LINC01572 promotes the malignant progression of lung adenocarcinoma by modulating p53 mediated by miRNA-338-5p/TTK axis.

OBJECTIVES: Lung cancer is one of the malignant tumors that threaten human health seriously. Long non-coding RNA (lncRNA) is an important factor affecting tumorigenesis and development. However, the mechanism of lncRNA in lung cancer progression remains to be further explored. METHODS: In this study, the TCGA database was analyzed, and LINC01572 was found to be increased in lung adenocarcinoma (LUAD) tissues. Thereafter, with the help of databases including lncBase, TargetScan, and mirDIP, as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, LINC01572/miRNA-338-5p/TTK regulatory axis and downstream p53 signaling pathway were excavated. qRT-PCR was adopted to detect levels of LINC01572, miRNA-338-5p, and TTK in LUAD cells. The role that LINC01572 played in LUAD cells was validated by CCK-8 assay, flow cytometry, colony formation, Transwell, and scratch healing assays. The binding ability between LINC01572/TTK and miRNA-338-5p was then verified by dual-luciferase and RIP analysis. KEY FINDINGS: The results of this study demonstrated that LINC01572 was elevated in LUAD cells compared with normal cells. The overexpression of LINC01572 promoted the proliferative and migratory properties of LUAD cells but inhibited cell apoptosis. The inhibition of LINC01572 resulted in the opposite result. In addition, rescue experiments revealed that LINC01572, as a molecular sponge of miRNA-338-5p, targeted TTK to manipulate p53 for facilitating LUAD cell malignant progression. Apart from this, we constructed a mouse xenograft model and confirmed that the knockdown of LINC01572 hindered the growth of LUAD solid tumors in vivo. CONCLUSIONS: Our findings illuminated the molecular mechanism of LINC01572 influencing LUAD and provided new insights for targeted therapy of LUAD cells.

Downregulation of microRNA-9 reduces inflammatory response and fibroblast proliferation in mice with idiopathic pulmonary fibrosis through the ANO1-mediated TGF-ß-Smad3 pathway.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with increasing occurrence, high death rates and unfavorable treatment regimens. In the current study, we identified the expression of microRNA-9 (miR-9) and anoctamin-1 (ANO1) in IPF mouse models induced by bleomycin, and their effects on inflammation and fibroblast proliferation through the transforming growth factor-ß (TGF-ß)-Smad3 pathway. To verify the targeting relationship between miR-9 and ANO1, we used bioinformatics prediction and conducted a dual-luciferase reporter gene assay. The underlying regulatory mechanisms of miR-9 and the target gene ANO1 were investigated mainly with the treatment of miR-9 mimic, miR-9 inhibitor, or siRNA against ANO1 in fibroblasts isolated from IPF mice. Enzyme-linked immunosorbent assay was performed to investigate the effect of miR-9 or ANO1 on inflammatory factors. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry were used to detect fibroblast proliferation and apoptosis. Reverse transcription quantitative polymerase chain reaction and western blot analysis were applied to measure the expression of the TGF-ß-Smad3 pathway-related genes. The determination of luciferase activity suggested that miR-9 targets ANO1. Upregulation of miR-9 or silencing of ANO1 intensified inflammation in IPF, promoted proliferation and inhibited apoptotic ability of lung fibroblasts. MiR-9 negatively modulated ANO1, and thus activated the TGF-ß-Smad3 pathway. These findings suggest that miR-9 can indirectly activate the TGF-ß-Smad3 pathway by inhibiting the expression of ANO1, thereby aggravating inflammation, promotes proliferation and suppressing apoptosis of lung fibroblasts in mice models of IPF.