Histology and histopathology Vol.37, nº4 (2022)

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  • Publication
    Open Access
    Knockdown of circular RNA hsa_circ_0062270 suppresses the progression of melanoma via downregulation of CDC45
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Hao, Tian; Yang, Yi; He, Juan; Bai, Jia; Zheng, Yongjian; Luo, Zhanpeng
    Background. Although systemic therapies for melanoma have been improved, the 5-year survival rate of this aggressive cancer remains poor. It has been shown that hsa_circ_0062270 was upregulated in patients with melanoma. However, the relevant mechanism of hsa_circ_0062270 in the progression of melanoma remains unclear. Methods. The CCK-8, EdU staining, flow cytometry, and transwell assays were used to determine the viability, proliferation, apoptosis and invasion in melanoma cells. An in vivo animal study was performed finally. Results. The level of hsa_circ_0062270 was significantly upregulated in melanoma cells. In addition, hsa_circ_0062270 knockdown markedly inhibited the viability, proliferation, invasion and promoted the apoptosis of melanoma cells. Cell division cycle protein 45 (CDC45) is the host gene of hsa_circ_0062270, and downregulation of hsa_circ_0062270 notably decreased the expression of CDC45 in melanoma cells. Rescue assays confirmed that hsa_circ_0062270 regulated the growth of melanoma cells through CDC45. Moreover, immunoprecipitation (RIP) analysis showed that hsa_circ_0062270 interacted with RNA-binding protein (RBP) EIF4A3. Furthermore, in vivo study indicated that knockdown of hsa_circ_0062270 inhibited the melanoma tumor growth in vivo. Conclusions. Downregulation of hsa_circ_0062270 can inhibit the progression of melanoma through downregulation of CDC45. Our findings provide biological mechanisms for the use of hsa_circ_0062270 as a biomarker for melanoma and potential therapeutic target.
  • Publication
    Open Access
    Distal villous lesions are clinically more relevant than proximal large muscular vessel lesions of placental fetal vascular malperfusion
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Stanek, Jerzy
    Background. Fetal vascular malperfusion (FVM) can be diagnosed on placental examination based on histology of distal placental villi and large muscular placental vessels. While histology of both those placental compartments can be low grade or high grade, it is not known if these are clinically equivalent. This retrospective study aimed to compare the impact of placental distal villous and large vessel FVM lesions on clinical and placental phenotypes. Methods. Clinical and placental phenotypes of 479 consecutive ≥20 weeks of gestation at delivery cases of placental FVM were analyzed among 3 groups: Group 1: 86 cases with distal FVM (clusters of sclerotic distal villi and/or those with stromal vascular karyorrhexis and/or mineralization, and/or endothelial fragmentation by CD34 immunostain) without large vessel lesions; Group 2: 186 cases with large vessel lesions (fetal vascular ectasia, vascular thrombi, stem vessel obliteration, intramural fibrin deposition) without distal villous lesions; and Group 3: 207 cases showing both distal villous lesions and large fetal vessel lesions. Results. Statistically significant differences (Bonferroni correction) were observed in: average gestational age at delivery 31, 35, 34 weeks, fetal growth restriction 24, 9, 25%, average placental weight 318, 413, 366 g, postuterine pattern of chronic hypoxic placental injury 12, 2, 6%, luminal vascular abnormalities in stem vessels 16, 3, 11%, and high grade FVM 33, 16, 39%, among Groups 1-3, respectively. Conclusion. Because of longer time needed for its development, distal FVM portends poorer prognosis for the fetus than large vessel FVM
  • Publication
    Open Access
    Environmental enrichment preserves hippocampal neurons in diabetes and stressed rats
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Pamidi, N.; Yap, C.G.; Nayak, S.
