Fig. 6: ARID1A deficiency promotes liver cancer cell metastasis via dysregulation on PMP22 and GSC.

A Immunoblotting on Pmp22 and Gsc in liver tissues of 3 and 14 month old Arid1a^fl/fl mice and Arid1a^LKO littermates. B Representative IHC staining (Left) and quantification of positive staining (Right) for Pmp22 and Gsc in liver tissues of 3-month-old Arid1a^fl/fl mice and Arid1a^LKO littermates. Scale bar = 50 μm. Data are presented as the mean ± SEM (n = 5 per group). *p < 0.05, **p < 0.01, calculated by a two-tailed Student’s t-test. C Representative images of invasive MHCC-97H cells transfected with Pcdh-PMP22 construct; lentiviral shARID1A-1, and ARID1A-knockdown cells co-transfected with Pcdh-PMP22 in transwell assays (Scale bar, 100 µm) (Left) and quantification of the invasive cells (Right). Data are shown as mean ± SEM of three independent experiments. *p < 0.05, **p < 0.01, calculated by a two-tailed Student’s t-test. D Representative images and quantification of the invasive MHCC-97H cells treated with the indicated lentiviral shRNA plasmids for ARID1A (shARID1A-1) and GSC (shGSC-1) in transwell assays. E The relapse-free survival and the overall survival in HCC patients with high or low expression of PMP22 (Left) and GSC (Right), examined by Kaplan-Meier analysis. F Schematic diagram of the dysregulated mechanism related to PMP22 and GSC loci upon ARID1A deficiency. Based on our data, we proposed the working model of the SWI/SNF complex in maintaining chromatin organization mediated by the BRG1-RAD21 axis in hepatocytes. Once ARID1A is deficient, the chromatin loop tethering promoter to the enhancer of Pmp22 might be weakened due to the attenuated anchorage force arising from insufficient BRG1 (Top); the unaided boundaries lead to TAD remodeling surrounding Gsc locus to some extent (Bottom).