Histology and histopathology Vol.38, nº1 (2023)

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https://hdl.handle.net/10201/128306

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Open Access
Long non-coding RNA XIST promotes the malignant features of oral squamous cell carcinoma (OSCC) cells through regulating miR-133a-5p/VEGFB
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wu, Kankui; Wu, Mengxuan; Wu, Wancui; Liu, Wenzhe
Objective. Oral squamous cell carcinoma (OSCC) represents a frequently seen oral cavity malignancy, and the mechanisms of its occurrence and development remain unclear. The present work examined the expression and biological function of long non-coding RNA (lncNRA) XIST (X-inactive specific transcript) in OSCC cells and tissues. Study design. A total number of 50 OSCC and paired non-carcinoma tissue samples were collected in this study. Gene expression levels in cancer tissues and cells were quantified by RT-qPCR. In addition, gain- and loss-of-function experiments were conducted to investigate the biological roles of XIST as well as its downstream targets in OSCC cells. Results. XIST was upregulated in OSCC cells and tissues, which predicted a poorer prognostic outcome in OSCC patients. Silencing XIST inhibited the growth and invasion of OSCC cells and triggered apoptosis. miR133a-5p was identified as a downstream target of XIST, which was downregulated in OSCC tissues. miR-133a5p mediated the effect of XIST by targeting VEGFB. VEGFB overexpression rescued the inhibitory effects of XIST silencing on cell growth, invasion and migration. Conclusion. Taken together, the above data indicates that XIST serves as an oncogenic factor to enhance the growth and invasion of
Open Access
Neurotoxins and pore forming toxins in sea anemones: Potential candidates for new drug development
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wang, Zhi-Lin; Zhang, Shu-Yi; Hao, Shuang Li; Yang, Wan Xi
There are two kinds of toxins in sea anemones: neurotoxins and pore forming toxins. As a representative of the sodium channel toxin, the neurotoxin ATX II in neurotoxin mainly affects the process of action potential and the release of transmitter to affect the inactivation of the sodium channel. As the representatives of potassium channel toxins, BgK and ShK mainly affect the potassium channel current. EqTx and Sticholysins are representative of pore forming toxins, which can form specific ion channels in cell membranes and change the concentration of internal and external ions, eventually causing hemolytic effects. Based on the above mechanism, toxins such as ATX II can also cause toxic effects in tissues and organs such as heart, lung and muscle. As an applied aspect it was shown that sea anemone toxins often have strong toxic effects on tumor cells, induce cancer cells to enter the pathway of apoptosis, and can also bind to monoclonal antibodies or directly inhibit relevant channels for the treatment of autoimmune diseases.
Open Access
Knockdown of circ_0004585 enhances the chemosensitivity of colorectal cancer cells to 5-fluorouracil via the miR-874-3p/CCND1 axis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wang, Shijie; Cao, Juan; Pei, Lijuan
Background. Colorectal cancer (CRC) is a serious threat to human health and is drug-resistant. Circular RNA _0004585 (circ_0004585) has been shown to be expressed in CRC, but whether it plays a role in CRC with chemoresistance remains unknown. Therefore, this study aimed to investigate the potential role of circ_0004585 in CRC with 5-fluorouracil (5-FU) resistance. Methods. The expression of related genes was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the protein expressions of cleaved caspase-3, cleaved caspase-9, and cyclin D1 (CCND1) were detected by western blot. Cell functions were identified using CCK-8, colony formation, flow cytometry, tube formation and transwell assays. The putative relationships between miR-874-3p and circ_0004585 or CCND1 were validated by dualluciferase reporter assays. Animal experiments were conducted to verify the effect of circ_0004585 on 5-FU resistance in vivo. Results. Circ_0004585 was highly expressed in CRC tissues and cells, particularly in 5-FU-resistant CRC tissues and cells. Circ_0004585 knockdown enhanced 5- FU sensitivity to further inhibit CRC cell viability, colony formation, cell migration and invasion, and accelerate cell apoptosis. MiR-874-3p was the target of circ_0004585, and miR-874-3p depletion partially recovered the malignant behaviors of 5-FU-resistant CRC cells that were blocked by silencing of circ_0004585. In addition, CCND1 was the target of miR-874-3p, and overexpression of CCND1 was able to restore the malignant effects of 5-FU-resistant CRC cells that were repressed by miR-874-3p enrichment. Animal experiments confirmed that circ_0004585 knockdown inhibited the growth of CRC tumors and enhanced 5-FU sensitivity in vivo. Conclusion. Circ_0004585 promotes the development of CRC and increases 5-FU resistance in CRC through the miR-874-3p/CCND1 axis. These results suggest that circ_0004585 may be a therapeutic target for 5-FU-ressitant CRC.
