Histology and histopathology Vol.38,nº10 (2023)
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- PublicationOpen AccessExtra-meningeal solitary fibrous tumor: an evolving entity with chameleonic morphological diversity, a hallmark molecular alteration and unresolved issues in risk stratification assessment(Universidad de Murcia. Departamento de Biología Celular e Histología, 2023) Machado, Isidro; Giner, Francisco; Cruz, Julia; Lavernia, Javier; Marhuenda Fluixa, Ana; Claramunt, Reyes; López Guerrero, José Antonio; Navarro, Samuel; Ferrandez, Antonio; Blázquez Bujeda, Álvaro; Ruiz-Sauri, Amparo; Llombart Bosch, AntonioSolitary fibrous tumor (SFT) is a rare type of mesenchymal lesion with variable clinical presentation in which specific clinicopathologic factors have been related to patient outcome. SFT shares an important morphologic and immunohistochemical overlap with other sarcomas, hence the differential diagnosis is challenging. Although molecular studies provide significant clues, especially in the differential diagnosis with other neoplasms, a thorough hematoxylin and eosin analysis and the integration of phenotypical, clinical, and radiological features remain an essential tool in SFT diagnosis. In this review, we discuss some emerging issues still under debate in SFT.
- PublicationOpen AccessMiR-101-3p targets KPNA2 to inhibit the progression of lung squamous cell carcinoma cell lines(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Dong, Liangliang; Jiang, Hanliang; Qiu, Ting; Xu, Yiming; Chen, Enguo; Huang, Aihua; Ying, KejingWe herein discuss the impacts of miR-101-3p on the tumorigenesis-related cell behaviors in lung squamous cell carcinoma (LUSC) by repressing KPNA2. TCGA database was utilized to measure miR101-3p and KPNA2 levels in LUSC tissues and cells. The interaction of miR-101-3p and KPNA2-3’UTR was determined by dual luciferase assay. Western blot evaluated the protein level of KPNA2. MiR-101-3p was under-expressed in LUSC cells while KPNA2 was overexpressed. Western blot confirmed the impact of KPNA2 expression on cancer cell progression. The negative regulatory impact of miR-101-3p on KPNA2 was also verified. In vitro cell function assays revealed the suppressing effect of high miR-101-3p expression on cell invasion, migration and viability, as well as its promoting effect on apoptosis. Up-regulated miR-101-3p weakened the promoting effect of overexpressed KPNA2 on LUSC malignant progression. To conclude, miR-101-3p repressed viability, invasion, and migration, and facilitated cell apoptosis in LUSC by suppressing KPNA2.
- PublicationOpen AccessImmunohistochemical evaluation of tissues following bone implant extraction from upper and lower limb(Universidad de Murcia. Departamento de Biología Celular e Histología, 2023) Bielniková Kryštofová, Hana; Motyka, Oldřich; Židlík, Vladimír; Žiak, Dušan; Szotkovská, Iveta; Škarda, Jozef; Pometlová, Jana; Pleva, Leopold; Havlíček, Miroslav; Čabanová, KristinaFractured bones can regenerate and restore their biological and mechanical properties to the state prior to the damage. In some cases, however, the treatment of fractures requires the use of supportive implants. For bone healing, three processes are essential: the inflammatory phase, the repair phase and the remodelling phase. A proper course of the first - inflammatory - stage is important to ensure a successful fracture healing process. In our study, we evaluated tissue samples immunohistochemically from the area surrounding the fractures of upper and lower limbs (bone tissue, soft tissue, and the implant-adhering tissue) for markers: CD11b, CD15, CD34, CD44, CD68, Cathepsin K, and TRAcP that are linked to the aforementioned phases. In soft tissue, higher expressions of CD68, CD34, CD15 and CD11b markers were observed than in other locations. TRAcP and Cathepsin K markers were more expressed in the bone tissue, while pigmentation, necrosis and calcification were more observed in the implant-adhering tissue. Since even the implant materials commonly perceived as inert elicit the observed inflammatory responses, new surface treatments and materials need to be developed.
