Suppression of the nuclear transporter-KPNβ1 expression inhibits tumor proliferation in hepatocellular carcinoma

Med Oncol. 2015 Apr;32(4):128. doi: 10.1007/s12032-015-0559-1. Epub 2015 Mar 21.

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the malignant tumors and leads to the highly death in the solid tumors, but its mechanism remains unclear. KPNβ1 is one of the soluble nuclear transport receptors, has been reported to act as an important role in the occurrence and development of tumor, such as cervical cancer, head and neck and lung cancer. However, the expression mechanisms and physiological significance of KPNβ1 in HCC is still unclear.

Aim: The expression of KPNβ1 and its involvement in HCC was studied.

Methods: The expression of KPNβ1 protein was measured by Western blot and immunohistochemistry in HCC. We analyzed the effects of growth and interference of KPNβ1 in the cell cycle process by CCK8 and flow cytometrical analysis.

Results: KPNβ1 protein level was up-regulated in HCC tissue samples. The KPNβ1 expression was significantly associated with histological differentiation. The levels of KPNβ1 were significantly correlated with histological grade (P = 0.03), metastasis (P = 0.01), vein invasion (P = 0.04) and tumor size (P = 0.01) in HCC samples. Serum starvation assay proved that KPNβ1 was arrested in G1 phase and was gradually reduced by refeeding serum. Moreover, the knockdown of KPNβ1 induced cell proliferation arrest in HepG2 cell. Western blot analyses showed that KPNβ1 was correlated with NF-кB signaling pathway.

Conclusions: Our datum showed that KPNβ1 expression was up-regulated in HCC tissue samples and increasing HCC cells growth and the KPNβ1 expression was associated with poor survival. KPNβ1 may take part in the pathogenesis of hepatocellular carcinoma via NF-кB signaling pathway and serve as an independent prognostic indicator and a novel therapeutic target for HCC.

Publication types

  • Comparative Study
  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blotting, Western
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / secondary*
  • Case-Control Studies
  • Cell Proliferation*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Liver / metabolism*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Prognosis
  • RNA, Small Interfering / genetics
  • Survival Rate
  • Tumor Cells, Cultured
  • Young Adult
  • beta Karyopherins / antagonists & inhibitors*
  • beta Karyopherins / genetics
  • beta Karyopherins / metabolism

Substances

  • KPNB1 protein, human
  • RNA, Small Interfering
  • beta Karyopherins