Downregulation of esophageal cancer-related gene 4 promotes proliferation and migration of hepatocellular carcinoma

Abstract

Esophageal cancer-related gene 4 (ECRG4) is a candidate tumor suppressor gene, which is involved in cell apoptosis, migration, infection and inflammation responsiveness; however, its expression level and clinical significance in hepatocellular carcinoma (HCC) remains unclear. In the present study, the authors aim to evaluate the clinical significance and potential role of ECRG4 in HCC. Level of ECRG4 protein expression in HCC and peripheral tissues was investigated in tissue specimens obtained from 56 consecutive HCC patients by immunohistochemistry. Cell proliferation, cell migration and invasion regulations were examined by MTT curves, flow cytometry, Transwell assays and western blotting. ECRG4 expression was weak positive in normal liver cells but was downregulated in HCC cells in vivo or in vitro. A decreased expression of ECRG4 was associated with the age of the patients, metastasis and Ki-67 proliferation index. However, decreased ECRG4 expression was not associated with differentiation, tumor size, the presence of portal vein tumor thrombosis, satellite lesions, tumor relapse or mortality. Further investigations revealed that ectopic expression of ECRG4 inhibited cell proliferation, migration and invasion and promoted cell apoptosis in SMMC-7721 cells, which was mediated by the regulation of BAX and B cell lymphoma-2, in addition to the upregulation of epithelial-mesenchymal transition markers. In conclusion, the results of the present study indicated that ECRG4 was downregulated in HCC and served important roles in promoting cell proliferation and migration.

C2orf40 inhibits hepatocellular carcinoma through interaction with UBR5

“…In this study, both online data and our clinical samples or cell lines showed that C2orf40 was highly expressed in normal tissues (HN) and hypermethylated in HCC. Then, we found that C2orf40 was not only consistent with the results reported earlier 11 but also could induce G0/G1 cell cycle arrest in vitro. On this basis, the results showed that C2orf40 can also significantly inhibit the growth of tumors through the analysis of xenograft tumor model.…”

“…C2orf40, also known as the esophageal cancer‐related gene 4 (ECRG4), is a potential tumor suppressor gene, low‐expressed for promoter methylation in many types of tumors 3–10 . So far, only one paper in PubMed reported that C2orf40 was related to HCC, and the results suggested that C2orf40 may be a potential anticancer target in HCC 11 . However, the precise mechanism is still unclear.…”

Therapeutic effects of tyroserleutide on lung metastasis of human hepatocellular carcinoma SK-HEP-1 and its mechanism affecting ICAM-1 and MMP-2 and -9

“…By using a microplate reader (Thermo Scientific), the OD of each well at a wavelength of 490 nm was detected. 4 The inhibition rate of growth (%)=(1-OD value of drug group/OD value of the control)×100%.…”

ECRG4 Represses Cell Proliferation and Invasiveness via NFIC/OGN/NF-κB Signaling Pathway in Bladder Cancer

“…et al, 2017 ). Although many studies have strongly suggested the role of ECRG4 as a potential tumor suppressor gene, some other reports have also demonstrated the oncogenic role of ECRG4 in patients with papillary thyroid carcinoma ( Chen J. et al, 2015 ) and hepatocellular carcinoma ( Ge et al, 2017 ).…”