- PublicationOpen AccessHistopathological characteristics of adenomyosis: structure and microstructure(Universidad de Murcia. Departamento de Biología Celular e Histología, 2023) Liu, Ziyu; Guo, Yanxian; Pan, Xinyi; Yang, XingAdenomyosis is a benign uterine disease that pathologically shows endometrial glands and stroma in the myometrium. There are multiple lines of evidence that adenomyosis is associated with abnormal bleeding, painful menstruation, chronic pelvic pain, infertility, and spontaneous pregnancy loss. Pathologists have researched adenomyosis by studying tissue specimens from its first report more than 150 years ago, and differing viewpoints on its pathological alterations have been advanced. However, the gold standard histopathological definition of adenomyosis remains controversial to date. The diagnostic accuracy of adenomyosis has steadily increased due to the continual identification of unique molecular markers. This article provides a brief description of the pathological aspects of adenomyosis and discusses adenomyosis categorization based on histology. The clinical findings of uncommon adenomyosis are also presented to offer a thorough and detailed pathological profile. Furthermore, we describe the histolog
- PublicationOpen AccessCirc_0000284 facilitates the growth, metastasis and glycolysis of intrahepatic cholangiocarcinoma through miR-152-3p-mediated PDK1 expression(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Sun, Jian; Feng, Menglong; Zou, Huilian; Mao, Yanping; Yu, WeiBackground. Circular RNAs (circRNAs) are key molecules in the regulation of intrahepatic cholangiocarcinoma (ICC) progression. The purpose of this study was to analyze the function and underlying molecular mechanism of circ_0000284 in ICC. Methods. Quantitative real-time PCR was used to analyze the circ_0000284, microRNA (miR)-152-3p and pyruvate dehydrogenase kinase 1 (PDK1) expression. Cell proliferation, apoptosis, invasion and migration were executed by cell counting kit 8 assay, EdU assay, flow cytometry, transwell assay and wound healing assay, respectively. All protein expression levels were examined using western blot analysis. Cell glycolysis was analyzed by detecting glucose consumption, lactate production and ATP/ADP ratios. Target relationship was estimated by dual-luciferase reporter assay. The effect of circ_0000284 on ICC tumor growth in vivo was evaluated by constructing xenograft mice model. Results. We detected high expression of circ_0000284 in ICC tumor tissues and cells. Downregulated circ_0000284 inhibited ICC cell proliferation, invasion, migration, glycolysis, and accelerated apoptosis. MiR-152-3p was sponged by circ_0000284, and its inhibitor revoked the effect of circ_0000284 knockdown on ICC cell progression. PDK1 was a target of miR-152-3p, and its expression was suppressed by circ_0000284 knockdown. PDK1 overexpression reversed the inhibition effect of miR-152-3p on ICC cell growth, metastasis and glycolysis. In animal experiments, circ_0000284 downregulation also inhibited ICC tumor growth. Conclusion. Circ_0000284 promoted the growth, metastasis and glycolysis of ICC by miR-152-3p/PDK1 pathway, showing that circ_0000284 was a potential therapeutic target for ICC.
- PublicationOpen AccessDoxorubicin resistance in breast cancer xenografts and cell lines can be counterweighted by microRNA-140-3p, through PD-L1 suppression(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Zhang, Xia; Wang, Chao; Huang, Cuiping; Yang, Jianbao; Wang, JuanBackground. Doxorubicin, a first-line chemotherapeutic drug for breast cancer, kills cancer cells by inducing DNA-crosslinking damage. Dysregulated micro-RNA (miRNA) is associated with the drug resistance of tumors. However, little is known about the effect of miRNA-140-3p on DOX resistance of breast cancer. Methods. The miRNA microarray was used to sequence the transcripts of DOX-chemoresistant breast cancer tissues and DOX-chemosensitive tissues. Then, the breast cancer tissue chip in the GEO database was also analyzed to screen the target gene. Flow cytometry, in situ hybridisation (ISH), immunohistochemistry (IHC), Western blot, cell proliferation assay, real-time PCR analyses (qRT-PCR), and pull-down assay were used to explore the