Fig 1: MALAT1 regulated MDM4 level by targeting miR‐185‐5p. (A) The binding sites between MALAT1 and miR‐185‐5p were predicted by starBase v2.0. (B) The complementary sequence between miR‐185‐5p and MDM4 was forecasted by TargetScan Human 7.2. (C) The enrichment of miR‐185‐5p in A549 and H460 cells transduced with si‐MALAT1, MALAT1, or corresponding negative control was assessed. (D and E) The relationship between miR‐185‐5p and MALAT1 or MDM4 was corroborated by dual‐luciferase reporter assay. (F) The expression of MDM4 at the protein level in A549 and H460 cells introduced with si‐MALAT1, anti‐miR‐185‐5p + si‐MALAT1, or corresponding negative control was measured by western blot. *p < 0.05
Fig 2: Knockdown of MDM4 impeded cell malignant behaviors in NSCLC cells. (A and B) The relative MDM4 mRNA and protein expressions in BEAS‐2B, A549, and H460 cells were checked by qRT‐PCR or western blot. (C–G) A549 and H460 cells were transduced with si‐MDM4 or si‐NC. (C and D) The knockdown efficiency of MDM4 was verified by qRT‐PCR and western blot. (E) The proliferation was explored by MTT assay. (F) The apoptosis was appraised by flow cytometry. (G and H) The migratory and invasive capacities were tested by transwell assay. *p < 0.05
Fig 3: The expression of MALAT1 and MDM4 was raised in NSCLC tissues. (A and B) The relative expression of MALAT1 and MDM4 mRNA was detected by qRT‐PCR in 30 paired NSCLC tumor tissues and corresponding normal tissues. (C) The interaction between MALAT1 and MDM4 in tumor tissues was attested by spearman's correlation analysis. (D) The enrichment of MDM4 protein was also certified in tumor tissues and adjacent normal tissues by western blot.*p < 0.05
Fig 4: MALAT1 modulated MDM4 expression in NSCLC cells. (A and B) The overexpression efficiency of MDM4 was demonstrated. (C–F) A549 and H460 cells were introduced with si‐NC, si‐MALAT1, si‐MALAT1+pcDNA, or si‐MALAT1+ MDM4. (C) The proliferation was tested by MTT assay. (D) The apoptosis was checked by flow cytometry. (E and F) The migratory and invasive abilities were examined by transwell assay. (G and H) The expression of MDM4 was explored after MALAT1 knockdown or overexpression in A549 and H460 cells via qRT‐PCR and western blot, correspondingly. *p < 0.05
Fig 5: MALAT1 silence impeded tumor growth in vivo. A549 cells (2 × 106/0.2 ml PBS) stably infected with sh‐MALAT1 or sh‐NC were subcutaneously inoculated into the nude mice. (A) The tumor images were taken. (B) After 7 days implantation, tumor volume measurement was conducted every 4 days. (C) Xenograft tissues were weighted and the average weight was calculated. (D) The levels of MALAT1, miR‐185‐5p, and MDM4 in tumor tissues were examined by qRT‐PCR. (E) The protein expression of MDM4 in tumor tissues was inspected by western blot. *p < 0.05
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