Pinin associates with prognosis of hepatocellular carcinoma through promoting cell proliferation and suppressing glucose deprivation-induced apoptosis

Abstract

The roles of Pinin have been well studied in epithelial cell-cell adhesion and RNA alternative splicing, which suggests its involvement in cancer progression. However, little is known about the association between Pinin expression and hepatocellular carcinoma (HCC) tumorigenesis. In this study we report increased expression of Pinin in HCC tissues and cells. Elevated levels of Pinin closely associates with pathological grade and overall survival of patients with hepatocellular carcinoma. Suppression of Pinin expression via lentivirus mediated shRNA knockdown inhibits HCC cell proliferation, colony formation, cell viability, but promotes glucose deprivation (GD)-induced cell apoptosis. On the contrary, overexpression of Pinin reverses these effects observed in Pinin depleted cells. Meanwhile, overexpression of Pinin attenuates GD initiated poly ADP-ribose polymerase (PARP) cleavage and ERK1/2 dephosphorylation, which can be completely blocked with MEK1/2 inhibitor U0126. Therefore, we conclude that Pinin contributes to HCC progression and resistance to GD-induced apoptosis via maintaining ERK1/2 activation and hence may be a potential therapeutic target in hepatocellular carcinoma treatment.

RNA sequencing reveals PNN and KCNQ1OT1 as predictive biomarkers of clinical outcome in stage III colorectal cancer patients treated with adjuvant chemotherapy

“…Some evidences suggest that mechanisms and function of PNN are mainly related to the activation of EGFR/ERK signaling pathway . In addition, the observed processes of proliferation, invasion and metastasis have been suggested to be promoted by the upregulation of PNN . Our findings are in agreement with available literature data.…”

“…Higher PNN mRNA and/or Pinin protein expression levels were observed in tissues from ovarian carcinoma, hepatocellular carcinoma and CRC compared to the relative matched normal mucosa tissues. In these studies, high levels of PNN and/or Pinin were also associated with poor prognosis . A role of PNN in epithelial–mesenchymal transition has been suggested.…”

“…However, more recently, studies performed also in other cancers suggested a role of PNN in prognosis and in resistance to chemotherapy . Higher PNN mRNA and/or Pinin protein expression levels were observed in tissues from ovarian carcinoma, hepatocellular carcinoma and CRC compared to the relative matched normal mucosa tissues. In these studies, high levels of PNN and/or Pinin were also associated with poor prognosis .…”

“…PNN was successively supposed to be a tumor suppressor gene in renal cell carcinomas by genetic location and CpG islands methylation analysis . However, more recently, studies performed also in other cancers suggested a role of PNN in prognosis and in resistance to chemotherapy . Higher PNN mRNA and/or Pinin protein expression levels were observed in tissues from ovarian carcinoma, hepatocellular carcinoma and CRC compared to the relative matched normal mucosa tissues.…”

“…reported that Pinin resembles other epithelial markers such as E‐cadherin and play a role in ovarian tumorigenesis and progression. Some evidences suggest that mechanisms and function of PNN are mainly related to the activation of EGFR/ERK signaling pathway . In addition, the observed processes of proliferation, invasion and metastasis have been suggested to be promoted by the upregulation of PNN .…”