Occurrence Of Cervical Cancer Research Articles

Long non-coding RNA NEAT1 promotes aerobic glycolysis and progression of cervical cancer through WNT/β-catenin/PDK1 axis.

Cervical cancer is one of the most common gynecological cancers. Accumulated evidence shows that long non-coding RNAs (lncRNAs) play essential roles in cervical cancer occurrence and progression, but their specific functions and mechanisms remain to be further explored. The RT-qPCR assay was used to detect the expression of NEAT1 in cervical cancer tissues and cell lines. CCK-8, colony formation, flow cytometry, western blotting, and Transwell assays were used to evaluate the impact of NEAT1 on the malignant behavior of cervical cancer cells. Glucose consumption, lactate production, ATP levels, ROS levels, MMP levels, and the mRNA expressions of glycolysis-related genes and tricarboxylic acid cycle-related genes were detected to analyze the effect of NEAT1 on metabolism reprograming in cervical cancer cells. The expressions of PDK1, β-catenin and downstream molecules of the WNT/β-catenin signaling pathway in cervical cancer cells and tissues were detected by western blotting, RT-qPCR, immunofluorescence and immunohistochemistry assays. This study investigated the role and possible molecular mechanism of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in cervical cancer. Our results showed that NEAT1 was highly expressed in cervical cancer tissues and cell lines. Downregulation of NEAT1 inhibited the proliferation, migration, invasion and glycolysis of cervical cancer cells, while overexpression of NEAT1 led to the opposite effects. Mechanistically, NEAT1 upregulated pyruvate dehydrogenase kinase (PDK1) through the WNT/β-catenin signaling pathway, which enhanced glycolysis and then facilitated cervical cancer metastasis. Furthermore, NEAT1 maintained the protein stability of β-catenin but did not affect its mRNA level. We also excluded the direct binding of NEAT1 to the β-catenin protein via RNA pull-down assay. The suppressive impact of NEAT1 knockdown on cell proliferation, invasion, and migration was rescued by β-catenin overexpression. The WNT inhibitor iCRT3 attenuated the carcinogenic effect induced by NEAT1 overexpression. In summary, these findings indicated that NEAT1 may contribute to the progression of cervical cancer by activating the WNT/β-catenin/PDK1 signaling axis.

The role of NF-κB in carcinogenesis of cervical cancer: opportunities and challenges.

The nuclear factor-κB (NF-κB) family, consisting of several transcription factors, has been implicated in the regulation of cell proliferation and invasion, as well as inflammatory reactions and tumor development. Cervical cancer (CC) results from long-term interactions of multiple factors, among which persistent high-risk human papillomavirus (hrHPV) infection is necessary. During different stages from early to late after HPV infection, the activity of NF-κB varies and plays various roles in carcinogenesis and progress of CC. As the center of the cell signaling transduction network, NF-κB can be activated through classical and non-classical pathways, and regulate the expression of downstream target genes involved in regulating the tumor microenvironment and acquiring hallmark traits of CC cells. Targeting NF-κB may help treat CC and overcome the resistance to radiation and chemotherapy. Even though NF-κB inhibitors have not been applied in clinical treatment as yet, due to limitations such as dose-restrictive toxicity and poor tumor-specificity, it is still considered to have significant therapeutic potential and application prospects. In this review, we focus on the role of NF-κB in the process of CC occurrence and hallmark capabilities acquisition. Finally, we summarize relevant NF-κB-targeted treatments, providing ideas for the prevention and treatment of CC.

The relationship between long non-coding gene CASC21 polymorphisms and cervical cancer

ABSTRACT Background CASC21 was reported to be a hotspot gene in cervical cancer. The relationship between CASC21 genetic polymorphisms and cervical cancer has not been reported. Genetic factors influence the occurrence of cervical cancer. Thus, we explored the correlation between CASC21 polymorphisms and cervical cancer. Methods A total of 973 participants within 494 cervical cancer cases and 479 healthy controls were recruited. Five single nucleotide polymorphisms (SNPs) in the CASC21 gene were genotyped using the Agena MassARRAY platform. Chi-squared test, logistic regression analysis, odds ratio (OR), multifactor dimensionality reduction (MDR), and 95% confidence interval (95%CI) were used for data analysis. Results In the overall analysis, rs16902094 (p = .014, OR = 1.86, 95% CI = 1.12–3.08) and rs16902104 (p = .014, OR = 1.86, 95% CI = 1.12–3.09) had the risk-increasing correlation with the occurrence of cervical cancer. Stratification analysis showed that rs16902094 and rs16902104 were still associated with cervical cancer risk in the subgroups with age > 51, BMI < 24 kg/m2, smokers, and patients with cervical squamous cell carcinoma. MDR analysis displayed that rs16902094 (.49%) and rs16902104 (.52%) were the main influential attribution factor for cervical cancer risk. Conclusion Our finding firstly determined that two CASC21 SNPs (rs16902094, rs16902104) were associated with an increased risk of cervical cancer, which adds to our knowledge regarding the effect of CASC21 on cervical carcinogenesis.

