RELA-mediated upregulation of LINC03047 promotes ferroptosis in silica-induced pulmonary fibrosis via SLC39A14.

Long non-coding RNAs play a key role in silicosis, a fatal fibrotic lung disease, and there is an urgent need to develop new treatment targets. Long intergenic non-protein-coding RNA 3047 (LINC03047) is associated with cancer, but its role and mechanism in the progression of silicosis require further elucidation. This study investigated the function of LINC03047 in the epithelial-mesenchymal transition (EMT) during silicosis progression. LINC03047 expression was upregulated in SiO2-treated BEAS-2B and A549 cells, promoting SiO2-induced ferroptosis and subsequent EMT. Moreover, knockdown of LINC03047 significantly decreased the expression of solute carrier family 39 member 14 (SLC39A14), a ferrous iron transporter, and inhibition of SLC39A14 alleviated the ferroptosis and EMT caused by LINC03047 overexpression. We further investigated that NF-κB p65 (RELA) was critical for LINC03047 transcription in SiO2-treated BEAS-2B and A549 cells. In vivo experiments showed that SLC39A14 deficiency improved SiO2-induced lipid peroxidation and EMT. Collectively, our study reveals the function of the RELA/LINC03047/SLC39A14 axis in SiO2-induced ferroptosis and EMT, thereby contributing to the identification of novel drug targets for silicosis therapy.

LncRNA MIR210HG promotes phenotype switching of pulmonary arterial smooth muscle cells through autophagy-dependent ferroptosis pathway.

Hypoxic pulmonary hypertension (HPH) is a pathophysiological syndrome in which pulmonary vascular pressure increases under hypoxic stimulation and there is an urgent need to develop emerging therapies for the treatment of HPH. LncRNA MIR210HG is a long non-coding RNA closely related to hypoxia and has been widely reported in a variety of tumor diseases. But its mechanism in hypoxic pulmonary hypertension is not clear. In this study, we identified for the first time the potential effect of MIR210HG on disease progression in HPH. Furthermore, we investigated the underlying mechanism through which elevated levels of MIR210HG promotes the transition from a contractile phenotype to a synthetic phenotype in PASMCs under hypoxia via activation of autophagy-dependent ferroptosis pathway. While overexpression of HIF-2α in PASMCs under hypoxia significantly reversed the phenotypic changes induced by MIR210HG knockdown. We further investigated the potential positive regulatory relationship between STAT3 and the transcription of MIR210HG in PASMCs under hypoxic conditions. In addition, we established both in vivo and in vitro models of HPH to validate the differential expression of specific markers associated with hypoxia. Our findings suggest a potential mechanism of LncRNA MIR210HG in the progression of HPH and offer potential targets for disease intervention and treatment.

Study on the Effect of Oleic Acid-Induced Lipogenic Differentiation of Skeletal Muscle Satellite Cells in Yanbian Cattle and Related Mechanisms.

Skeletal muscle satellite cells have the ability to differentiate into various cells under different conditions. This study aimed to investigate the effects of different concentrations of oleic acid (50, 100, and 200 µmol/L) on the process of lipogenic transdifferentiation in Yanbian bovine satellite cells, as well as its molecular regulatory mechanism. After inducing differentiation with oleic acid for 96 h, it was observed that the addition of oleic acid resulted in the formation of lipid droplets in the bovine satellite cells, and the triglyceride content showed a dose-dependent relationship with the concentration of OA. qPCR results demonstrated a significant downregulation of myogenesis-related factors (Pax3 and MyoD) and upregulation of lipogenesis-related factors (C/EBP-ß and PPARγ) (p < 0.05). Fatty acid metabolism-related factors, SCD and PLIN2, were also significantly upregulated (p < 0.05). These finding were consistent with the results obtained from Western blotting. Transcriptome sequencing analysis identified 278 differentially expressed genes between the control group and the groups treated with OA. KEGG enrichment analysis showed that differentially expressed genes were mainly concentrated in the adenosine monophosphate-activated protein kinase signaling pathway and fatty acid metabolic pathway. Our study presents that the OA induction of Yanbian bovine skeletal muscle satellite cells can promote cellular lipid transdifferentiation and reveals the potential genes and pathways related to OA induction of these satellite cells.

Fibroblasts and mouse breast cancer cells can form cellular aggregates in improved soft agar culture medium.

We aimed to build cellular aggregates of TS/A and normal fibroblasts (LX-2) or CAFs (ME-iLX-2), verifying the value of this model in the screening of anticancer drugs and demonstrating the effect of CD44 on aggregate formation. We improved soft agar culture medium to coculture CAFs (NFs) and TS/A and compared the amount and area of cellular aggregates. Eugenol was added to this model to test its value. The transcription of human CD44 was analyzed through RT-qPCR. Cellular aggregates were formed, and both the amount and area of aggregates in the TS/A-ME-iLX-2 coculture group were higher than those in other groups. The eugenol inhibited the formation of TS/A-fibroblasts aggregates. Human CD44 was highly transcripted in TS/A-ME-iLX-2 aggregates. Cocultured cellular aggregates of fibroblasts and TS/A were successfully formed in the improved soft agar culture medium, and the promotion effect of CAFs on cancer cells was further confirmed. The eugenol test showed its value in the screening of anticancer drugs. The RT-qPCR results demonstrated the important effect of CD44 on aggregate formation.

