Histology and histopathology Vol.38, nº3 (2023)
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- PublicationOpen AccessCirc_0031242 regulates the functional properties of hepatocellular carcinoma cells through the miR-944/MAD2L1 axis(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Lin, Jianwei; Lin, Zenghai; Hua, Yaqiong; Chen, YanBackground. Circular RNAs (circRNAs) possess key functions in the pathogenesis of hepatocellular carcinoma (HCC). Nonetheless, the actions of individual circRNAs in HCC remain undefined. Methods. circ_0031242, miR-944, and MAD2L1 expression were quantified by qRT-PCR. Transwell assay was utilized to examine cell invasion and migration. Glucose consumption and lactate production were measured to assess the impact on glycolysis. The relationships among circ_0031242, MAD2L1, and miR944 were examined via luciferase reporter assay. Results. circ_0031242 was notably augmented in HCC. Loss of function of circ_0031242 hindered cell proliferation, invasion, migration, glycolysis, and promoted apoptosis, as well as impeding HCC tumor growth. circ_0031242 directly targeted miR-944. Inhibition of miR-944 counteracted the effects of sicirc_0031242 on HCC cells. Additionally, miR-944 was proved to directly target MAD2L1 in HCC cells. Moreover, the promotion of MAD2L1 was able to rescue the inhibition of high miR-944 expression on HCC cell progression. Meanwhile, circ_0031242 involved the post-transcriptional modulation of MAD2L1 through miR-944. Conclusion. This study suggested that circ_0031242 regulated tumor cell progression and tumor growth through the miR-944/MAD2L1 axis in HCC.
- PublicationOpen AccessCircular RNA circ_SKA3 enhances gastric cancer development by targeting miR-520h(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wang, Chuntao; Jiang, Hao; Peng, Jiaqun; Weng, Duanshun; Zhang, Yu; Zhou, Yanxun; Zhang, QinPurpose. To explore the mechanisms of action of circ_SKA3 in gastric cancer (GC), which are still not fully understood. Methods. Subcellular localization assay was used to analyze the localization of circ_SKA3, and Actinomycin D assay was applied to confirm the stability of circ_SKA3. The levels of circ_SKA3, microRNA (miR)- 520h, and cell division cycle 42 (CDC42) mRNA were gauged by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of CDC42 and proliferating cell nuclear antigen (PCNA) were assessed by western blot. Cell proliferation, colony formation, cell cycle distribution, apoptosis, migration, and invasion were detected by 3-[4,5-dimethylthiazol-2-yl]- 2, 5-diphenyltetrazolium bromide (MTT), 5-Ethynyl-2’- Deoxyuridine (EdU) incorporation, colony formation, flow cytometry, and transwell assays, respectively. Directed relationship between miR-520h and circ_SKA3 or CDC42 was verified by a dual-luciferase reporter assay. Mouse xenograft experiments were used to elucidate the impact of circ_SKA3 in vivo. Results. Overexpression of circ_SKA3 was validated in GC tissues and cells. The down-regulation of circ_SKA3 suppressed proliferation, cell cycle progression, colony formation, migration, invasion, and promoted cell apoptosis in vitro, as well as weakening tumor growth in vivo. Circ_SKA3 directly bound to miR-520h, and circ_SKA3 regulated CDC42 expression through miR-520h. Circ_SKA3 exerted regulatory effects on GC cell behaviors by inhibiting miR-520h. Furthermore, CDC42 was a functional target of miR520h in regulating GC cell behaviors. Conclusion. Our findings established a strong molecular mechanism, the miR-520h/CDC42 axis, at least in part, for the oncogenic role of circ_SKA3 in GC.
