Histology and histopathology Vol.39, nº5 (2024)

Ir a Estadísticas

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    WTAP enhances the instability of SYTL1 mRNA caused by YTHDF2 in bladder cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Wang, Jiansong; Luo, Jianjun; Wu, Xuecheng; Li, Zhuo
    Background. Bladder cancer (BCa) is the most frequent type of cancer in humans. The association between m6A modification and the anti-tumor effects of natural killer (NK) cells has been described in BCa. This study intended to investigate the implications of m6A regulators in modulating SYTL1 expression in BCa and the association with the anti-tumor effects of NK cells. Methods. The prognostic role of SYTL1 in BCa was investigated using bioinformatics analysis, and the correlation between SYTL1 expression and NK cells was analyzed. The effects of SYTL1 on the anti-tumor response of NK-92 cells were examined by RT-qPCR, cytotoxicity, western blot, and ELISA assays. The relationships among WTAP, YTHDF2, and SYTL1 were investigated by RT-qPCR, RIP-qPCR, ELISA, and actinomycin D treatment. Finally, the effects of WTAP and SYTL1 on BCa tumor growth and the anti-tumor response of NK cells were verified in vivo. Results. SYTL1 was reduced in BCa tissues and had a prognostic significance, which was related to NK cell-mediated anti-tumor responses. NK-92 cells produced toxicity to BCa cells, which was further enhanced by SYTL1 overexpression in BCa cells through prompting LDH, NKG2D, NKp30, and NKp44 and IFN-γ levels. WTAP enhanced the degradation of the SYTL1 mRNA by YTHDF2. WTAP and YTHDF2 impaired the anti-tumor response of NK cells in BCa. SYTL1 inhibited the BCa progression in mice while enhancing the anti-tumor response of NK cells. Conclusions. WTAP inhibited the anti-tumor response of NK cells to BCa cells by promoting the degradation of SYTL1 mRNA through YTHDF2-mediated m6A methylation.
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    The promoting effects of Grin2d expression in tumorigenesis and the aggressiveness of esophageal cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Wang, Lin Lin; Li, Jun; Xue, Hang; Zhang, Li; Yu, Da yong; Yang, Ning; Yun, Wen jing; Zhao, Ming Zhen; Zheng, Hua Chuan
    Grin2d is an ionotropic NMDA receptor, a subunit of glutamate-dependent, and a facilitator of cellular calcium influx in neuronal tissue. In this study, we found that Grin2d expression was higher in esophageal cancer than in normal mucosa at both the mRNA and protein level using RT-PCR, bioinformatics analysis, and western blotting (p<0.05). Grin2d mRNA expression was positively correlated with old age, white race, heavy weight, distal location, adenocarcinoma, cancer with Barrett’s lesion, or high-grade columnar dysplasia (p<0.05). The differential genes associated with Grin2d mRNA were involved in fat digestion and absorption, cholesterol metabolism, lipid transfer, lipoproteins, synaptic membranes, and ABC transporters (p<0.05). The Grin2d-related genes were classified into the following categories: metabolism of glycerolipids, galactose, and O-glycan, cell adhesion binding, actin binding, cadherin binding, the Hippo signaling pathway, cell-cell junctions, desmosomes, DNA-transcription activator binding, and skin development and differentiation (p<0.05). Grin2d immunoreactivity was positively correlated with distal metastasis and unfavorable overall survival in esophageal cancer (p<0.05). Grin2d overexpression promoted proliferation, migration, and invasion in esophageal cancer cells but blocked apoptosis (p<0.05) and increased the expression of PI3K, Akt and p-mTOR. Grin2d knockout caused the opposite effects. These findings indicated that upregulated Grin2d expression played an important role in esophageal carcinogenesis via the PI3K/Akt/mTOR pathway and might be a biological marker for aggressive tumor behavior and poor prognosis. Its silencing might represent a targeted therapy approach against esophageal cancer.
