Fig 2: The suppressed BM of NSCLC and attenuated SPHK2/S1P/STAT3 pathway in xenograft and zebrafish model by RPTOR blockade. A-J PC-9 cells were injected intravenously to construct the BM mouse model. Fluorescence microscopy showed that RPTOR blockade significantly suppressed the BM formation, the fluorescence of tumor cells in the ROI of BM, the expression of the proliferation marker Ki67 and MVD in the peritumoral area, prolonging overall survival (200 × magnification, scale bar = 50 μm). RPTOR overexpression produced the opposite effects. K Effects of RPTOR expression on the expression of proteins in BM tissue samples in nude mice. RPTOR knockdown reduced the expressions of RPTOR, YY1, SPHK2, and S1P1, with RPTOR overexpression yielding the opposite effects (200 × magnification, scale bar = 50 μm). L-O H1299 and PC9 cells bearing vectors for RPTOR knockdown or overexpression were injected into the perivitelline space of zebrafish embryos. The number of cancer cells at days 1 and 3 after the injection was significantly higher in the RPTOR-overexpressed group than in their respective control groups, whereas the number of cancer cells at days 1 and 3 after injection was significantly lower in RPTOR-knockdown cells than in control cells

Fig 3: CircFAM188A modulates cellular proliferation, invasiveness and autophagy through the miR‐670‐3p/YY1 axis. (A)–(C) EdU and Transwell assays were used to assessing proliferation and invasion, respectively, in all groups (group 1, SKOV3‐LV2‐NC; group 2, SKOV3‐LV2‐1; group 3, SKOV3‐LV2‐1+ miR‐670‐3P inhibitor‐NC; group 4, SKOV3‐LV2‐1+ miR‐670‐3P inhibitor; group 5, SKOV3‐LV2‐1 + PCMV5‐YY1); Error bars indicate standard error; *p < 0.05. (D)–(F) EdU and Transwell assays were used for assessing proliferation and invasion, respectively, in all groups (group 1, A2780‐LV6‐NC; group 2, A2780‐LV6; group 3, A2780‐LV6+ miR‐670‐3P mimics‐NC; group 4, A2780‐LV6+ miR‐670‐3P mimics; group 5, A2780‐LV6 + si‐YY1). Error bars indicate standard error; *p < 0.05. (G) Western blots showing LC3I/II expression in each trial (trial 1, A2780‐LV6‐NC; trial 2, A2780‐LV6; trial 3, A2780‐LV6+ miR‐670‐3P mimic‐NC; trial 4, A2780‐LV6+ miR‐670‐3P mimics; trial 5, A2780‐LV6 + si‐YY1; trial 6, A2780‐LV6 + si‐AYG5); (H) Western blots showing LC3I/II expression in each trial (trial 1, SKOV3‐LV2‐NC; trial 2, SKOV3‐LV2‐1; trial 3, SKOV3‐LV2‐1+ miR‐670‐3P inhibitor‐NC; trial 4, SKOV3‐LV2‐1+ miR‐670‐3P inhibitor; trial 5, SKOV3‐LV2‐1 + PCMV5‐YY1; trial 6, SKOV3‐LV2‐1 + PCMV5‐ATG5).

Fig 4: Schematic diagram of linc00152 and NF‐κB pathway feedback loop promotes RAFLS inflammation via regulating miR‐103a/TAK1 axis and YY1 expression. NF‐κB, nuclear factor‐κB; RAFLS, rheumatoid arthritis fibroblast‐like synoviocytes

Fig 5: YY1 regulated the downstream target gene KTN1 in a DDX3X‐dependent manner in BCa. (A) Chromatographic analysis of the proteins immunoprecipitated using anti‐YY1 antibodies or control IgG antibodies. (B) Black arrows indicate the DDX3X peptide peaks in the YY1‐pulldown samples from MDA‐MB‐231 and BT549 cells compared with those from control IgG samples. (C) Western blotting and co‐immunoprecipitation assays analysis of co‐factors of YY1. (D) Immunofluorescence chemistry assay analysis of the co‐location and co‐expression in both BCa cell lines. (E) The correlation analysis between DDX3X and YY1 expression from the GEPIA database (R = 0.52, P = 3.3e−95), and the correlation analysis between DDX3X and KTN1 expression from the GEPIA database (R = 0.47, P = 4.6e−76). (F) Activity of a reporter containing four canonical YY1‐binding sites and binding of YY1 to the KTN1 promoter in MDA‐MB‐231, BT549, and 293T cells transfected with the KTN1 promoter reporter, the full‐length DDX3X plasmid, and the full‐length YY1 plasmid (n = 4) as determined by a dual‐luciferase assays. (G) ChIP‐qPCR analysis showing the binding enrichment of YY1 at the binding sites on the promoter region of KTN1 detected after knockdown of DDX3X. Error bars are showed with the s.d., n ≥ 3. *P < 0.05, **P < 0.01, and ***P < 0.001. A two‐tailed t‐test or ANOVA was used to assess the P‐values