Histology and histopathology Vol.40, nº1 (2025)

Ir a Estadísticas

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http://hdl.handle.net/10201/179974

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Open Access
Hsa_circ_0070440 mediates the prognosis and progress of human prostate cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Huang, Min; Zhang, Junming; Luo, Wentao; Li, Tingting; Song, Qiong; Zhang, Lixiao; Cao, Min; Li, Shuang
Background. This study was designed to explore whether hsa_circ_0070440 was dysregulated in prostate cancer (PCa), and assess the effects of hsa_circ_0070440 alteration on PCa prognosis and cell function. Methods. The expression levels of hsa_circ_ 0070440 were assessed in PCa tissues and cell lines. After the classification of patients with PCa based on mean hsa_circ_0070440 level in 138 cases, Chi-square test and survival analyses (Kaplan-Meier method and multivariable Cox proportional hazards analysis) were performed to assess the predictive value of hsa_circ_0070440 in treatment failure (TTF), time to PSA progression (TTPP) and overall survival time. To examine the function of hsa_circ_0070440 in PCa cells, 22Rv1 and C4-2B cells were used for CCK-8 proliferation and Transwell migration assays. Hsa_circ_0070440- and TXNDC5-specific bindings with miR-382/383-5p were validated by bioinformatic analysis and luciferase gene reporter assay. Results. An increased expression of hsa_circ_ 0070440 was found in PCA tissues and cell lines, associated with clinical T stage (p=0.021) and lymph node metastasis. Hsa_circ_0070440 predicted poor overall survival, TTPP, and TTF, acting as independent prognostic factors for overall survival, TTPP, and TTF in patients with PCa. Knockdown of hsa_circ_0070440 inhibited cell proliferation and migration in vitro. Furthermore, hsa_circ_0070440 could sponge miR-382/383-5p. TXNDC5 was a common target gene for miR-382/383-5p in PCa cells. Conclusion. This study demonstrated that hsa_circ_0070440 can predict the prognosis of PCa patients. Hsa_circ_0070440 can facilitate the proliferation and migration of PCa cells, possibly by sponging miR-382/383-5p
Open Access
Cyclin-dependent kinase 5 as a potential therapeutic target to alleviate high glucose-induced podocyte apoptosis and hyperglycemia-induced renal injury in mice
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Zhao, Li; Gu, Wenjuan; He, Wenfang; Yang, Kaibi; Yang, Nan; Jia, Yanqing
Background. Hyperglycemia is a risk factor for impaired renal function, including cellular metabolic disturbance, apoptosis, inflammation, and histologic lesion. This study aims to investigate the potential therapeutic targeting of cyclin-dependent kinase 5 (Cdk5) in hyperglycemia-induced podocyte dysfunction and renal damage. Methods. Cell viability and apoptosis of podocytes were assessed through CCK-8 and TUNEL staining, respectively, following exposure to normal glucose (NG; 5 mM), high glucose (HG; 30 mM), or treatment with Cdk5 inhibitors (trans-resveratrol, myricetin, salvianolic acid A, and BML-259). Diabetic mice were established by intraperitoneal injection of freshly streptozotocin (STZ), which was given at a dose of 35 mg/kg in five successive injections. Additionally, histochemical staining was employed to evaluate the morphologic lesion of the kidney. Results. Cdk5 was found to be activated by HG stimulation both in vitro and in vivo. Notably, the inhibition of Cdk5 effectively mitigated the podocyte dysfunction induced by HG, including growth inhibition, membrane damage, and apoptosis. The compounds Trans-resveratrol, myricetin, salvianolic acid A, and BML-259 exhibited low binding energy values of -8.032 kcal/mol, -8.693 kcal/mol, -8.743 kcal/mol, and -10.952 kcal/mol, respectively, indicating strong and stable binding affinity between these candidates and Cdk5. The results of in vivo experimental analysis demonstrate that Cdk5 inhibitors, namely trans-resveratrol, myricetin, salvianolic acid A, and BML-259, confer protection against tubular and glomerular lesions induced by hyperglycemia. Conclusion. Both myricetin and BML-259 exhibit comparable protective effects on renal injury by inhibiting Cdk5
Open Access
NRF3 suppresses the metastasis of triple-negative breast cancer cells by inhibiting ERK activation in a ROS-dependent manner
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Zheng, Chenhui; Pan, Yue; Lin, Bangyi; Li, Jin; Chen, Qi; Zheng, Zhibao