Open Access
High grade acinic cell carcinoma of the breast with clear cytoplasm mimics clear cell carcinoma in a BRCA1 mutation carrier: a case report and review of the literature on the molecular analysis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Min, Liu; Qiao, Huang; Hongkai, Zhang
Acinic cell carcinoma of the breast is an extremely rare tumor. To the best of our knowledge, only one case is reported to have bilateral tumors and had both BRCA1 and TP53 mutation. Herein, we report another case of acinic cell carcinoma of the breast in a 29-years-old female carrying germline BRCA1 and TP53 mutation, and the tumor showed a complex combination of histological features which had not only the reported common features such as diffuse infiltrative small acinar or glandular structures mixed with solid nests, but also the uncommon widespread clear cells, high grade tumor cells. The immunohistochemical profile of the tumor cells was strongly positive for lysozyme and triple negative for ER, PR, HER2. Although she had bilateral high grade breast cancers, this patient refused postoperative adjuvant therapy this time and has been doing well in the past 12 months. As a rare form of triple-negative breast cancer with a relatively not so bad prognosis, more reports are needed to understand its biological characteristics.
Open Access
Circ_0067717 promotes colorectal cancer cell growth, invasion and glutamine metabolism by serving as a miR-497-5p sponge to upregulate SLC7A5
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Song, Mo Song; Liu, Jipan
Open Access
GLUT-1 expression is helpful to distinguish myxofibrosarcoma from nodular fasciitis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Nakayama, Shizuhide; Nishio, Jun; Aoki, Mikiko; Koga, Kaori; Nabeshima, Kazuki; Yamamoto, Takuaki
Myxofibrosarcoma (MFS) is a fibroblastic/ myofibroblastic neoplasm with a variably myxoid stroma. Histologically, MFS shows a wide spectrum of cellularity, pleomorphism and proliferative activity. Because of its variable morphology and lack of discriminatory markers, MFS can be difficult to distinguish from some benign soft-tissue tumors, especially nodular fasciitis (NF). Glucose transporter 1 (GLUT-1) is expressed in a variety of malignant mesenchymal tumors. In the current study, we evaluated GLUT-1 expression to determine its value in distinguishing MFS from NF. Tissue specimens from 14 MFS cases and 16 NF cases were sectioned and stained for GLUT-1 using immunohistochemistry. The percentage of GLUT-1-positive cells was scored as follows: 0 (no staining), 1+ (1-19%), 2+ (20-50%) and 3+ (>50%). Samples with a score of 1+ were defined as GLUT1-expressing samples. GLUT-1 expression was seen in all 14 MFS cases, whereas only 6 NF cases (37.5%) were positive for GLUT-1 and were scored 1+. Notably, 2-3+ GLUT-1 expression was found in 86% of MFS cases and 0% of NF cases. Our results indicate that GLUT-1 is a highly sensitive immunohistochemical marker for MFS and may be useful for the differential diagnosis of MFS and NF.
Open Access
Intussusceptive angiogenesis facilitated by microthrombosis has an important example in angiolipoma. An ultrastructural and immunohistochemical study
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Díaz Flores, Lucio; Gutiérrez, Ricardo; Pino García, Maria; González Gómez, Miriam; Díaz Flores Jr, Lucio; Carrasco, Jose Luis; Madrid, Juan Francisco; Álvarez Argüelles, Hugo
The microvasculature of angiolipoma frequently presents thrombi. Our objectives are to assess whether intussusceptive angiogenesis (IA) participates in vasculature formation in non-infiltrating angiolipoma and, if so, to explore how thrombi are involved in the IA process. For this purpose, we studied angiolipoma specimens (n: 52), using immunohistochemistry, and confocal and electron microscopy. The results showed the presence of folds and pillars, hallmarks of IA, dividing the vessel lumen. Folds showed a cover formed by reoriented endothelial cells from the vessel wall, or from newly formed folds, and a core initially formed by thrombus fragments (clot components as transitional core), which was replaced by extracellular matrix and invaginating pericytes establishing numerous peg-andsocket junctions with endothelial cells (mature core). A condensed plasmatic electron-dense material surrounded and connected folds and pillars with each other and with the vascular wall, which suggests a clot role in fold/pillar arrangement. In conclusion, we contribute to IA participation in capillary network formation in angiolipoma and the immunohistochemical and ultrastructural events by which microthrombosis facilitates IA. Therefore, in addition to the histogenesis of angiolipoma, we provide an easily obtainable substrate for future studies on clot component action in IA, of clinical and therapeutic interest
Open Access
TBX3 stimulates proliferation and stem cell self-renewal in bladder carcinoma
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Huang, Lifu; Shao, Wenfei; Wang, Xiaohong; Li, Feiping; Mao, Weijun
