Histology and histopathology Vol.36,nº10 (2021)
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- PublicationOpen AccessMitochondrial support and local translation of mitochondrial proteins in synaptic plasticity and function(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Liang, YongTianComplex neural and brain functions are executed through structural and functional alterations of synapses and neurons. Neuronal compartmentalization requires neurons to allocate mitochondria and proteins in a spatiotemporal manner to allow their plasticity, function and homeostasis. Importantly, mitochondria are known to interact with and modulate synaptic activities through their ATP supply, calcium buffering and signaling abilities. Over the years, mitochondrial support and local translation (including mitochondrial proteins) at neuronal sub-compartments and their synaptic specializations have been considered critical for maintaining synaptic plasticity and function. Recently, evidence has shown that late endosomes can serve as sites for local translation of mRNAs crucial for mitochondrial integrity and mitochondrial compartments can fuel plasticity-induced local translation. Indeed, failed mitochondrial homeostasis and subsequent synaptic dysfunction are often intricately linked in the malfunction of the central nervous system in synaptic aging and diseases. In this review, I will discuss the critical role of local translation (including mitochondrial proteins) in dendrites, axons and synapses on neuronal/synaptic plasticity and function.
- PublicationOpen AccessPrognostic significance of E-cadherin, β-catenin and cyclin D1 in oral squamous cell carcinoma: a tissue microarray study(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Al-Rawi, Natheer; Al Ani, Muwaffaq; Quadri, Asif; Hamdoon, Zaid; Awwad, Aktham; Al Kawas, Sausan; Al Nuaim, AhmedObjective. To study the prognostic significance of E-cadherin, β-catenin, and cyclin D1 expression in oral squamous cell carcinoma. Subjects and Methods. The study included 65 subjects with histologically confirmed squamous cell carcinoma. TMA blocks were prepared for immunohistochemical quantification of the expression of the three markers using IHC profiler and Immune ratio plugin of Image J. Results. E-cadherin expression was significantly correlated with histological grades and the metastasis status (p<0.05), whereas β-catenin expression was significantly correlated with smoking and tumor recurrence (P<0.05). Cyclin D1 expression was significantly correlated with depth of invasion and tumor recurrence. (p<0.05). Advanced tumor stage and depth of tumor invasion increases the risk of recurrence or death by 2.5 times (OR=2.53 and 0.84 respectively). Conclusion. High expression of β-catenin and cyclin D1 are significantly correlated with tumor recurrence and old age. Depth of invasion, low histological grade and old age were a significant predictor for the risk of having tumor recurrence and cancer related death.
- PublicationOpen AccessImmunohistological score of transcription factor 21 had a positive correlation with its urinary excretion and proteinuria in immunoglobulin a nephropathy(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Takahashi-Kobayashi, Mayumi; Usui, Joichi; Yaguchi, Misa; Yamazaki, Satoshi; Kawamura, Tetsuya; Kaneko, Shuzo; Seshan, Surya V; Yamagata, KunihiroTranscription factor 21 (TCF21) contributes to mammalian nephrogenesis, and especially to glomerular maturation. Our previous study suggested its influence on glomerular injury, showing that TCF21 expression in podocytes had a positive correlation with the urinary protein value and also with the urinary TCF21 concentration. We now focus on its influence on the clinical course of immunoglobulin A nephropathy (IgAN), as patients with IgAN constitute the largest population of individuals with primary chronic glomerulonephritis in the world. Twenty cases of IgAN were divided into two groups according to the immunohistological score (IHS) of glomerular TCF21 expression: group IHS1 (n=7) and group IHS2+3 (n=13). Sixteen of the 20 cases were followed up for 2 years. Group IHS2+3 had heavier urinary protein (p=0.03) and a greater urinary TCF21 level (p<0.001) compared to group IHS1 at baseline. None of the other factors including hematuria, estimated glomerular filtration rate (eGFR), or the Oxford classification showed a statistically significant difference between these two groups. At the 2-year follow-up, even though the rate of remission in urinary protein, hematuria and the eGFR decline were not statistically correlated to IHS, the IHS2+3 group had a slight tendency toward a steeper eGFR decline compared to IHS1 (p=0.31). The present study suggested that the higher IHS of TCF21 corresponded to heavier proteinuria and a higher urinary TCF21 level in IgAN. This could be the first step in determining the TCF21 value for predicting the prognosis for IgAN.
