
Conclusions:
- PDZRN4 exhibits down-regulation and silencing in hepatocellular carcinoma.
- PDZRN4 demonstrates anti-proliferative effects on HCC cells.
- PDZRN4 is identified as a potential tumor suppressor gene in HCC, significant for future research.
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