    This study evaluated the effect of Environmental Enrichment (EE) on neuron morphology in the CA1, CA3 and dentate hilus (DH) regions of the hippocampus by quantitating the total dendritic arborizations. EE is a potential intervention for stress and diabetes. It is capable of mitigating diabetes and stress-induced cognitive and memory deficit. Diabetes and stress were induced in male Wistar rats (4-5 weeks). Diabetic and stressed rats were exposed to EE on Day 2 post STZ injection and subsequently once daily for 30 days. All animals were sacrificed on Day 30. The hippocampus was dissected and processed for Golgi staining to quantitate dendritic arborizations at the CA1, CA2 and DH regions. Diabetes (D) and Diabetes+stress (D+S) groups had significantly fewer apical and basal dendritic branching points (ADBP, BDBP) at CA1 (p<0.01), CA3 (p<0.001) and DH (p<0.001) relative to control group (NC). Diabetes and stressed rats exposed to EE: [D+EE and D+S+EE groups] exhibited significantly denser ADBP and BDBP at all regions relative to D (p<0.001) and (D+S+EE) (p<0.001) groups respectively. EE significantly preserved neuronal arborizations in hippocampus of diabetic and stressed rats, suggesting a potential entity of diabetes and stress management.
  • Publication
    Open Access
    High miR-3648 expression and low APC2 expression are associated with shorter survival and tumor progression in NSCLC
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Dong, Yongquan; Wu, Biao; Wang, Xiongxiong; Lu, Feijie; Li, Qianjun; Zhao, Qiong
    Background. Emerging studies have demonstrated that microRNAs (miRNAs) play crucial roles in the carcinogenesis of many developing human tumors. However, the clinical significance and biological function of microRNA-3648 (miR-3648) in non-small cell lung cancer (NSCLC) have been largely undefined. Methods. The expression of miR-3648 and the mRNA of adenomatous polyposis coli 2 (APC2) in NSCLC tissues and cell lines were analyzed using quantitative real-time RT-PCR. The prognostic value of miR-3648 and APC2 was examined using the KaplanMeier method and Cox regression analyses. Experiments using NSCLC cells were conducted to explore the influences of miR-3648 on tumor cell proliferation, migration and invasion. Result. Increased expression of miR-3648 was observed in NSCLC tissues and cell lines compared with the corresponding controls (all P<0.05). miR-3648 expression was associated with the differentiation, lymph node metastasis and TNM stage (all P<0.05) of NSCLC patients, and high expression of miR-3648 was associated with poor overall survival rate. NSCLC cell proliferation, migration and invasion were significantly enhanced by miR-3648 overexpression. The further luciferase reporter assay and expression results showed that the decreased APC2 might also be a prognostic biomarker, and served as a target of miR-3648 in NSCLC. Conclusion. The findings from the present study indicate that the overexpression of miR-3648 serves as a useful biomarker for the prediction of prognosis in NSCLC, and promotes tumor cell proliferation, migration and invasion. APC2, as another prognosisrelated molecule, may be a target of miR-3648 in NSCLC.
  • Publication
    Open Access
    Targeting AURKA by microRNA-490-3p suppresses gastric cancer cell growth
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Chen, Rui; Zhou, Shenkang; Fang, Chengfeng; Ye, Feifei; Chen, Jianhui; Jiang, Pinlu
    Objective. To illustrate the molecular mechanism of microRNA-490-3p regulating gastric cancer (GC) cells by targeting AURKA. Methods. Genes with significantly different expression in GC and normal tissue in TCGA-STAD dataset were analyzed by bioinformatics. Expression levels of genes and proteins in GC cells were measured by qRT-PCR and western blot. The interaction between microRNA-490-3p and AURKA was verified by dual luciferase assay. Proliferation, migration, invasion and apoptosis of GC cells were evaluated through a set of cell function assays. Results. MicroRNA-490-3p was significantly less expressed in GC, while AURKA was significantly highly expressed. Dual luciferase reporter gene assay proved that microRNA-490-3p targeted AURKA. Upregulation of microRNA-490-3p restrained proliferation, migration, invasion and stimulated apoptosis of GC cells, which was attenuated by overexpression of AURKA. Conclusions. MicroRNA-490-3p was likely to restrain the development of GC cells by inhibiting AURKA, and it may be an underlying target for GC treatment