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Increasing evidence suggests that long noncoding RNAs (lncRNAs) are pivotal regulators in oncogenesis. However, the role of numerous lncRNAs has never been unmasked in clear cell renal cell carcinoma (ccRCC). Presently, we investigated the function of long intergenic nonprotein coding RNA 1426 (LINC01426) in ccRCC, as The Cancer Genome Atlas data indicated that LINC01426 was highly expressed in ccRCC tissues and its overexpression was correlated with disappointing prognosis. First, we verified that LINC01426 was indeed upregulated in ccRCC cell lines and its depletion restrained ccRCC cell proliferation and migration. Besides, we proved that LINC01426 facilitated ccRCC tumorigenesis via forkhead box M1 (FOXM1). Moreover, it was revealed that miR‐423‐5p was downregulated and directly targeted FOXM1 in ccRCC, and that LINC01426 positively regulated FOXM1 via its inhibition on miR‐423‐5p. Notably, we also uncovered that miR‐423‐5p was transcriptionally silenced by CTBP1 and HDAC2. Of importance, LINC01426 was certified to distribute both in the cytoplasm and the nucleus of ccRCC cells, and it increased CTBP1 expression through recruiting insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) in cytoplasm whereas interacted with CTBP1 protein to improve the transcriptional repression on miR‐423‐5p in nucleus. Jointly, our observations unveiled that LINC01426 aggravates ccRCC progression via IGF2BP1/CTBP1/HDAC2/miR‐423‐5p/FOXM1 axis, highlighting LINC01426 as a novel promising target for ccRCC treatment. [ABSTRACT FROM AUTHOR]

Radiation‐induced pulmonary fibrosis (RIPF) is a life‐threatening complication of thoracic radiotherapy, which contributes to continued deterioration in pulmonary function. Sphingosine‐1 phosphate receptor 3 (S1PR3) has been identified as a crucial molecule in fibrosis. Accumulating evidence indicated that the inhibition of the S1PRs ameliorates fibrogenesis. Thus, this study aims to explore whether S1PR3 participates in RIPF and elucidates the molecular mechanisms underlying S1PR3‐modulated epithelial–mesenchymal transition (EMT) in transforming growth factor‐β1‐induced pulmonary epithelia. A recombinant adeno‐associated viral‐mediated S1PR3 (AAV‐S1PR3) gene therapy analyzed the effect of S1PR3 gene deficiency on the altered histology structure and molecular mechanisms in the lung of mice with whole‐lung irradiation. Compared with the AAV‐negative control mice, AAV‐mediated S1PR3 knockdown in the lung of mice attenuated pulmonary fibrosis induced by the radiation, as indicated by the alleviation of collagen accumulation, lessened histopathological alterations, and the suppression of inflammatory cells infiltration. S1PR3 deficiency reversed the RIPF concomitantly with abrogated EMT‐related protein (α‐smooth muscle actin). Consistently, S1PR3‐deficient pulmonary epithelia inhibited the EMT process changes and fibrosis formation. Furthermore, S1PR3 was designated as one of the target genes for microRNA‐495‐3p (miR‐495‐3p). The inhibition of miR‐495‐3p promoted the expression of S1PR3 in pulmonary epithelia, whereas the overexpression of miR‐495‐3p inhibited the S1PR3/SMAD2/3 pathway and suppressed the EMT process. Collectively, miR‐495‐3p might be a negative regulator of the EMT process in fibrosis formation by inhibiting the targeted S1PR3 gene. These results established a link between the S1PR3 gene, the EMT process, and the fibrosis, suggesting the pharmacological blockage of S1PR3 as a potential therapeutic strategy for RIPF. [ABSTRACT FROM AUTHOR]