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Background Accumulating evidences show that long noncoding RNAs (lncRNA) play essential roles in the development and progression of various malignancies. However, their functions remains poorly understood and many lncRNAs have not been defined in colorectal cancer (CRC). In this study, we investigated the role of DLEU1 in CRC. Methods Quantitative real-time PCR was used to detect the expression of DLEU1 and survival analysis was adopted to explore the association between DLEU1 expression and the prognosis of CRC patients. CRC cells were stably transfected with lentivirus approach and cell proliferation, migration, invasion and cell apoptosis, as well as tumorigenesis in nude mice were performed to assess the effects of DLEU1 in BCa. Biotin-coupled probe pull down assay, RNA immunoprecipitation and Fluorescence in situ hybridization assays were conducted to confirm the relationship between DLEU1 and SMARCA1. Results Here we revealed that DLEU1 was crucial for activation of KPNA3 by recruiting SMARCA1, an essential subunit of the NURF chromatin remodeling complex, in CRC. DLEU1 was indispensible for the deposition of SMARCA1 at the promoter of KPNA3 gene. Increased expression of DLEU1 and KPNA3 was observed in human CRC tissues. And higher expression of DLEU1 or KPNA3 in patients indicates lower survival rate and poorer prognosis. DLEU1 knockdown remarkably inhibited CRC cell proliferation, migration and invasion in vitro and in vivo while overexpressing KPNA3 in the meantime reversed it. Conclusions Our results identify DLEU1 as a key regulator by a novel DLEU1/SMARCA1/KPNA3 axis in CRC development and progression, which may provide a potential biomarker and therapeutic target for the management of CRC.

It has been reported that long non-coding RNA HOXA distal transcript antisense RNA (lncRNA HOTTIP) functions as a tumor promoter in colorectal cancer (CRC). Hence, we paid attention to exploring whether exosomes could carry lncRNA HOTTIP to affect the mitomycin resistance in CRC and to identify the underlying mechanisms. High expression of HOTTIP was detected in mitomycin-resistant CRC cells. Inhibition of HOTTIP reduced the mitomycin resistance. In the co-culture system of mitomycin-resistant cells or their derived exosomes with CRC cells, the HOTTIP was found to be transferred into the parental cells via extracellular vesicles (EVs) secreted from mitomycin-resistant cells and to contribute to the mitomycin resistance. Based on the bioinformatics databases, possible interaction network of HOTTIP, microRNA-214 (miR-214) and Karyopherin subunit alpha 3 (KPNA3) in CRC was predicted, which was further analyzed by dual-luciferase reporter, RNA binding protein immunoprecipitation and RNA pull-down assays. As HOTTIP down-regulated miR-214 to elevate the KPNA3 expression, HOTTIP enhanced the mitomycin resistance through impairing miR-214-dependent inhibition of KPNA3. Finally, HOTTIP was suggested as an independent factor predicting mitomycin response in patients with CRC. Those data together confirmed the promotive effects of EV-carried HOTTIP on the mitomycin resistance, while targeting HOTTIP might be a promising strategy overcoming drug resistance in CRC.

Osteoarthritis (OA) is a common chronic joint disease, the etiology of which is complex. Disturbance to proinflammatory and anti-inflammatory signaling pathways is a major cause of OA. MicroRNAs (miRNAs/miR) are a group of endogenous, short, non-coding RNAs, the expression profile of which is disturbed in the cartilage of patients with OA. To determine the function of miRNAs during the progression of OA, the present study detected the expression levels of nine candidate miRNAs in cartilage samples from 33 patients with OA. The results demonstrated that miR-26a, miR-26b, miR-138 and miR-140 were downregulated in patients with OA. As predicted by a bioinformatics analysis and confirmed by luciferase assay and western blotting, the present study revealed that miR-26a and miR-26b are able to suppress karyopherin subunit alpha 3 (KPNA3) expression by targeting its 3′-untranslated region. Since KPNA3 is an important mediator that modulates nuclear factor (NF)-κB p65 translocation, the present study examined the impact of miR-26a and miR-26b on NF-κB signaling. The results indicated that transfection of cells with a miR-26a or miR-26b inhibitor may promote NF-κB p65 translocation from the cytoplasm to the nucleus via the upregulation of KPNA3. Furthermore, the expression levels of matrix metalloproteinase-3, −9, −13 and cyclooxygenase-2 were upregulated following transfection with a miR-26a or miR-26b inhibitor. These results indicate that downregulation of miR-26a and miR-26b may contribute to the pathogenesis of OA via promotion of the NF-κB signaling pathway. The present study sheds light on the pathogenesis of OA and may provide a target for the development of therapeutic methods for the treatment of OA.

Purpose A potent immunomodulatory role of Vitamin D in both innate and adaptive immunity has recently been appreciated. In allergic asthma, activation of NF-кB induces transcription of various cytokines and chemokines involved in allergic airway inflammation. The nuclear import of activated NF-кB p50/RelA subunit is dependent on importin α3 (KPNA4) and importin α4 (KPNA3). In this study, we examined the role of importin α3 in immunomodulatory effect of calcitriol in human bronchial smooth muscle cells (HBSMCs). Methods Cultured HBSMCs were stimulated with calcitriol in the presence and absence of cytokines, TNF-α, IL-1β, and IL-10. The mRNA transcripts of importin α3 and α4 were analyzed using qPCR while protein expression of importin α3, α4 and nuclear RelA was analyzed by immunoblotting. Results Calcitriol significantly decreased mRNA and protein expression of importin α3 as well as nuclear protein expression of NF-кB p65 (RelA). The decreased activation of RelA by calcitriol was confirmed by decreased release of RelA-inducible molecules, including IL-5, IL-6 and IL-8, by HBSMCs upon calcitriol treatment. Calcitriol attenuated the effect of TNF-α and IL-1β to upregulate mRNA and protein expression of importin α3. IL-10 significantly decreased the TNF-α induced expression of importin α3 and this effect was further potentiated by calcitriol. Conclusions These data suggest that under inflammatory conditions, calcitriol decreases the expression of importin α3 resulting in decreased nuclear import of activated RelA. This could be a novel mechanism by which calcitriol could exert its immunomodulatory effects to reduce allergic airway inflammation and thus may alleviate the symptoms in allergic asthma.