FAT10 promotes invasion and metastasis of hepatocellular carcino-ma through activating RhoA / 中国肿瘤临床

ABSTRACT

Objective:To investigate the correlation of FAT10 expression with the malignant characteristics of hepatocellular car-cinoma (HCC), and to explore the effect of FAT10 on RhoA and cytoskeleton of HCC. Methods: Immunohistochemistry (IHC) was used to detect the FAT10 expression level of 108 HCC patients, and the correlation between the expression of FAT10 and the malignant characteristics of HCC patients was analyzed. We transiently transfected plasmids with overexpressed FAT10 using 7721 and HepG2 cells or interfered with FAT10 expression using siRNA in Huh7 and LM3 cells. Active-RhoA, total-RhoA, and ROCK protein expres-sion levels were detected by Western blot analysis after overexpression or interference. We also used immunofluorescence to detect changes in the cytoskeleton protein F-actin after FAT10 overexpression in 7721 cells. Results:Correlation analysis showed that both ac-tive-RhoA and FAT10 expression levels were significantly correlated with clinical malignant characteristics by using IHC (RhoAme-tastasis, P=0.036 and recurrence, P=0.026;FAT10metastasis, P=0.031 and recurrence P=0.004). In addition, active-RhoA expression level was correlated with FAT10 (P=0.000). Survival analysis showed that the prognoses of low-expression active RhoA (P=0.019) or FAT10 (P=0.026) groups were significantly better than those of the high-expression groups. Western blot analysis showed that FAT10 increased the expression of active-RhoA and ROCK. However, the expression of active-RhoA and ROCK decreased after FAT10 inter-ference. F-actin expression increased in the 7721 cells with overexpressed FAT10 (all P<0.01). Moreover, FAT10 facilitated F-actin ag-gregation on cell membrane and changes in F-actin. Conclusion:FAT10 is correlated with the malignant characteristics of HCC and may promote changes in HCC cytoskeleton induced by active-RhoA.