Browsing by Subject "Cervical cancer"
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- PublicationOpen AccessCirc_0085616 contributes to the radio-resistance and progression of cervical cancer by targeting miR-541-3p/ARL2 signaling(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Tang, Yan; Zhou, Lei; Liu, LiliBackground. Circular RNAs (circRNAs) play crucial regulatory roles in cancer progression and the development of radio-resistance. Here, we intended to explore the role of circ_0085616 in cervical cancer progression and its associated mechanism. Methods. Colony formation assay was employed to analyze the radio-resistance and proliferation of cervical cancer cells. Cell proliferation ability was also assessed by 5-ethynyl-2’-deoxyuridine (EdU) assay. Cell apoptosis was analyzed by flow cytometry. Tube formation assay was performed to analyze cell angiogenesis ability. Transwell assays were conducted to measure cell migration and invasion abilities. Dualluciferase reporter assay was utilized to verify the target relationships. Xenograft mice model was used to analyze the role of circ_0085616 in tumor growth in vivo. Results. Circ_0085616 expression was elevated in cervical cancer tissues and cell lines. Circ_0085616 interference suppressed the radio-resistance, proliferation, tube formation, migration, and invasion and elevated the apoptosis rate of cervical cancer cells. Circ_0085616 acted as a sponge for microRNA-541-3p (miR-541-3p), and miR-541-3p was negatively regulated by circ_0085616 in cervical cancer cells. Circ_0085616 absence-induced changes in the behaviors of cervical cancer cells were largely overturned by anti-miR-541- 3p. miR-541-3p negatively regulated ADP ribosylation factor like GTPase 2 (ARL2) expression by binding to its 3’ untranslated region (3’UTR). miR-541-3p mimicinduced effects were largely reversed by pcDNA-ARL2 in cervical cancer cells. Circ_0085616 positively regulated ARL2 expression by sequestering miR-541-3p. Circ_0085616 absence significantly inhibited the tumor growth in vivo. Conclusion. Circ_0085616 contributed to the radioresistance and progression of cervical cancer partly through mediating the miR-541-3p/ARL2 axis.
- PublicationOpen AccessClaudins as diagnostic and prognostic markers in gynecological cancer(Murcia : F. Hernández, 2009) Szabó, István; Kiss, András; Schaff, Zsuzsa; Sobel, GáborClaudins are the main protein components of tight junctions (TJs) which function as selective barriers by controlling paracellular diffusion, maintain cellular polarity and play a role in signal transduction. The expression pattern of the 24 known members of the claudin family proved to be organ and tissue specific. The up- or downregulation of individual claudins has been described, especially during carcinogenesis. A significant increase of claudins-1 and -7 was detected in premalignant cervical lesions and invasive cancer compared with normal cervical epithelia. Claudins-3 and -4 were elevated in endometrial cancer. Claudin-1 overexpression characterized type II (seropapillary) endometrial carcinoma, while claudin-2 was elevated in type I (endometrioid) carcinoma. Claudins-3 and -4 were highly expressed in serous ovarian carcinoma. The expression data on claudins in different premalignant and malignant alterations suggest that these proteins might serve as diagnostic and prognostic markers and might be targets for future therapy.