Background. With the change of people’s lifestyle in recent years, bladder carcinoma has been the second leading cause of death for men. Nevertheless, surgical results of bladder carcinoma are unsatisfying with recurrence and distant metastasis. Therefore, it is urgent to find a new target for bladder carcinoma treatment. Methods. The protein and mRNA expression levels of TBX3 in bladder carcinoma tissue samples and cells were tested using western blot and qRT-PCR assays, respectively. Cancer stem cells (CSCs) were separated with immunomagnetic beads. Expression levels of cell stemness-associated proteins CD44, CD24 and ESA in T24 CSCs and T24 cells were detected by western blot assay. Cell self-renewal ability was detected by stem cell sphere formation assay. CCK-8 and colony formation assays examined cell viability and proliferation. Cell apoptotic level was examined by flow cytometry. Results. Elevated TBX3 expression in bladder carcinoma stimulated cell proliferation and inhibited cell apoptosis. Stemness-related proteins and TBX3 were highly expressed in T24 CSCs relative to those in normal bladder carcinoma cells. In addition, TBX3 promoted stem cell self-renewal and inhibited cell apoptosis. Finally, qRT-PCR, western blot and cell sphere formation assays revealed that the potential role of TGF-β1 in the regulation of TBX3. Conclusion. TBX3, mediated by TGF-β1, can promote bladder carcinoma cell proliferation, inhibit apoptosis, and enhance cell stemness. Hence, TBX3 is a potential target to stem cells of bladder carcinoma.
Open Access
Circ_0000520 interacts with miR-512-5p to upregulate KIAA0100 to promote malignant behaviors in lung cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wang, Linxuan; Liu, Yuan; Wu, Xiaochi; Liu, Yuan; Gu, Wenchao
Background. CircRNAs function as pivotal molecules to regulate the malignant development of lung cancer. This study was designed to research the functional role and how it acted in lung cancer progression. Methods. Circ_0000520, microRNA-512-5p (miR512-5p) and Breast cancer-overexpressed gene 1 (KIAA0100) levels were measured through reverse transcription-quantitative polymerase chain reaction assay. Cell Counting Kit-8 assay and EdU assay were used to examine cell proliferation. Cell cycle and apoptosis were evaluated via flow cytometry. The protein levels were determined using western blot. Cell migration and invasion were assessed by wound healing assay and transwell assay. The circ_0000520 function in vivo was explored by tumor xenograft assay. The molecular interaction was analyzed via Dual-luciferase reporter assay. Results. Circ_0000520 was obviously upregulated in lung cancer tissues and cells. Silence of circ_0000520 inhibited proliferation, cell cycle progression, migration, invasion and angiogenesis but promoted cell apoptosis. Circ_0000520 downregulation reduced tumor growth of lung cancer in vivo. Circ_0000520 served as a miR-512- 5p sponge. The oncogenic function of circ_0000520 was partly achieved by sponging miR-512-5p in lung cancer. KIAA0100 was a target of miR-512-5p and miR-512-5p inhibited the malignant behaviors of lung cancer cells via downregulating KIAA0100. Circ_0000520 targeted miR-512-5p to regulate the level of KIAA0100. Conclusion. All these data demonstrated that circ_0000520 was able to drive the progression of lung cancer via the mediation of miR-512-5p/KIAA0100 axis. Circ_0000520 might be a potential biomarker for lung cancer.
Open Access
Role of stress-related glucocorticoid changes in astrocyte-oligodendrocyte interactions that regulate myelin production and maintenance
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Miguel Hidalgo, José Javier
Repeated activation of stress responses and elevated corticosteroids result in alterations of neuronal physiology and metabolism, and lead to disturbances of normal connectivity between neurons in various brain regions. In addition, stress responses are also associated with anomalies in the function of glial cells, particularly astrocytes and oligodendrocytes, which in turn may further contribute to the mechanisms of neuronal dysfunction. The actions of corticosteroids on astrocytes are very likely mediated by the presence of intracellular and cell membrane-bound CORT receptors. Although apparently less abundant than in astrocytes, activation of CORT receptors in oligodendrocytes also leads to structural changes that are reflected in myelin maintenance and plasticity. The close interactions between astrocytes and oligodendrocytes through extracellular matrix molecules, soluble factors and astrocyte-oligodendrocyte gap junctions very likely mediate part of the disturbances in myelin structure, leading to plastic myelin adaptations or pathological myelin disruptions that may significantly influence brain connectivity. Likewise, the intimate association of the tips of some astrocytes processes with a majority of nodes of Ranvier in the white matter suggest that stress and overexposure to corticosteroids may lead to remodeling of node of Ranvier and their specific extracellular milieu

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