Here we found that levels of miR-23a were decreased in prostate cancer cell lines and tumor tissues. These low levels were associated with poor patients' prognosis. MiR-23a inhibited migration and invasion of prostate cancer in vivo and in orthotopic prostate cancer mice model. MiR-23a decreased levels of p21-activated kinase 6 (PAK6). Expression of miR-23a inhibited phosphorylation of LIM kinase 1 (LIMK1) and cofilin, in turn suppressing formation of stress fibers and actin filaments, which was required for cell motility and invasion. PAK6 bound to LIMK1 and activated it via phosphorylation at Thr-508. Also, PAK6 and LIMK1 were colocalized in the cytoplasma. Thus, miR-23a regulated cytoskeleton by affecting LIMK1 and cofilin. In summary, we have identified the miR-23a-PAK6-LIMK1 pathway of prostate cancer metastasis. Potential therapeutic approach by targeting miR-23 is suggested.

Circular RNA (circRNA) is a class of newly discovered endogenous non-coding RNA with closed circular structure. Some circRNAs have been reported to be closely associated with acute lung injury (ALI). While the expression profile of circRNAs in lipopolysaccharide (LPS)-induced ALI and the underlying roles are still not completely clear. The LPS-induced ALI model of MRC-5 cells was first established, and the expression profiles of circRNAs and mRNAs in LPS-induced MRC-5 cells were confirmed through RNA sequencing analysis. Gene Ontologyanalysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were also applied to predict the latent functions and pathways of the differential mRNAs. After hsa_circ_0059930 knockdown, the proliferation and apoptosis of MRC-5 cells were identified by CCK-8, flow cytometer, and western blot assays. And we predicted the network analysis of hsa_circ_0059930. We testified that LPS could markedly prevent proliferation and induce apoptosis of MRC-5 cells. We discovered a total of 820 differential circRNAs (560 upregulated and 260 downregulated circRNAs) and 484 differential mRNAs (240 upregulated and 244 downregulated mRNAs) in LPS-induced MRC-5 cells. Besides, hsa_circ_0059930 was identified to be significantly upregulated in LPS-induced MRC-5 cells, and knockdown of hsa_circ-0059930 could notably accelerate proliferation and suppress apoptosis of LPS-mediated MRC-5 cells. Moreover, through the network analysis of hsa_circ_0059930, we preliminarily screened the potential regulatory axis hsa_circ_0059930/hsa-miR-382-5p/ Topoisomerase 1 (TOP1) in LPS-induced ALI. Our data contribute to understand the importance of circRNAs and mRNAs in LPS-induced ALI. We also provided many hsa_-circ_0059930-mediated microRNA (miRNA)-mRNA axis, especially hsa_circ_0059930/hsa-miR -382-5p/TOP1 in LPS-induced ALI.

Acute lung injury caused by smoke inhalation is a common severe clinical syndrome. This study aimed to investigate the potential expression of circular RNAs during acute lung injury triggered by smoke inhalation. The acute lung injury rat model was established with smoke inhalation from a self-made smoke generator. The occurrence of acute lung injury was validated by an analysis of the bronchoalveolar lavage fluid and hematoxylin-eosin (HE) staining of lung tissues. Next-generation sequencing and quantitative PCR were performed to identify the differentially expressed circular RNAs associated with acute lung injury that was caused by smoke inhalation. The circular form of the identified RNAs was finally verified by multiple RT-PCR-based assays. The bronchoalveolar lavage fluid (BALF) and lung tissue analysis showed that smoke inhalation successfully induced acute injury in rats, as evidenced by the significantly altered cell numbers, including macrophages, neutrophils, and red blood cells, disrupted cell lining, and increased levels of interleukin-1β, tumor necrosis factor-alpha, and IL-8 in lung tissues. Ten significantly differentially expressed circular RNAs were identified with next-generation sequencing and RT-PCR. The circular form of these RNAs was verified by multiple RT-PCR-based assays. In conclusion, the identified circular RNAs were prevalently and differentially expressed in rat lungs after acute lung injury caused by smoke inhalation.

Background Sepsis is a systemic inflammatory response that can lead to the dysfunction of many organs. The aberrant expression of miRNAs is associated with the pathogenesis of sepsis. However, the biological functions of miR-128-3p in sepsis remain largely unknown, and its mechanism should be further investigated. This study aimed to determine the regulatory network of miR-128-3p and TGFBR2 in lipopolysaccharide (LPS)-induced sepsis. Methods The expression levels of miR-128-3p and transforming growth factor beta receptors II (TGFBR2) were detected by quantitative polymerase chain reaction (qPCR). The protein levels of TGFBR2, Bcl-2, Bax, cleaved caspase 3, Smad2, and Smad3 were measured by western blot. Cell apoptosis was analyzed by flow cytometry. Cytokine production was detected by enzyme-linked immunosorbent assay (ELISA). The binding sites of miR-128-3p and TGFBR2 were predicted by Targetscan online software and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results The level of miR-128-3p was decreased, and TGFBR2 expression was increased in serum samples of sepsis patients and LPS-induced HK2 cells. Overexpression of miR-128-3p or knockdown of TGFBR2 ameliorated LPS-induced inflammation and apoptosis. Moreover, TGFBR2 was a direct target of miR-128-3p, and its overexpression reversed the inhibitory effects of miR-128-3p overexpression on inflammation and apoptosis in LPS-induced HK2 cells. Besides, overexpression of miR-128-3p downregulated TGFBR2 to suppress the activation of the Smad signaling pathway. Conclusion miR-128-3p could inhibit apoptosis and inflammation by targeting TGFBR2 in LPS-induced HK2 cells, which might provide therapeutic strategy for the treatment of sepsis.