- PublicationOpen AccessExpression and hypermethylation of JAM and EPB41L3 in cervical squamous cell carcinoma: Clinical significance and applications(Universidad de Murcia. Departamento de Biología Celular e Histología, 2024) Gu, Yun; Chu, Chengzhuo; Yuan, Bei; Wang, Jiandong; Pan, ShiyangThis study aimed to explore the expression and hypermethylation of EPB41L3 and JAM3 in cervical squamous cell carcinoma (CSCC) and to investigate their clinical significance. JAM3 and EPB41L3 mRNA expression was analyzed using a public database, and protein expression was detected using immunohistochemistry. The methylation status of JAM3 and EPB41L3 was detected in CSCC tissues and cervical cytological specimens using a quantitative methylation-specific PCR (qMSP). JAM3 and EPB41L3 mRNA were downregulated in CSCC. The JAM3 protein was positively detected in 39.4% of CSCC tissues and frequently expressed in those with lower FIGO stage and no lymph node metastasis. EPB41L3 was expressed in 18.9% of CSCC tissues. The hypermethylation of JAM3 was detected in 52.3% of CSCC tissues and related to higher FIGO stage and lymph node metastasis. EPB41L3 hypermethylation was detected in 72.7% of CSCC tissues and related to older ages and lymph node metastasis. In cervical cytological specimens, no methylation of JAM3 and EPB41L3 was found in normal or inflamed cervical epithelial cells. The methylation of JAM3 was detected in 0%, 8.3%, and 6.3% of ASCUS, LSIL, and HSIL samples, while EPB41L3 was detected in 12.5%, 42.9%, and 71.4%, respectively. The sensitivity of the combination of JAM3 and EPB41L3 methylation detection in ASCUS, LSIL, and HSIL was 8.3%, 15.6%, and 85.7%, respectively. The specificity of the combination of JAM3 and EPB41L3 methylation detection was 100%. Downregulation of JAM3 and EPB41L3 by hypermethylation was detected in CSCC. JAM3 and EPB41L3 hypermethylation are potential biomarkers for cervical cancer screening.
- PublicationOpen AccessInhibitory effect of Curcumin on a cervical cancer cell line via the RAS/RAF signaling pathway(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Özdemır, İlhan; Zaman, Fuat; Baş, Dilek Doğan; Sari, Umut; Öztürk, Şamil; Tunce, Mehmet CudiObjective. Cervical cancer has a very important place in female infertility and ranks fourth among cancers affecting women. Curcumin (CUR) is closely associated with the expression and activity of various regulatory proteins. It is also known that curcumin has preventive and therapeutic effects on various types of cancer. In this study, the anticancer activities of curcumin were demonstrated in the human cervical cancer cell line (HeLa). Methods. qRT-PCR and western blot analyses were used to evaluate mRNA and protein expression of curcumin in HeLa and immortalized human skin keratinocyte cell lines (HaCaT) (proliferation and apoptosis regulatory markers of the RAS/RAF signaling pathway). MTT analysis was performed, showing HeLa and HaCaT cell proliferation depending on the dose and duration of curcumin and doxorubicin. A wound scratch healing assay was applied to examine cell migration and invasion of HeLa after curcumin application. To determine the role of curcumin and doxorubicin in the apoptosis of HeLa cells, the mRNA levels of caspase-3 were examined by qRT-PCR. The results were analyzed with a one-way ANOVA SPSS 20.0 program. Results. CUR (IC50: 242.8 μM) and DOX (IC50: 92.1 μM) were determined to have the ability to inhibit the proliferation of HeLa cells and induce apoptosis over a 72-hour period and dose-dependently. Moreover, the results revealed that the mRNA and protein expression levels of RAF and RAS in HeLa cells were downregulated by CUR and DOX. Conclusions. The findings show that an alternative treatment method for cervical cancer can be developed with the application of CUR and DOX. Alternative methods for cervical cancer treatment may be developed using different methods in future studies.
- PublicationOpen AccessInterleukin 6 receptor (IL-6R) was an independent prognostic factor in cervical cancer(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Luan, Shaohong; An, Zhijie; Bi, Shuna; Chen, Long; Fan, JunIL-6 has been found to be associated with poor response to chemoradiotherapy and poor overall prognosis of patients with cervical cancer. However, little is known about the clinicopathological significance of IL-6 receptor (IL-6R) expression in the setting of cervical cancer. To investigate the clinicopathological meaning of IL-6R in cervical cancer, expression of IL6R was detected using immunohistochemistry in cervical cancer tissue microarray composed of 98 cases of cervical cancer and paired normal controls. As further confirmation of expression trend, western-blotting was conducted in another independent 36 pairs of cervical cancer and matched normal controls. Subsequently, the statistical correlation between IL-6R expression and clinicopathological variables was analyzed, including demographic, TNM stage, clinical grading and overall prognosis. IL-6R expression was shown to be remarkably associated with lymph node metastasis, recurrence and overall prognosis. Moreover, only IL-6R expression was observed to be an independent prognostic factor among these variables that could potentially influence the overall prognosis of patients with cervical cancer. In conclusion, IL-6R was shown to be an independent prognostic factor for patients with cervical cancer.