effects of miRNA-140-3p and programmed death ligand-1 (PD-L1) on the chemoresistance of DOX-resistant breast cancer cells treated with DOX. In vivo, the DOX-resistant breast cancer cell lines treated with miRNA-140-3p overexpression were injected subcutaneously into mice to construct breast cancer subcutaneous xenograft tumor models. Results. Based on miRNA microarray, GEO database, and bioinformatics analysis, it was found that miRNA-140-3p and PD-L1 are the core molecules in the DOX resistance regulatory network in breast cancer, and lower miRNA-140-3p and higher PD-L1 expression levels were observed in DOX-resistant breast cancer tissues and cells. IHC results showed that compared with breast cancer tissues with high miRNA-140-3p expression, PD-L1 protein expression levels in breast cancer tissues with low miRNA-140-3p were significantly higher (P<0.01). Moreover, compared with DOX-sensitive tissues, the levels of PD-L1 protein expression in DOX-resistant tissues were significantly higher (P<0.01). In in vitro and in vivo experiments, the introduction of miRNA-140-3p decreased PD-L1 expression. Mechanically, we found that the MCF7/DOX and HS598T/DOX cells pretreated with miRNA140-3p inhibitor or exosomes containing PD-L1 have higher stemness and lower apoptosis rate, which can be abrogated by co-treating cells with anti-PD-L1 antibody or miRNA-140-3p mimic. Conclusions. MiRNA-140-3p can suppress PD-L1 expression in breast cancer cell-derived exosomes, thereby attenuating the chemoresistance induced by DOX in breast cancer.
- PublicationOpen AccessCirc-0000979 promotes the development of gastric carcinoma by sponging miR-136 and modulating SP1 mRNA expression level(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Zhang, Lihua; Xing, Fengjuan; Bao, LeiCircular RNAs (circRNAs) are a new class of non-coding RNAs that play pivotal biological roles in several types of cancer cells. However, the role of circ0000979 in gastric cancer (GC) has never been explored. Therefore, the current study aims to examine the functional effects of circ-0000979 in GC development and progression. The expression level of circ-0000979 was validated using qRT-PCR analysis. We found that circ-0000979 is significantly upregulated in GC samples. Using AGS and HGC27 GC cell line, we examined the biological functions and regulatory mechanisms of circ0000979 in GC in vitro and in vivo by knocking down circ-0000979. We found that circ-0000979 is subcellularly localized in the cytoplasm of GC cells. Functionally, silencing circ-0000979 leads to a significant reduction in GC cell proliferation and migration. In vivo assays showed that circ-0000979 knockdown markedly reduced GC tumor growth. CircRNA interactome predicted miR-136 as circ0000979 targeting miRNA, while starbase prediction result showed that miR-136 targeted the 3’UTR region of SP1 mRNA. Taken together, our results demonstrated that circ-0000979, as a carcinogenic circRNA, promotes the progression of GC by regulating the miR-136/SP1 pathway. Circ-0000979 is a potential RNA-based therapeutic target for GC treatment.
- PublicationOpen AccessCirc-CCS regulates oxaliplatin resistance via targeting miR-874-3p/HK2 axis in colorectal cancer(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Qiu, Xiaofeng; Xu, Qihua; Liao, Bingling; Hu, Sheng; Zhou, Ying; Zhang, HuijunBackground. Colorectal cancer (CRC) is a malignancy that threatens the patient’s life. Previous reports showed that circular RNAs (circRNAs) can affect CRC development. Herein, we demonstrated the characters of circular RNA copper chaperone for superoxide dismutase (circ-CCS) in CRC tissues and cells. Methods. Circ-CCS, CCS mRNA, microRNA-8743p (miR-874-3p) and hexokinase 2 (HK2) were indicated by qRT-PCR and western blot in CRC. The cell roles were examined. Additionally, the interaction between miR-874-3p and circ-CCS or HK2 was forecasted by the bioinformatics method and assessed by dual-luciferase reporter assay. Finally, the mouse test was implemented to demonstrate the effect of circ-CCS in vivo. Results. Circ-CCS and HK2 were increased, whereas miR-874-3p was diminished in CRC. Circ-CCS lack subdued the IC50 value of oxaliplatin, cell proliferation, migration, invasion and glycolysis metabolism in CRC cells, while it endorsed cell apoptosis. Furthermore, miR-874-3p was validated as having a tumor repressive effect in CRC cells by restraining HK2. The results also showed that HK2 could regulate the development of CRC. In mechanism, circ-CCS targeted miR-874-3p to control HK2. In addition, circ-CCS knock-down also attenuated tumor growth in mice. Conclusion. Circ-CCS expedited CRC through miR874-3p/HK2
