Fig 2: let7f-5p expression is negatively correlated with MAPK6 expression in patients with pneumonia. Reverse transcription-quantitative PCR analysis was performed to detect the expression levels of (A) let7f-5p and (B) MAPK6 in the peripheral venous blood of patients with pneumonia and healthy volunteers. (C) Pearson's correlation analysis was performed to determine the correlation between let7f-5p and MAPK6. **P<0.01 vs. healthy volunteers.

Fig 3: Extracellular signal-regulated kinase 3 (ERK3) is reduced in p21-depleted cell lines. (A–C) Microarray analysis. HTR cells were treated with sicon or sip21 #1 for 48 h and the RNA from three independent experiments was extracted. (A) Western blot control of HTR cells with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as loading control. (B) The effects of sip21 #1 on different pathways were determined by gene ontology enrichment analysis using Database for Annotation, Visualization and Integrated Discovery (DAVID) [37]. (C) Heatmap of the most differently expressed genes. Gene expression was analyzed using HumanHT-12 v4 beadchip array (Illumina, San Diego, CA, USA). Genes with a p-value < 0.01, and a fold change greater than 2 (red color code) and below 0.5 (blue color code), respectively, are included. (D) Western Blot of HTR cells treated with control siRNA (sicon) or two distinct siRNA against p21 (sip21 #1 or #2) for 48 h. Ratio of ERK3/GAPDH is shown. GAPDH served as loading control. (E,F) The gene levels of p21 (E) and ERK3 (F) were measured. (G) Western blot analyses of Jar cells treated as in (D). (H,I) The gene levels of p21 (H) and ERK3 (I). (J) Western blot analyses of HeLa cells treated as in (D). (K,L) The gene levels of p21 (K) and ERK3 (L). The mRNA data are based on three experiments and presented as RQ with minimum and maximum range. RQ: relative quantification of gene expression. * p < 0.05, ** p < 0.01, *** p < 0.001.

Fig 4: pcDNA3.1-MAPK6 increases MAPK6 expression. (A) Reverse transcription-quantitative PCR was performed to assess the transfection efficiency of pcDNA3.1-MAPK6 in A549 and WI-38 cells. pcDNA3.1-MAPK6 transfection efficiency in A549 and WI-38 cells was also (B) determined via western blotting and (C) semi-quantified. **P<0.01 vs. pcDNA3.1.

Fig 5: let7f-5p attenuates LPS-induced inflammatory injury by targeting MAPK6. (A) Cell Counting Kit-8 assay was performed to assess cell viability in A549 and WI-38 cells. Reverse transcription-quantitative PCR was performed to determine (B) IL-6 and (C) TNF-a mRNA expression levels in A549 and WI-38 cells. ELISAs were performed to assess the concentrations of (D) IL-6 and (E) TNF-a in the cell culture medium of A549 and WI-38 cells. **P<0.01 and ***P<0.001 vs. Ctrl; &P<0.05 and &&P<0.01 vs. LPS; #P<0.05 and ##P<0.01 vs. LPS + let7f-5p mimic. LPS, lipopolysaccharide; Ctrl, control.