- PublicationOpen AccessExpression of Foxp3 and TLR4 in human papillary thyroid carcinoma and its clinical significance(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Xin, Jingwei; Fu, Haiying; Zhang, Jiaping; Zou, Hongrui; Li, Qi; Yang, Wei; Sun, HuiThis study aimed to explore the association of Foxp3 and TLR4 with clinical pathological characteristics in papillary thyroid carcinoma (PTC) patients. Methods 78 cases of PTC were used as experimental group and 20 cases of normal thyroid tissue were used as control group. The expression of Foxp3 and TLR4 in thyroid tissue from the two groups was detected by immunohistochemistry, and the experimental group was divided into several groups on the basis of different clinicopathological indicators. The association between Foxp3 and TLR4 expression and clinicopathological parameters was statistically analyzed. Results Foxp3 and TLR4 were expressed in higher levels in PTC than in normal thyroid tissue (P<0.05). Foxp3 was mainly localized in the cytoplasm and nucleus of PTC cells, while TLR4 was found in the cytoplasm and cell membrane of cancer cells. The expression of both proteins associated with lymph node metastasis and TNM clinical stage (P<0.05). The expression of Foxp3 correlated with the expression of TLR4 in tested PTC tissues (P<0.05). In addition, the result of confocal fluorescence microscopy showed that Foxp3 and TLR4 co-localized in PTC cells. Conclusion Foxp3 and TLR4 were upregulated and associated with lymph node metastasis and advanced TNM stage in PTC tissues. Together they may act as valuable factors for the identification of high-risk PTC patients.
- PublicationOpen AccessThe circCDK17/miR-122-5p/ASF1B axis regulates the progression of cervical cancer(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Qiu, Fang; Ou, Dafen; Tan, Hanxing; Gao, Yan; Z, DanBackground. Cervical cancer (CC) ranks fourth in terms of incidence and fourth in mortality overall in women worldwide. Circular RNAs (circRNAs) have been shown to be involved in the development of CC. However, the function of circRNA cyclin dependent kinase 17 (circCDK17, hsa_circ_ 0002762) in CC pathogenesis has not been studied. Methods. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of related genes. MTT, thymidine analog 5-ethynyl-2’- deoxyuridine (EdU), flow cytometry, transwell and wound-healing assays were designed to analyze cell proliferation, cell cycle progression, migration and invasion, respectively. Western blot was utilized to examine the protein levels of Cyclin D1, E-cadherin and Vimentin. The relationship between miR-122-5p and circCDK17 or ASF1B was verified by dual-luciferase reporter assay. The xenograft model was established to study the role of circCDK17 in vivo. Results. CircCDK17 and anti-silencing function 1B histone chaperone (ASF1B) were highly expressed in CC tissues and cells. Silencing circCDK17 reduced the proliferation, migration and invasion of CC cells. MiR122-5p was a target of circCDK17. Silencing circCDK17 inhibited the malignant behaviors of CC cells by releasing miR-122-5p. Moreover, ASF1B was a target of miR-122-5p. Overexpression of ASF1B partially restored the inhibitory effects of circCDK17 silencing on cell proliferation, migration and invasion. Animal experiments confirmed the anti-tumor effect of circCDK17 knockdown in vivo. Conclusion. Our study demonstrates that circCDK17 regulates the expression of ASF1B by miR-122-5p competition and thus promotes the development of CC, providing a novel targeted therapy for CC.
- PublicationOpen AccessUp-regulation of CMKLR1 in endometriosis and its relationship with inflammatory responses(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Zhang, Zhe; Ding, Yumei; Li, Junjie; Su, ShanInflammation plays a critical role in the pathogenesis of endometriosis. We aimed to study the proinflammatory effect of Chemerin chemokine-like receptor 1 (CMKLR1) in patients with endometriosis. Sixty patients with endometriosis and 50 healthy controls were recruited in this study for the collection of endometrial samples and peritoneal fluid. The expression levels of CMKLR1, IL-6, MCP-1, and TNFα in peritoneal fluid and endometrial tissues were detected by ELISA, qRT-PCR, and immunohistochemical staining. Human endometrial stromal cells (HESCs) were used to measure the Chemerin-induced CMKLR1 activation and inflammatory responses. CMKLR1 level was significantly up-regulated in peritoneal fluid and endometrial tissues in patients with endometriosis. Interestingly, CMKLR1 overexpression positively correlated with pro-inflammatory cytokines and chemokine in both peritoneal fluid and ectopic endometrium. Chemerin treatment increased the expression of CMKLR1, and aggravated inflammatory responses in HESCs. CMKLR1 is up-regulated in peritoneal fluid and endometrial tissues, and promotes the inflammatory responses in of endometriosis.