- PublicationOpen AccessMatrine inhibits hepatocellular carcinoma cell malignancy through the circ_0013290/miR-139-5p/MMP16 pathway(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Chang, Xinfeng; Huang, Zhengchun; Zhang, Zhihua; Pan, Wen; Song, ChunhuaBackground. Previous studies have shown the anticancer effect of Matrine on hepatocellular carcinoma (HCC); however, the underlying mechanism is still indistinct. Methods. The expression of circular RNA_0013290 (circ_0013290), microRNA-139-5p (miR-139-5p), matrix metallopeptidase 16 (MMP16), CyclinD1 and N-cadherin was analyzed by quantitative real-time polymerase chain reaction, Western blotting or immuno-histochemistry assay. Cell viability, proliferation, apoptosis, invasion and tube formation were analyzed by cell counting kit-8, 5-Ethynyl-2’-deoxyuridine, flow cytometry analysis, transwell invasion and tube formation assays, respectively. The associations among circ_0013290, miR-139-5p and MMP16 were predicted by starbase online database, and identified by dual-luciferase reporter and RNA pull-down assays. A xenograft mouse model assay was conducted to disclose the effects of circ_0013290 and Matrine on tumor tumorigenesis in vivo. Results. Circ_0013290 and MMP16 expression were significantly upregulated, while miR-139-5p was downregulated in HCC tissues and cells compared with the matched normal liver tissues and cells. Matrine treatment inhibited HCC cell proliferation, invasion and tube formation but induced cell apoptosis, accompanied by the decrease of CyclinD1 and N-cadherin expression; however, these effects were counteracted when circ_0013290 expression was increased. MiR-139-5p depletion or MMP16 introduction relieved Matrine-induced effects in HCC cells. The regulation of circ_0013290 toward HCC cell processes involved MMP16. With respect to the mechanism, circ_0013290 acted as a miR-139-5p sponge, and miR-139-5p targeted MMP16 in HCC cells. Besides, circ_0013290 regulated MMP16 expression through miR-139-5p. Further, circ_0013290 depletion enhanced the inhibitory effects of Matrine on tumor tumorigenesis. Conclusion. Matrine inhibited HCC cell malignancy through the circ_0013290/miR-139-5p/MMP16 pathway, suggesting that Matrine is a potential therapeutic agent for HCC
- PublicationOpen AccessHyperin up-regulates miR-7031-5P to promote osteogenic differentiation of MC3T3-E1 cells(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Qian, Dongchen; Chen, Yueyue; Qiu, Xusheng; Zhu, Baohua; Zhang, Lin; Yan, Yifeng; Chen, YixinObjective. To investigate the effects of Hyperin (Hyp) on osteogenic differentiation of MC3T3E1 cells. Methods. Differentially expressed miRNA was screened by miRNA Microarray. miR-7031-5P overexpression and knockdown MC3T3-E1 cell models were constructed by transfecting miR-7031-5P mimics and inhibitor. Alizarin red staining (ARS) assay was used to observe the formation of mineralized nodules in MC3T3-E1 cells. ALP activity was detected by using ALP detection kit. Western blot assay was used to examine the changes in osteogenic differentiation-related proteins. The relationship between miR-7031-5P and Wnt7a was revealed by dual luciferase report experiments. Results. We found that miR-7031-5P was upregulated in MC3T3-E1 cells after Hyp treatment. The results indicated that compared with the untreated group, Hyp promoted the formation of mineralized nodules and the alkaline phosphatase (ALP) activity of MC3T3-E1 cells via overexpressing miR-7031-5P. Besides, elevated miR-7031-5P increased OPN, COL1A1, and Runx2 mRNA expression. More importantly, Wnt7a was identified as the downstream target gene of miR-70315P promoting osteogenic differentiation of MC3T3-E1 cells. Conclusions. Hyp up-regulated miR-7031-5P to promote osteogenic differentiation of MC3T3-E1 cells by targeting Wnt7a