Social factors and age play a significant role in cervical cancer and advanced-stage disease among Danish women

BackgroundFor cervical cancer (CC), the implementation of preventive strategies has the potential to make cervical cancer occurrence and death largely avoidable. To better understand the factors possibly responsible for cervical cancer, we aimed to examine possible differences in age and social parameters as well as screening status between women with low- or high-stage cervical cancer and matched controls.MethodsThrough the Danish Cancer Registry (DCR), women diagnosed with cervical cancer in Denmark between 1987 and 2016 were included. These were age- and residence-matched in a 1:5 ratio with controls from the general female population. The study population was sub grouped into a low-stage subpopulation with women with early-stage cervical cancer and matched controls and a high-stage subpopulation with women with late-stage cervical cancer and matched controls. Age and social parameters were compared within the subpopulations as well as between low- and high-stage cases. For part of the study population, screening attendance was examined to compare differences in adherence.ResultsOverall, we found that the risk of cervical cancer is significantly increased in socially disadvantaged women and not least non-attenders in screening. Interestingly, the high-stage subpopulation was significantly older than the low-stage subpopulation (p < 0.001), and when examining the impact of age further, we found that for cervical cancer cases, the risk of having low-stage disease decreases significantly with increasing age, whereas the risk of having high-stage disease increases significantly with increasing age. In the screening cohort, significantly less cases than controls were attenders in screening with the most pronounced differences seen in the old subpopulation (women aged 50–64 years) and in the high-stage subpopulation (p-values all < 0.001). Interestingly, when examining the risk of CC for attenders and non-attenders, we demonstrated that many social parameters continue to influence the risk of cervical cancer, even in women attending screening.ConclusionsOlder women, socially disadvantaged women, and non-attenders in screening are particularly vulnerable in terms of developing cervical cancer, especially high-stage disease. Therefore, improvements in the participating rate in screening as well as a revision of the current screening guidelines are needed.

Comprehensive Analysis of the SUMO-related Signature: Implication for Diagnosis, Prognosis, and Immune Therapeutic Approaches in Cervical Cancer.

SUMOylation, an important post-translational protein modification, plays a critical role in cancer development and immune processes. This study aimed to construct diagnostic and prognostic models for cervical cancer (CC) using SUMOylation-related genes (SRGs) and explore their implications for novel clinical therapies. We analyzed the expression profiles of SRGs in CC patients and identified 15 SRGs associated with CC occurrence. After the subsequent qPCR verification of 20 cases of cancer and adjacent tissues, 13 of the 15 SRGs were differentially expressed in cancer tissues. Additionally, we identified molecular markers associated with the prognosis and recurrence of CC patients, based on SRGs. Next, a SUMOScore, based on SRG expression patterns, was generated to stratify patients into different subgroups. The SUMOScore showed significant associations with the tumor microenvironment, immune function features, immune checkpoint expression, and immune evasion score in CC patients, highlighting the strong connection between SUMOylation factors and immune processes. In terms of immune therapy, our analysis identified specific chemotherapy drugs with higher sensitivity in the subgroups characterized by high and low SUMOScore, indicating potential treatment options. Furthermore, we conducted drug sensitivity analysis to evaluate the response of different patient subgroups to conventional chemotherapy drugs. Our findings revealed enrichment of immune-related pathways in the low-risk subgroup identified by the prognostic model. In conclusion, this study presents diagnostic and prognostic models based on SRGs, accompanied by a comprehensive index derived from SRGs expression patterns. These findings offer valuable insights for CC diagnosis, prognosis, treatment, and immune-related analysis.