- PublicationOpen AccessLncRNA CERS6-AS1, sponging miR-6838-5p, promotes proliferation and invasion in cervical carcinoma cells by upregulating FOXP2(Universidad de Murcia. Departamento de Biología Celular e Histología, 2023) Yan, Kun; Hu, Chunyan; Liu, Chen; Chu, Guanghua; Wang, Xinru; Ma, Shuyun; Li, LongCervical cancer (CC) is a common disease in women characterized by high recurrence rate. LncRNA ceramide synthase 6 antisense RNA 1 (CERS6-AS1) has been found to play a crucial role in the progression of breast cancer and pancreatic cancer. Nevertheless, the regulatory role of CERS6-AS1 in CC remains largely unclear. Here, we found that the expression of CERS6- AS1 was upregulated in CC tissues and cell lines compared with adjacent tissues and normal human cervical epithelial cells. CERS6-AS1 overexpression promoted proliferation and invasion, and inhibited apoptosis in CC cells, while silencing of CERS6-AS1 led to the opposite results. CERS6-AS1 was verified as a sponge of miR-6838-5p by RNA pull-down and luciferase reporter gene assays. Functional investigations revealed that CERS6-AS1 knockdown inhibited proliferation and invasion, and promoted apoptosis in CC cells, which was reversed by miR-6838-5p inhibitor. Furthermore, forkhead box P2 (FOXP2) was identified as a target for miR-6838-5p, and overexpression of miR6838-5p decreased the expression level of FOXP2. Besides, CERS6-AS1 was able to sponge miR-6838-5p to accelerate CC cell proliferation and invasion and inhibited cell apoptosis through upregulating FOXP2 expression. In general, CERS6-AS1 was able to regulate CC cell proliferation, invasion and apoptosis by the miR-6838-5p/FOXP2 axis, which suggested that CERS6-AS1 may be a potential target for the treatment of CC.
- PublicationOpen AccessmiR-638 suppresses cervical cancer progression by inhibiting NCAPG2 under the treatment of Tetrandrine(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Wang, Min; Liu, Kai; Zhou, Zhongming; Geng, HuizhuanBackground. The interaction of microRNA with Chinese herbal medicines is a promising therapeutic approach for prevention of cervical cancer. Methods. Western blotting or qRT-PCR were carried out to identify the expression of NCAPG2 and miR-638. A tetrandrine (TET) cell model was used to explore the effects of miR-638 and its target gene NCAPG2 using CCK-8, transwell, wound healing, and western blot assays. Furthermore, luciferase activity assay was conducted to measure the interaction among TET, NCAPG2 and miR-638. Results. Under TET treatment, Hela and SiHa cells exhibited repressed cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT), and these effects were further enhanced by high expression of miR-638. In contrast, NCAPG2 expression was low in TET-treated cells and had an opposite effect to that of miR-638. Conclusion. We highlighted that miR-638 suppresses cervical cancer progression by inhibiting NCAPG2 under tetrandrine treatment
- PublicationOpen AccessThe methyltransferase KIAA1429 potentiates cervical cancer tumorigenesis via modulating LARP1 mRNA m6A modification and stability(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Feng, Xi; Shu, Liuping; Biología Celular e HistologíaCervical cancer (CC) is one of the most common gynecological malignancies in the world and poses a great threat to public health. There is inadequate knowledge of the molecular mechanisms underlying CC. This study aimed to explore the prognostic value of KIAA1429 (VIRMA, vir-Like m6A methyltransferase associated) in patients with CC and analyze its molecular mechanisms. The level of KIAA1429 in tumor specimens was tested using RT-qPCR and western blotting. Cellular biological processes were assessed using CCK-8 and Transwell assays. Xenograft experiments were used to verify the function of KIAA1429 in CC in vivo. The results manifested that KIAA1429 expression was enhanced in CC. Downregulation of KIAA1429 hindered the viability, migration, and invasion of CC cells. Moreover, LARP1 (La-related protein 1) was uncovered to be positively modulated by KIAA1429. Further, the anti-tumor impacts of KIAA1429 depletion on the phenotype of CC cells were counteracted by LARP1 amplification. Additionally, KIAA1429 deficiency suppressed the stability of LARP1 through methylating LARP1. Collectively, KIAA1429 can boost the tumorigenesis of CC via modifying LARP1 through m6A methylation to promote its stability. This work highlights the promoting effects of KIAA1429 on CC development and presents new targets for its treatment.