Anti­silencing function 1B promotes the progression of pancreatic cancer by activating c­Myc.

The present study aimed to explore the role of histone chaperone anti­silencing function 1B (ASF1B) in pancreatic cancer and the underlying mechanism. The biological function of ASF1B was investigated in pancreatic cancer cell lines (PANC­1 and SW1990) and a mouse xenograft model. Chromatin immunoprecipitation was used to detect the effect of ASF1B on the transcriptional activity of c­Myc. ASF1B was highly expressed in pancreatic adenocarcinoma (PAAD) samples from The Cancer Genome Atlas. ASF1B expression was positively associated with poor survival rates in patients with PAAD. Silencing of ASF1B in PANC­1 and SW1990 cells inhibited cell proliferation, migration and invasion, and induced apoptosis. Mechanistically, ASF1B increased H3K56 acetylation (H3K56ac) in a CREB­binding protein (CBP)­dependent manner. ASF1B promoted H3K56ac at the c­Myc promoter and increased c­Myc expression. In PANC­1 and SW1990 cells, the CBP inhibitor curcumin and the c­Myc inhibitor 10058­F4 reversed the promoting effects of ASF1B on cell proliferation, migration and invasion. In the mouse xenograft model, ASF1B silencing inhibited tumor growth, and was associated with low H3K56ac and c­Myc expression. ASF1B promoted pancreatic cancer progression by activating c­Myc via CBP­mediated H3K56ac.

Hypoxia-induced long non-coding RNA plasmacytoma variant translocation 1 upregulation aggravates pulmonary arterial smooth muscle cell proliferation by regulating autophagy via miR-186/Srf/Ctgf and miR-26b/Ctgf signaling pathways.

BACKGROUND: The lncRNA PVT1 reportedly functions as a competing endogenous RNA (ceRNA) of miR-186 and miR-26b in different tissue types. In this study, we investigated the possible involvement of the miR-186/Srf/Ctgf and miR-26b/Ctgf signaling pathways in the pathogenesis of hypoxia-induced PAH. METHODS: Expression of PVT1, miR-186, miR-26b, and Srf and Ctgf mRNAs were evaluated by real-time polymerase chain reaction. Protein expression of SRF, CTGF, LC3B-I, LC3B-II, and Beclin-I was evaluated using western blotting. The regulatory relationship between the lncRNA, miRNAs, and target mRNAs was explored using luciferase assays. Immunohistochemistry was used to evaluate the expression of SRF and CTGF in situ. MTT assay was performed to assess the proliferation of PASMCs. RESULTS: Exposure to hypoxia markedly altered the expression of PVT1, Srf, Ctgf, miR-186, and miR-26b in a rat model. MiR-186 binding sites in the sequences of Srf mRNA and PVT1 were confirmed by luciferase assays, indicating that miR-186 may interact with both PVT1 and Srf mRNA. Additionally, miR-26b binding sites were identified in the sequences of Ctgf mRNA and PVT1, suggesting that miR-26b may interact with both PVT1 and Ctgf mRNA. In line with this, we found that overexpression of PVT1 reduced expression of miR-26b and miR-186 but activated expression of Srf, Ctgf, LC3B-II, and Beclin-I. CONCLUSIONS: Upregulation of PVT1 by exposure to hypoxia promoted the expression of CTGF, leading to deregulation of autophagy and abnormal proliferation of PASMCs. Dysregulation of the miR-186/Srf/Ctgf and miR-26b/Ctgf signaling pathways may be involved in the pathogenesis of hypoxia-induced PASMCs.

Nanoparticles loaded with circ_0086375 for suppressing the tumorigenesis of pancreatic cancer by targeting the miR-646/SLC4A4 axis.

Nanoparticles possess the ability to adsorb and load other compounds. This study aimed to synthesize a gene carrier with polyethyleneimine (PEI), hyaluronic acid (HA) and mesoporous silica nanoparticles (MSNs) for circ_0086375 delivery to investigate the role and mechanism of circ_0086375 in pancreatic cancer (PC) progression. The expression of genes and proteins was detected by quantitative real-time polymerase chain reaction and Western blot. In vitro experiments were performed by cell counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, transwell assay, and wound healing assay, respectively. Dual-luciferase activity assay was used to investigate the target relationship between miR-646 and circ_0086375 or SLC4A4 (solute carrier family 4 member 4). Circ_0086375 loaded PEI/HA-based mesoporous silica nanoparticles (MSNs) were prepared, and in vivo assay was performed by using xenograft tumor model. Circ_0086375 expression was decreased in PC tissues and cells. Restoration of circ_0086375 suppressed PC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, circ_0086375 acted as a sponge for miR-646 to elevate SLC4A4 expression, which was confirmed to be a target of miR-646. The prepared circ_0086375/MSN/PEI/HA nanocomplexes showed excellent fluorescent properties and a higher cellular uptake of circ_0086375 in PC cells. Moreover, circ_0086375/MSN/PEI/HA showed relatively more anticancer effects in PC than that of circ_0086375 alone in vitro and in vivo. Delivery of circ_0086375 by nanoparticles suppresses the tumorigenicity of pancreatic cancer by miR-646/SLC4A4 axis, suggesting a new potential target for future pancreatic cancer treatment.