Human papillomavirus type 16 E7 promotes cell viability and migration in cervical cancer by regulating the miR-23a/HOXC8 axis

Background Human papillomavirus (HPV) is a risk factor for the occurrence of cervical cancer (CC). Here, we aimed to explore the role of HPV16 in CC and identify the underlying mechanism. Methods The expression of miR-23a, HPV16 E6/E7 and homeobox C8 (HOXC8) was measured by quantitative real-time PCR or western blot. Cell viability and migration were evaluated using cell counting kit-8, Transwell and wound healing assays. The targeting relationship between miR-23a and HOXC8 was revealed by dual-luciferase reporter assay. Results miR-23a was downregulated in HPV16-positive (HPV16+) CC tissues and HPV16+ and HPV18+ cells. Additionally, E6/E7 expression was increased in CC cells. Then, we found that E7, rather than E6, positively regulated miR-23a expression. miR-23a suppressed cell viability and migration, whereas E7 overexpression abrogated this suppression. miR-23a targeted HOXC8, which reversed miR-23a-mediated cell viability and migration. Conclusions HPV16 E7-mediated miR-23a suppressed CC cell viability and migration by targeting HOXC8, suggesting a novel mechanism of HPV-induced CC.

RACK1 promotes the occurrence and progression of cervical carcinoma.

RACK1 has been identified as a multifunctional cytosolic protein, and plays a pivotal role in multiple biological responses involved in several kinds of tumors, while its effect in cervical cancer has not been well elucidated yet. The study aimed to investigate the role of RACK1 in cervical cancer occurrence and progression. The expression of RACK1 in cervical specimens was measured by immunohistochemical staining and Western blot assay. Transgenic mice were used to detect the role of RACK1 in modulating tumorigenesis invivo. Cervical carcinoma cell lines were used to explore the underlying mechanisms of RACK1 on the behaviors of tumor cells invitro. We found that RACK1 expression was upregulated in cancer tissues compared with adjacent tissues, and its expression was gradually increased from cervictis, and cervical intraepithelial neoplasis (CIN) to carcinoma. Genetic overexpression of RACK1 facilitated tumor formation and growth in nude mice. Mechanism studies disclosed that RACK1 over-expression prolonged the G0 /G1 phase by up-regulating the expression of cyclinD1, down-regulating p21 and p27 probably by modulating the phosphorylation of AKT. Taken together, we concluded that RACK1 stimulates tumorigenesis and progression of cervical cancer via modulating the proliferation of tumor cells, implying that targeting RACK1 may serve as a promising method for cervical cancer therapy.

Exploring the causal association between rheumatoid arthritis and the risk of cervical cancer: a two-sample Mendelian randomization study

ObjectiveWhether rheumatoid arthritis patients have an increased risk of cervical cancer remains controversial, and further research is needed on this clinical question. This study aims to investigate the association between rheumatoid arthritis and the susceptibility to cervical cancer by employing Mendelian randomization methodology, utilizing the extensive dataset from human genome-wide association data analysis.MethodsThe publicly accessible MR base database was utilized to obtain the complete genome, relevant research findings, and summarized data pertaining to rheumatoid arthritis and cervical cancer. Genetic tool variables, specifically single-nucleotide polymorphisms closely linked to rheumatoid arthritis, were chosen for analysis. Four methods, namely inverse variance weighted analysis, weighted median analysis, weighted mode, and MR-Egger regression, were employed. Statistical analysis was conducted to explore the potential association between rheumatoid arthritis and susceptibility to cervical cancer.ResultsThe results of the inverse variance weighted analysis (OR = 1.096, 95% CI: 1.018–1.180, P = 0.015) indicate a significant causal relationship between rheumatoid arthritis and an increased risk of cervical cancer. Furthermore, the absence of horizontal pleiotropic effects (MR-Egger intercept = 0.00025, P = 0.574) and heterogeneity (QEgger = 2.239, I2Egger = 0.225, PEgger = 0.268, QIVW = 2.734, I2IVW = 0.220, PIVW = 0.999) suggests that the observed association is not influenced by confounding factors. Sensitivity analysis and other statistical methods also support the conclusion that genetic pleiotropy does not introduce bias to the findings.ConclusionThere is a causal relationship between rheumatoid arthritis and the occurrence of cervical cancer. People with rheumatoid arthritis is one of the high-risk groups for early screening of cervical cancer. The IL-18 may play a significant role in elevating the risk of cervical cancer among rheumatoid arthritis patients.

