Silencing proline-rich coiled-coil 2C inhibit the proliferation and metastasis of liver cancer cells.

BACKGROUND

Proline-rich coiled-coil 2C () is located in the chromosome region lq where hepatocellular carcinoma (HCC) frequently undergoes genomic fragment amplification, but its role in HCC is unknown. In this study, we aimed to explore the correlation of with HCC diagnosis and progression, as well as its influence on the biological behavior of HCC cells.

METHODS

The Cancer Genome Atlas (TCGA) RNA-sequencing datasets of 371 cases of primary liver cancer and 50 normal liver tissue specimens were obtained to analyze correlation between expression and HCC staging, grades, and overall survival. After confirming expression of in HCC cells, silencing was performed. cell counting, cell clone formation, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and Flow cytometry were used to detect the cell proliferation and apoptosis; wound healing and Transwell assays were used to detect the invasion abilities of cells. Xenograft transplantation in nude mice was performed to investigate the impact of knockdown on tumorigenic capabilities. In addition, the expression levels of EMT (epithelial-mesenchymal transition)-related genes, including E-cadherin, N-cadherin, Twistl, Snail, Slug, and Smad2/3/4, were detected.

RESULTS

Analysis of TCGA data sets revealed that patients with high expression had significantly shorter overall survival. was abundantly expressed in four human hepatocarcinoma cell lines. After knockdown , the proliferation of HCC cells were suppressed and the numbers of apoptotic cells increased. Migration and invasion ability of HCC cells were inhibited by knockdown. Meanwhile, silencing inhibited the tumor formation (indicated by reduced tumor volume and weight compared to the control group) in BALB/c (Bagg Albino Laboratory-bred strain) nude mice. The expressions of EMT-related genes N-cadherin and Vimentin were significantly lower in the knockdown group than in the control group.

CONCLUSIONS

promotes the proliferation and metastasis of liver cancer cells and inhibited apoptosis, potentially through upregulation of EMT related N-cadherin and Vimentin.