- PublicationOpen AccessD-2-hydroxyglutarate dehydrogenase in breast carcinoma as a potent prognostic marker associated with proliferation(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Hayashi, Chiaki; Takagi, Kiyoshi; Sato, Ai; Yamaguchi, Mio; Minemura, Hiroyuki; Miki, Yasuhiro; Harada-Shoji, Narumi; Miyashita, Minoru; Sasano, Hironobu; Suzuki, TakashiBackground. D-2-hydroxyglutarate dehydrogenase (D2HGDH) catalyzes D-2-hydroxyglutarate to α-ketoglutarate and is involved in the regulation of cellular energy and biosynthetic intermediates. Previously, D2HGDH was reported to decrease 2-hydroxyglutarate level in breast carcinoma cells, but no other report has examined D2HGDH in breast carcinoma, and its significance remains unknown. Methods. We first immunolocalized D2HGDH in 224 invasive breast carcinomas and evaluated its clinicopathological significance. We next examined associations between gene expression of D2HGDH and α-ketoglutarate-dependent dioxygenases in 23 breast carcinoma tissues using the gene expression profile data. Finally, we examined the effects of D2HGDH on the proliferation in three breast carcinoma cells. Results. D2HGDH immunoreactivity was detected in 49% of invasive breast carcinomas, and the immunohistochemical D2HGDH status was positively associated with histological grade, HER2 and Ki-67, while it was inversely associated with estrogen receptor. Moreover, it was significantly associated with worse prognosis of the breast cancer patients, and it turned out to be an independent prognostic factor for both the disease-free and breast cancer-specific survival in these patients. Gene expression profile data revealed that D2HGDH expression was positively associated with the expression of 6 α-ketoglutarate-dependent dioxygenases (KDM3A, PLOD1, EGLN2, ALKBH1, ASPH and ALKBH7). Consequent in vitro experiments demonstrated that D2HGDH overexpression significantly increased the cell proliferation activity of MCF-7, T47D and MDA-MB-231 cells. Conclusion. These results suggest that D2HGDH plays an important role in the growth of breast carcinoma, possibly through regulating functions of αketoglutarate-dependent dioxygenases, and that D2HGDH status is a potent worse prognostic factor in breast cancer patients
- PublicationOpen AccessLong non-coding RNA-KCNQ1OT1 mediates miR-423-5p/microfibril-associated protein 2 axis in colon adenocarcinoma(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Yin, Xunhai; Jiang, Amín; Ma, Zhibin; Lu, Xi; Li, Dongyue; Chen, YingyingBackgrounds. Long non-coding RNAs (lncRNAs) function as competing endogenous RNAs (ceRNAs) that contribute to carcinogenesis. Herein, we plan to explore whether lncRNA KCNQ1OT1 modulated miR-423-5p/microfibril-associated protein 2 (MFAP2) signaling axis is implicated in the progression of human colon adenocarcinoma. Material and methods. Clinical specimens were collected for histologic examination and gene expression analysis. In vitro experimental measurements, including CCK8, transwell and TUNEL staining, were performed to evaluate cell proliferation, migration and apoptosis. Results. up-regulation of KCNQ1OT1 and MFAP2 and down-regulation of miR-423-5p in COAD tissues were substantiated by The Cancer Genome Atlas (TCGA) database and our clinical specimens. In vitro experimental measurements exhibited that knockdown of KCNQ1OT1 facilitated miR-423-5p expression and inhibited MFAP2 expression, simultaneously. Transfection of si-KCNQ1OT1, miR-423-5p mimics or si-MFAP2 had the ability to repress malignant phenotypes of COAD cells. Intriguingly, overexpression of MFAP2 restrained si-KCNQ1OT1- or miR-423-5p mimics-induced the inhibition of cell proliferation and migration and elevation of the apoptotic proportion of COAD cells. Conclusions. KCNQ1OT1 serves as a molecular sponge of miR-423-5p to accelerate the expression of MFAP2 that may be involved in the development of COAD. Our findings present a novel signaling axis KCNQ1OT1/miR-423-5p/MFAP2, which provides a theoretical basis and therapeutic target for the treatment of COAD.