Purpose. Our previous study demonstrated that NRF3 (NFE2L3, Nuclear Factor-erythroid 2-related factor 3) could suppress cell metastasis and proliferation in breast cancer. In this study, we investigated the mechanisms underlying its function in breast cancer. Methods. In the present study, NRF3 expression and its clinical characteristics in breast cancer were analyzed using public datasets and clinical specimens. After breast cancer cells were overexpressed NRF3, FACS was used to detect the intracellular ROS levels. The migration and invasion activities of NRF3-ectopic expressed breast cancer cells were determined by transwell assay. To validate the role of ROS/ERK axis in the inhibitory effect of NRF3 in cell metastasis, ROS scavenger NAC was also included. Results. We found that NRF3 mRNA was highly expressed, while NRF3 protein was extremely lowly expressed in breast cancer tissues compared with their normal counterparts, and low level NRF3 was associated with poorer prognosis in patients with triple negative breast cancer (TNBC). More interestingly, over-expression of NRF3 protein significantly increased cellular ROS production and dramatically decreased p-ERK level and cell migration in TNBC cells. Mechanistically, NRF3 protein was found to be mutually regulated by valosin-containing protein (VCP). Strikingly, VCP-knockdown dramatically increased NRF3 protein expression, but NRF3-knockin also decreased VCP expression in return. Moreover, antioxidant NAC treatment effectively increased the level of p-ERK and VCP expression, as well as cell migration and invasion abilities of TNBC cells. Conclusion. NRF3, a tumor suppressor down-regulated by VCP, could attenuate cell metastasis in TNBC cells by increasing cellular ROS accumulation and subsequently inhibiting the ERK phosphorylation.
Open Access
PYCR1 expresses in cancer-associated fibroblasts and accelerates the progression of C6 glioblastoma
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Zhang, Mingkun; Bi, Baibin; Liu, Guangcun; Fan, Xiaoyong
Background. Cancer-associated fibroblasts (CAFs) play important roles in tumor micro-environments. Pyrroline-5-carboxylate reductase 1 (PYCR1) is a potential cancer therapy target. This study aimed to explore the expression of PYCR1 in glioma-associated CAFs and analyze the effects of PYCR1 expression in CAFs on the proliferation of C6 glioma. Methods. A rat glioma model was induced by injecting C6 cells in the right caudate putamen via a microliter syringe. After 14 days, tumor tissues were collected, and the levels of COL1A1 and PYCR1 were measured by immunohistochemistry. The colocalization of fibroblast activation protein α (FAP) and PYCR1 in tissues was measured by double-immunofluorescence. The CAFs were labeled by FAP and isolated from the tumor tissues using a fluorescence-activated cell sorting (FACS) machine. The isolated CAFs were further separated into CAFs with different PYCR1 expressions using the FACS machine. CAFs with different PYCR1 expressions were respectively cocultured with C6 cells or MUVECs for 48h using a Transwell permeable support. The invasion and proliferation of C6 cells were measured using a Transwell assay and colony formation assay, and the angiogenesis of MUVECs was measured using a Tube formation assay. The expression of COL1A1 and PYCR1 proteins in C6 cells and VEGF-A and EGF proteins in MUVECs was measured by western blotting. PYCR1 silencing in C6 cells was induced by PYCR1 siRNA transfection, the effects of which on the proliferation of C6 cells were measured using a wound healing assay, a Transwell assay, and western blotting. Results. The PYCR1 and COL1A1 upregulation co-occurred in the rat glioma, and PYCR1 was expressed in CAFs. The CAF coculture enhanced the invasion and proliferation of C6 cells and the angiogenesis of MUVECs. Meanwhile, the levels of COL1A1 protein in C6 cells, and the levels of VEGF-A and EGF proteins in MUVECs were increased after CAF coculture. Moreover, the effects of CAF coculture were increased with PYCR1 expression in the CAF. Silencing PYCR1 suppressed the migration and invasion of C6 cells, and decreased the levels of COL1A1 and VEGF-A proteins in C6 cells. Conclusions. PYCR1 is expressed in glioma-associated CAFs, and promotes the proliferation of C6 cells and angiogenesis of MUVECs, suggesting that targeting PYCR1 may be a therapeutic strategy for glioma.
Open Access
Association of low angiomotin-p130 and high YAP1 nuclear expression with adverse prognosis in epithelial ovarian cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Cai, Junna; Han, Xiaorui; Li, Meng; Liu, Xiaoli; Zhang, Fengying; Wu, Xiaohua
Objectives. The aim of our study was to examine the association of Angiomotin (Amot-p130) and Yes-associated protein 1 (YAP1) expressions and their prognostic significance in epithelial ovarian cancer (EOC). Methods. A total of 100 primary EOC samples were obtained for immunohistochemical analysis of Amot-p130 and YAP1 expressions. Correlation analysis was performed between Amot-p130 or YAP1 and clinical factors. The overall survival time was calculated. Results. Low Amot-p130 and high YAP1 nuclear expression were identified in 34 and 56 of 100 EOC tissues, respectively. Both low Amot-p130 and high YAP1 nuclear expression were associated with advanced tumor stage, high-grade carcinoma, and non-response to chemotherapy (p<0.05). They were also associated with shorter overall survival time (p<0.05) by log-rank test. A marker of low Amot-p130 and high YAP1 expression was associated with high-grade ovarian carcinoma, late-stage disease, non-response to chemotherapy, and shorter overall survival time (p<0.05). Conclusions. Low Amot-p130 and high YAP1 nuclear expression can provide additional prognostic information for patients with EOC. A marker of low Amot-p130 and high YAP1 expression may be a potent predictor of poor prognosis in patients with epithelial ovarian cancer.

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