Fig. 7. SRSF3 expression is altered in human HCC.

(A) Immunohistochemical staining for SRSF3 on human liver cancer tissue microarray. Normal liver shows strong nuclear staining, whereas cirrhotic liver and most HCC samples stain weakly. Representative HCC sections showing positive and negative staining for SRSF3 are shown. Insets show higher magnification of nuclear staining. Melanoma shows very strong SRSF3 staining and is used as positive control. (B) Pathological samples of normal human livers show strong nuclear staining for SRSF3. Carcinoma and adenoma samples show either weak staining or cytoplasmic staining for SRSF3 (arrows). (C) Quantification of SRSF3 nuclear staining from normal liver (Nrml), adenoma (Ade) and HCC tissue (4 fields per section, n=4). Black bars indicate strongly staining nuclei, and gray bars weakly staining nuclei. (D) Analysis of splicing of INSR, FN1 and SLK in human liver cancer cell lines Hep3B, HepG2 and Huh7 compared to WT and HKO livers, and splicing of Fn1 in HepG2 and Huh7 cells following SRSF3 siRNA knockdown. The mean percentage of exon skipping or EDA exon inclusion is given below the gel image. (E) Immunohistochemical staining for EDA-FN on human liver samples compared to HKO tumor. (F) Schematic of how loss of SRSF3 activates multiple pathways causing mitogenesis, steatosis, fibrosis and EMT that eventually cause HCC. Solid lines show activation or increased expression, dotted line indicates loss of expression