Fig 2: MiR-34a-3p attenuated the increase in mPAP and the thickening of the pulmonary arterial walls in APE rats(A) mPAP level was measured in rats. (B) RT-qPCR indicated miR-34a-3p level in pulmonary tissues of rats. (C) H&E staining was used for pathological observation of pulmonary tissues. Blue arrows indicate the pulmonary artery wall, while black arrows indicate the thrombus. (D) RT-qPCR indicated NOR-1 and PCNA levels in pulmonary tissues of rats. ***P<0.001 vs. Sham; ∧P<0.05, ∧∧P<0.01, ∧∧∧P<0.001 vs. APE+scramble. Scramble: negative control. Data are presented as mean ± SD (n=10 in each group).

Fig 3: The negative correlation between LINC00467 and NR4A3 expression in HCC tissues. (A) Expression intensity of NR4A3 detected by probe 207978_s_at in http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6764 dataset which includes 35 HCC tissues and 40 non‐cancerous liver tissues. P < .0001 by Mann‐Whitney test, compared with liver tissues group. (B) Expression intensity of NR4A3 detected by probe 209959_at in http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6764 dataset. P < .0001 by Mann‐Whitney test, compared with liver tissues group. (C) Expression intensity of NR4A3 detected by probe 216979_at in http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6764 dataset. P < .0001 by Mann‐Whitney test, compared with liver tissues group. (D) NR4A3 expression in 56 pairs of HCC tissues and adjacent non‐cancerous liver tissues was measured by qRT‐PCR P < .0001 by Wilcoxon signed‐rank test, compared with liver tissues group. (E) Pearson's correlation analysis revealed NR4A3 expression was negatively correlated with LINC00467 expression in 56 HCC tissues used in D

Fig 4: LINC00467 repressed NR4A3 expression in post‐transcriptional level via Dicer‐dependent RNA splicing. (A) NR4A3 mRNA levels in LINC00467 stably overexpressed, and control SK‐HEP‐1 cells were measured by qRT‐PCR. (B) NR4A3 mRNA levels in LINC00467 stably overexpressed, and control Huh7 cells were measured by qRT‐PCR. (C) NR4A3 mRNA levels in LINC00467 stably depleted, and control SK‐HEP‐1 cells were measured by qRT‐PCR. (D) NR4A3 mRNA levels in LINC00467 stably depleted, and control Huh7 cells were measured by qRT‐PCR. (E) NR4A3 protein levels in LINC00467 stably overexpressed, and control SK‐HEP‐1 cells were measured by Western blot. (F) NR4A3 protein levels in LINC00467 stably depleted, and control Huh7 cells were measured by Western blot. (G) Subcellular distribution of LINC00467 was determined by cytoplasmic and nuclear RNA isolation, followed by qRT‐PCR. (H) Schematic diagram of the predicted interaction region between LINC00467 and NR4A3 mRNA. (I) RNA pull‐down assays with in vitro transcribed LINC00467 was performed to investigate the interaction between LINC00467 and NR4A3 mRNA. (J) After transient transfection of LINC00467 overexpression vectors into SK‐HEP‐1 cells, RIP assays were performed using Dicer‐specific antibody, followed by qRT‐PCR to detect the enrichment of NR4A3 mRNA. (K) After transient transfection of LINC00467 shRNAs into Huh7 cells, RIP assays were performed using Dicer‐specific antibody, followed by qRT‐PCR to detect the enrichment of NR4A3 mRNA. (L) After transient transfection of LINC00467 overexpression vectors into SK‐HEP‐1 cells, the stability of NR4A3 mRNA over time was measured after blocking new RNA transcription with α‐amanitin (50 µmol/L) and normalized to 18S rRNA (a product of RNA polymerase I that is unchanged by α‐amanitin). (M) After transient transfection of LINC00467 shRNAs into Huh7 cells, the stability of NR4A3 mRNA over time was measured after blocking new RNA transcription with α‐amanitin (50 µmol/L) and normalized to 18S rRNA. (N) After transient transfection of Dicer‐specific siRNAs into LINC00467 stably overexpressed SK‐HEP‐1 cells, Dicer and NR4A3 mRNA levels were measured by qRT‐PCR. For A, B, I, J and L, **P < .01, ***P < .001 by Student's t test, compared with vector or beads group. For C, D, K, M and N, **P < .01, ***P < .001, ns, not significant, by one‐way ANOVA followed by Dunnett's multiple comparison test, compared with sh‐NC or siNC+vector group

Fig 5: NR4A3 plays tumour‐suppressive roles in HCC cell proliferation, apoptosis and migration. (A) Overexpression efficiency of NR4A3 in Huh7 cells was verified by Western blot. (B) Glo cell viability assay showed that overexpression of NR4A3 slowed down cell proliferation. (C) BrdU staining assay showed that overexpression of NR4A3 reduced the proliferative cell number. Scale bar, 100 μm. (D) Annexin V‐PI staining and flow cytometric analyses showed that overexpression of NR4A3 increased apoptotic cell number. (E) Transwell migration assay showed that overexpression of NR4A3 repressed cell migration. Scale bar, 100 μm. (F) Knockdown efficiency of NR4A3 in SK‐HEP‐1 cells was verified by Western blot. (G) Glo cell viability assay showed that knockdown of NR4A3 accelerated cell proliferation. (H) BrdU staining assay showed that knockdown of NR4A3 increased the proliferative cell number. Scale bar, 100 μm. (I) Annexin V‐PI staining and flow cytometric analyses showed that knockdown of NR4A3 decreased apoptotic cell number. (J) Transwell migration assay showed that knockdown of NR4A3 promoted cell migration. Scale bar, 100 μm. *P < .05, **P < .01, ***P < .001 by Student's t test, compared with vector group or sh‐NC group