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    Nasopharyngeal carcinoma with non-squamous phenotype may be a variant of nasopharyngeal squamous cell carcinoma after inhibition of EGFR/PI3K/AKT/mTOR pathway
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Wang, Jiahe; Shang, Yifan; Wang, Yujiao; Li, Ye; Wang, Lei; Huang, Sixia; Lyu, Xinquan
    Nasopharyngeal carcinoma (NPC) is a cancerous tumor that develops in the nasopharynx epithelium and typically has squamous differentiation. The squamous phenotype is evident in immunohisto-chemistry, with diffuse nuclear positivity for p63 and p40. Nonetheless, a few NPCs have been identified by clinicopathological diagnosis that do not exhibit the squamous phenotype; these NPCs are currently referred to as non-squamous immuno-phenotype nasopharyngeal carcinomas (NSNPCs). In a previous work, we have revealed similarities between the histological appearance, etiology, and gene alterations of NSNPC and conventional NPC. According to ultrastructural findings, NSNPC still falls under the category of non-keratinized squamous cell carcinoma that is undifferentiated. NSNPC has an excellent prognosis and a low level of malignancy, according to a retrospective investigation. Based on prior research, we investigated the molecular mechanism of NSNPC not expressing the squamous phenotype and its biological behavior. IHC was used to determine the expression of EGFR, PI3K, AKT, p-AKT, mTOR, p-mTOR, Notch, STAT3 and p-STAT3 in a total of 20 NSNPC tissue samples and 20 classic NPC tissue samples. We obtained human NPC cell lines (CNE-2,5-8F) and used EGFR overexpression plasmid and shRNAs to transfect them. To find out whether mRNA and proteins were expressed in the cells, we used Western blotting and qRT-PCR. Cell biological behavior was discovered using the CCK-8 assay, cell migration assay, and cell invasion assay. EGFR, PI3K, p-AKT and p-mTOR proteins were lowly expressed in NSNPC tissues by immunohistochemistry, compared with classical NPC. In the classical NPC cell lines CNE-2 and 5-8F, overexpression EGFR can up-regulate the expression of p63 through the PI3K/AKT/mTOR pathway, and promote the proliferation, migration, and invasion of nasopharyngeal carcinoma cells. At the same time, knockout of EGFR can down-regulate p63 expression through the PI3K/AKT/mTOR pathway, and inhibit the proliferation, migration, and invasion of nasopharyngeal carcinoma cells. The lack of p63 expression in NSNPC was linked with the inhibition of the EGFR/PI3K/AKT/mTOR pathway, and NSNPC may be a variant of classical NPC.
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    Prognostic value of long noncoding RNA LINC00924 in lung adenocarcinoma and its regulatory effect on tumor progression
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Zhang, Wenlong; Zhao, Yanan; Jia, Yuanyuan; Bai, Yuansong
    Purpose. Long non-coding RNAs (lncRNAs) have been used in the study of tumor biomarkers in recent years. However, the prognostic role of lncRNA LINC00924 (LINC00924) in lung adenocarcinoma (LUAD) has not yet been concluded. Therefore, this study investigates the prognostic value of LINC00924 in LUAD and its regulatory effect on tumor progression. Patients and methods. The LUAD tissues and adjacent normal tissues of 128 subjects were extracted, and the expressions of LINC00924 and miR-196a-5p in tissues and cells were detected by RT-qPCR. The prognostic value of LINC00924 in LUAD patients was obtained by Kaplan-Meier analysis and multivariate Cox regression test. The cell counting kit-8 (CCK-8) and Transwell assay were used to detect the effect of overexpression LINC00924 on LUAD cells. Results. In LUAD tissues and cells, LINC00924 expression was down-regulated and miR-196a-5p expression was up-regulated compared with the normal control group. High expression of LINC00924 inhibited the proliferation level, migration ability and invasion situation of LUAD cells, which was more conducive to the survival and prognosis of LUAD patients. Bioinformatics studies indicated that overexpression of LINC00924 inhibited the development of LUAD by targeting miR-196a-5p, while miR-196a-5p mimic effectively weakened the inhibition.Conclusion. LINC00924 sponges of miR-196a-5p may be considered as a potential prognostic biomarker for LUAD.
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    Up-regulation of Trim28 in pregnancy-induced hypertension is involved in the injury of human umbilical vein endothelial cells through the p38 signaling pathway
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Chen, Min; Shi, Peng; Wang, Ping; Zhang, TingTing; Zhao, Jing; Zhao, Li
    Aims. The present study is to analyze the regulation and potential molecular mechanism of Trim28 on vascular endothelial injury induced by pregnancy-induced hypertension (PIH). Methods. Trim28 mRNA in placental tissues and peripheral blood from PIH patients were determined by quantitative real-time polymerase chain reaction. The serum from PIH was used to stimulate human umbilical vein endothelial cells (HUVECs). After silencing Trim28 in HUVECs, we used CCK-8 assay, Transwell assay and flow cytometry to investigate proliferation, migration and apoptosis. Western blotting was used to measure Trim28 protein level and p38 phosphorylation level. After addition of p38 inhibitor, the proliferation, migration and apoptosis of HUVECs with silenced Trim28 were studied again. Results. Trim28 expression in placental tissues and peripheral blood from PIH patients is elevated, and serum from these patients can up-regulate the expression of Trim28 in HUVECs in vitro. Trim28 silencing significantly inhibits the proliferation and migration of HUVECs by affecting the cell cycle. Down-regulation of Trim28 expression promotes the apoptosis of HUVECs. Trim28 regulates the biological function of HUVECs by affecting the activity of the p38 signaling pathway. Conclusions. The present study demonstrates that Trim28 is up-regulated in peripheral blood of patients with PIH and participates in HUVECs injury through the p38 signaling pathway.