BICD1 functions as a prognostic biomarker and promotes hepatocellular carcinoma progression

Pathol Res Pract. 2020 Apr;216(4):152858. doi: 10.1016/j.prp.2020.152858. Epub 2020 Feb 12.

Abstract

Hepatocellular carcinoma (HCC) is the most predominant type of primary liver cancer and has a high degree of malignancy as well as mortality rate. Many drivers are involved in the development and progression of HCC. A recent study has reported that high BICD cargo adaptor 1 (BICD1) expression indicates poor prognosis of glioblastoma. But, the expression and biological function of BICD1 in HCC remain unclear. In current study, we found that the expression of BICD1 was markedly up-regulated in HCC tissues compared to adjacent nontumor tissues. GEPIA dataset and GSE datasets were consistently indicated the elevated expression of BICD1 in HCC. Furthermore, BICD1 was highly expressed in HCC cell lines including Hep3B, Huh7, MHCC97H and HCCLM3 as compared with that in LO2 cells. High BICD1 expression was positively correlated with malignant clinical features, such as tumor size ≥ 5 cm, venous infiltration and advanced tumor stages. HCC patients highly expressing BICD1 showed a significant shorter overall survival compared to BICD1 low-expression cases. Moreover, TCGA-LIHC data further demonstrated that the up-regulated BICD1 expression predicted poor prognosis of HCC patients. Next, we revealed that BICD1 knockdown prominently suppressed the proliferation, migration and invasion of HCCLM3 cells. Conversely, ectopic expression of BICD1 remarkably facilitated these malignant behaviors of Hep3B cells. Interestingly, BICD1 knockdown abolished hypoxia-induced HCC cell proliferation, migration and invasion. In conclusion, we provide the first evidence to support that BICD1 functions as a predictor for the prognosis of HCC and may serve as a promising therapeutic target for further HCC treatment.

Keywords: BICD1; Hepatocellular carcinoma; Hypoxia; Metastasis; Tumor growth.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / pathology*
  • Cytoskeletal Proteins / metabolism*
  • Disease Progression
  • Female
  • Humans
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Prognosis

Substances

  • Adaptor Proteins, Signal Transducing
  • BICD1 protein, human
  • Biomarkers, Tumor
  • Cytoskeletal Proteins