- PublicationOpen AccessWomen with psychotic episodes during pregnancy show increased markers of placental damage with Tenney-Parker changes(Universidad de Murcia. Departamento de Biología Celular e Histología, 2023) Ortega, Miguel A.; Fraile Martínez, Oscar; García Montero, Cielo; Rodriguez Martín, Sonia; Funes Moñux, Rosa M.; Pekarek, Leonel; Bravo, Coral; Leon Luis, Juan A. De; Saez, Miguel A.; Guijarro, Luis G.; Lahera, Guillermo; Monserrat, Jorge; Rodriguez Jimenez, Roberto; Saz, Jose V.; Buján, Julia; García Honduvilla, Natalio; Álvarez Mon, Melchor; Alvarez Mon, Miguel Angely. Psychosis is a hazardous and functionally disruptive psychiatric condition which may affect women in pregnancy, entailing negative consequences for maternofetal well-being. The precise pathophysiological basis and consequences of a psychotic episode in pregnancy remain to be further elucidated. The placenta is a pivotal tissue with many functions in the gestational period, critically influencing the fate and development of pregnancy. Although detrimental alterations have been observed in women undergoing severe psychiatric disorders in pregnancy, there are little studies evaluating the consequences of suffering from a psychotic episode in the placental tissue In this work, we have evaluated the histopathological consequences of a first episode of psychosis in pregnancy (FE-PW; N=22) and compare them with healthy pregnant women (HC-PW; N=20) by using histological, immunohistochemical and gene expression techniques. Our results define that the placental tissue of FE-PW display an increase in the number of placental villi, bridges, syncytial knots and syncytial knots/villi. Besides, we have also observed an enhanced gene and protein expression in FE-PW of the hypoxic marker HIF-1α, together with the apoptotic markers BAX and Bcl-2. To our knowledge, this is the first study demonstrating significant histopathological changes in the placenta of women suffering a new-onset psychotic episode in pregnancy. Further studies should be aimed at deepening the knowledge about the pernicious effects of psychosis in the maternofetal tissues, as well as the potential implications of these alterations.
- PublicationOpen AccessMiR-196a-5p facilitates progression of estrogen-dependent endometrial cancer by regulating FOXO1(Universidad de Murcia, Servicio de Publicaciones, 2023) Zhu, Yuzhang; Tang, Yanfei; Fan, Yaohua; Wu, DongjuanBackground and Purpose. Estrogen-dependent endometrial cancer mainly occurs in younger pre-menopausal and post-menopausal women and threatens their health. Recently, microRNAs (miRNAs) have been considered as novel targets in endometrial cancer treatment. Therefore, we aimed to explore the effect of miRNA (miR)-196a-5p in estrogen-dependent endometrial cancer. Methods. 17β-estradiol (E2; 2.5, 5, 10 and 20 nM) was used to treat RL95-2, HEC-1B and ECC-1 cells followed by cell viability assessment using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The level of miR-196a-5p was measured by reverse transcription-quantitative PCR (RT-qPCR). We then transfected miR-196a-5p mimic/inhibitor and Forkhead box protein O1 (FOXO1) small interfering RNA (siRNA) into E2-treated cells. Apoptotic cells were measured by flow cytometry. Wound healing and Transwell assays were implemented to assess migration and invasion. Bioinformatics and luciferase reporter assays were applied to confirm the interaction between miR-196a-5p and FOXO1. Immunoblotting determined the levels of FOXO1, Bcl-2, Bax, Caspase 3. Results. E2 promoted cell viability and miR-196a-5p expression in RL95-2 and ECC-1 cells. miR-196a-5p mimic enhanced cell viability, migration and invasion but suppressed apoptosis and FOXO1, whilst miR-196a-5p inhibitor blocked these processes. In addition, miR-196a-5p upregulated Bcl-2, but down regulated Bax and Caspase 3 expression, an effect that was reversed by miR-196a-5p inhibitor. We determined that miR-196a-5p targeted FOXO1, and that si-FOXO1 blocked the effects of miR-196a-5p inhibitor on viability, apoptosis, migration and invasion of E2-treated RL95-2 and ECC-1 cells. Conclusions. Our findings suggested potential diagnostic and therapeutic applications for miR-196a-5p and its FOXO1 target in patients suffering from estrogen-dependent endometrial cancer.