Oxaliplatin, as a first-line drug, frequently causes chemoresistance in colorectal cancer (CRC). The role of N6-methyladenosine (m6A) modification in multiple biological functions has been well studied. However, the molecular mechanisms underlying m6A methylation in modulating anti-cancer drug resistance in CRC remain obscure. In the present study, we found that YTH m6A RNA-binding protein 3 (YTHDF3) was highly expressed in oxaliplatin-resistant (OXAR) CRC tissues and cells. Moreover, we observed that YTHDF3 could recognize the 5′ untranslated region of significantly m6A-methylated RNAs, which were associated with tumor resistance and recruit eukaryotic translation initiation factor 3 subunit A (eIF3A) to facilitate the translation of these target genes. Furthermore, we determined that eukaryotic translation initiation factor 2 alpha kinase 2 (eIF2AK2) bridged YTHDF3 and eIF3A, enhancing the stability of the YTHDF3/eIF3A complex in OXAR CRC cells. Taken together, our data identified YTHDF3 as a novel hallmark and revealed the molecular mechanism of YTHDF3 on gene translation via coordination with eIF2AK2 in OXAR CRC cells.
The prevalence of CKD is high in the elderly population than that of adult CKD in Shanghai. The most risk factors for elderly CKD patients are similar to the adult population. But hypercholesterolemia as a risk fact of elderly CKD is different from adult CKD.
The present study aimed to investigate the effect of pentraxin 3 (PTX3) on the regulation of proliferation and apoptosis in human glomerular mesangial cells (HMCs). Small interfering (si)RNA was designed and synthesized to inhibit the expression of endogenous PTX3, and the effects on the proliferation and apoptosis of HMCs were detected by flow cytometry and an MTT assay. Western blot analysis was used to detect the activation of mitogen-activated protein kinase (MAPK) proteins in HMCs with PTX3 knockdown. Three siRNAs targeting PTX3 were individually transfected into HMCs for 48 h, and reverse-transcription quantitative PCR demonstrated that the relative mRNA expression of PTX3 was significantly decreased in all groups by up to 79.62% of that in the control group (P<0.05). Following transfection with PTX3-siRNA, the viability of an HMC line was significantly decreased in comparison with that of a control group transfected with scrambled siRNA. However, PTX3-siRNA did not significantly effect early and late apoptotic cell populations in HMCs compared with those in the control. Endogenous PTX3 interference was found to significantly decrease p38 MAPK, extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase phosphorylation. In conclusion, silencing of PTX3, inhibited the proliferation of HMCs via MAPK pathways, but exerted no effect on the apoptosis of HMCs.
The main purpose of this study was to explore treatment effect of hydroxychloroquine-loaded OX7 nanoliposomes in murine systemic lupus erythematosus (SLE) disease model. Modification of OX7 monoclonal antibody conferred hydroxychloroquine-loaded OX7 nanoliposomes targeting to renal
mesangial cells. The SLE mice models were treated with functional nano liposome via tail vein injection, and then the therapeutic effects on lupus nephritis and complicated pneumonia were evaluated. Our research showed that chronic graft versus host disease lupus nephritis mice model has similar
characteristic features of renal pathological damage with human SLE, and is reliable for related study. The symptoms and incidence of pneumonia in model mice were significantly alleviated and reduced after treatment with functional nano liposomes prepared in this experiment.
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