Epidermal growth factor‐containing fibulin‐like extracellular matrix protein 1 ( EFEMP 1) suppressed the growth of hepatocellular carcinoma cells by promoting Semaphorin 3B( SEMA 3B)

Aim Epidermal growth factor‐containing fibulin‐like extracellular matrix protein 1( EFEMP 1) has been found to be involved in the occurrence and development of many cancers. The relationship between EFEMP 1 and the development of hepatocellular carcinoma ( HCC ) and the molecular mechanism are not fully understood. Methods Real‐time polymerase chain reaction (PCR) and tissue microarray were used to detect the expression of EFEMP 1 in HCC cell lines and tissue. Methylation‐specific PCR assay was used to measure the methylation level of EFEMP 1 in HCC cell lines and tissue. To study the function of EFEMP 1 on cell function, Huh7 and HepG2 were infected with lentiviral particles expressing EFEMP 1. MTT assay and colony formation assay were used to examine the effect of EFEMP 1 on cell proliferation. Annexin‐ VAPC /7‐ AAD double were used to detect the effect of EFEMP 1 on cell apoptosis. To further detect the effect of EFEMP 1 on the development of HCC in vivo, we performed the tumor formation experiment in nude mice. Gene chip was used to detect the expression profile of Huh7 and HepG2 overexpressing EFEMP 1. To further screen out the differences, GO analysis and pathway analysis were performed. To study the effects of SEMA 3B, specific si RNA was used to inhibit the expression of SEMA 3B. Chi‐squared test and rank sum test were used to analyze the relationship between EFEMP 1 expression and HCC clinical characteristic. Results The study found that the expression of EFEMP 1 was significantly decreased in HCC cell lines and HCC tissues. The expression level of EFEMP 1 was related to the TNM (the extent of the tumor, the extent of spread to the lymph nodes, the presence of metastasis) stage and the prognosis of patients with HCC . The decrease of protein expression suggested that the patient prognosis was worse, and the protein level of EFEMP 1 may be an independent factor in the prognosis of HCC patients. Promoter methylation may be one of the reasons for EFEMP 1 inhibition. EFEMP 1 could inhibit the proliferation of HCC cells and promoted the apoptosis of HCC cells to regulate the development of HCC . And EFEMP 1 promoted the apoptosis of HCC cells mainly through the mitochondrial apoptosis pathway. EFEMP 1 may inhibit the proliferation of HCC cells through the SEMA 3B gene in the Axon guidance pathway. Conclusion In summary, our research revealed the regulation of EFEMP 1 on cell proliferation and apoptosis in HCC . EFEMP 1 may suppress the growth of HCC cells by promoting SEMA 3B.