- PublicationOpen AccessThe roles and clinical significance of microRNAs in cervical cancer(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Wang, Fenfen; Li, Baohua; Xie, XingCervical carcinogenesis induced by persistent human papillomavirus (HPV) infection represents a stepwise progression from precursors to invasive cervical cancer. Accumulated evidence has shown aberrant expression of microRNAs (miRNAs) in cervical cancer tissues and cells. Further studies reveal that miRNAs play key roles in the initiation and progression of cervical cancer, via specific signaling pathways, including E6-p53, E7-pRb, phosphoinositide3 kinase (PI3K)-Akt, Notch, Wnt/β-catenin, and Hedgehog pathways. Some studies demonstrate that miRNAs might serve as biomarkers or therapeutic targets, presenting a potential prospect in clinical practice. All results provide new insights into the function of miRNAs and the pathogenesis of cervical cancer induced by viral oncoproteins. New approaches for miRNA-based prevention and management for cervical cancer will be developed in the future.
- PublicationOpen AccessTissue microarray validation in cervical carcinoma studies. A methodological approach(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Lovane, Lucília; Carrilho, Carla; Karlsson, ChristinaTissue microarrays (TMAs) are a cost-effective tool to study biomarkers in clinical research. Cervical cancer (CC) is one of the most prevalent in women worldwide, with the highest prevalence in low-middle-income countries due to a lack of organized screening. CC is associated with persistent high-risk human papillomavirus infection. Several biomarkers have been studied for diagnostic, therapeutic, and prognostic purposes. We aimed to evaluate and validate the effectiveness of TMA in CC compared to whole slide images (WSs). We selected and anonymized twenty cases of CC. P16, cytokeratin 5 (CK5), cytokeratin 7 (CK7), programmed death-ligand 1 (PD-L1), and CD8 expression were immunohistochemically investigated. All WS were scanned and 10 representative virtual TMA cores with 0.6 mm diameter per sample were selected. Ten random combinations of 1-5 cylinders per case were assessed for each biomarker. The agreement of scoring between TMA and WS was evaluated by kappa statistics. We found that three cores of 0.6 mm on TMA can accurately represent WS in our setting. The Kappa value between TMA and WS varied from 1 for p16 to 0.61 for PD-L1. Our study presents an approach to address TMA sampling that could be generalized to TMA-based research, regardless of the tissue and biomarkers of interest.
- PublicationOpen AccessTranscription factor ZNF488 accelerates cervical cancer progression through regulating the MEK/ERK signaling pathway(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Weng, Kena; Li, Lu; Zhou, HaipingCervical cancer (CC) is one of the most common gynecological malignancies worldwide. Zinc Finger Protein 488 (ZNF488) has been identified as an oncogene in nasopharyngeal carcinoma. However, its biological role and potential mechanism in CC remain to be elucidated. In the present study, upregulation of ZNF488 expression in human CC tissues was found in clinical samples and analyzed in The Cancer Genome Atlas (TCGA) dataset, which was associated with clinical staging and lymph node metastasis. Quantitative real time polymerase chain reaction (PCR) and western blot assays indicated that the expression of ZNF488 was up-regulated in CC cells. Cell colony formation and cell cycle analysis assays suggested that ZNF488 promoted CC cell proliferation and cycle progression. Knockdown of ZNF488 inhibited tumor growth of xenograft tumor mice in vivo, in agreement with the levels of ZNF488 and Ki-67. Moreover, transwell and western assays demonstrated that ZNF488 enhanced CC cell migration and invasion. Additionally, knockdown of ZNF488 also inhibited lung metastasis of CC cells in vivo. Further mechanism analysis implied that ZNF488 promoted the MEK/ERK signaling pathway. ERK inhibitor PD98059 significantly weakened the proliferation and epithelialmesenchymal transformation (EMT) promotion effect of ZNF488. Collectively, ZNF488 exerts its oncogene function partially through modulating MEK/ERK signaling pathway in CC, indicating that ZNF488 may provide a promising therapeutic target for the treatment of CC.