Chitosan-Functionalized Poly(β-Amino Ester) Hybrid System for Gene Delivery in Vaginal Mucosal Epithelial Cells.

Gene therapy displays great promise in the treatment of cervical cancer. The occurrence of cervical cancer is highly related to persistent human papilloma virus (HPV) infection. The HPV oncogene can be cleaved via gene editing technology to eliminate carcinogenic elements. However, the successful application of the gene therapy method depends on effective gene delivery into the vagina. To improve mucosal penetration and adhesion ability, quaternized chitosan was introduced into the poly(β-amino ester) (PBAE) gene-delivery system in the form of quaternized chitosan-g-PBAE (QCP). At a mass ratio of PBAE:QCP of 2:1, the polymers exhibited the highest green fluorescent protein (GFP) transfection efficiency in HEK293T and ME180 cells, which was 1.1 and 5.4 times higher than that of PEI 25 kD. At this mass ratio, PBAE-QCP effectively compressed the GFP into spherical polyplex nanoparticles (PQ-GFP NPs) with a diameter of 255.5 nm. In vivo results indicated that owing to the mucopenetration and adhesion capability of quaternized CS, the GFP transfection efficiency of the PBAE-QCP hybrid system was considerably higher than those of PBAE and PEI 25 kD in the vaginal epithelial cells of Sprague-Dawley rats. Furthermore, the new system demonstrated low toxicity and good safety, laying an effective foundation for its further application in gene therapy.

The difference of transcriptome of HPV-infected patients contributes more to the occurrence of cervical cancer than the mutations of E6 and E7 genes in HPV16.

Human papillomavirus (HPV) E6 and E7 genes are biomarkers and drivers of the progression of cervical cancer (CxCa). The aim of this study was to investigate the relationship between HPV16 E6, E7 gene mutations and the occurrence and development of CxCa. Cervical exfoliated cells and clinical data of patients with cervical diseases were collected. Sample DNA was extracted, the E6 and E7 gene fragments were amplified by PCR, and the mutations were detected by Sanger sequencing and compared with standard sequences. Microarray was used to sequence the transcriptome of cells. Data of transcriptome analyzed and visualized using R software and its packages. Analysis of clinical characteristics demonstrated the association of HPV16 infection with CxCa (P < .05). Sanger sequencing results showed that the mutation sites of E6 gene included T178G/A, T350G, A131C, and T241G; among these, A131C and T241G were synonymous mutations. The mutation sites of E7 gene included A647G, T846C, G666A, T843C, and T760C, and all of them were synonymous mutations except A647G. There was no significant difference in the distribution of HPV16 E6, E7 mutations among CxCa, cervical intraepithelial neoplasia, and infection groups (P > .05). Compared with the non- CxCa group, gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of differentially expressed genes (DEGs) showed more significant enrichment of DEGs in the biological processes, pathways, and diseases closely related to cancer. Compared with the non-mutation group, the DEGs in the E6, E7 gene mutation group were significantly enriched in the events related to infection and immunity. To summarize, HPV16 may be associated with the occurrence and development of CxCa, but HPV16 E6 and E7 gene mutations have little effect on the occurrence and development of CxCa. Individual differences may have a greater effect on the progression of CxCa.

HPV16 E6 Oncogene Contributes to Cancer Immune Evasion by Regulating PD-L1 Expression through a miR-143/HIF-1a Pathway.

Human Papillomaviruses have been associated with the occurrence of cervical cancer, the fourth most common cancer that affects women globally, while 70% of cases are caused by infection with the high-risk types HPV16 and HPV18. The integration of these viruses' oncogenes E6 and E7 into the host's genome affects a multitude of cellular functions and alters the expression of molecules. The aim of this study was to investigate how these oncogenes contribute to the expression of immune system control molecules, using cell lines with integrated HPV16 genome, before and after knocking out E6 viral gene using the CRISPR/Cas9 system, delivered with a lentiviral vector. The molecules studied are the T-cell inactivating protein PD-L1, its transcription factor HIF-1a and the latter's negative regulator, miR-143. According to our results, in the E6 knock out (E6KO) cell lines an increased expression of miR-143 was recorded, while a decrease in the expression of HIF-1a and PD-L1 was exhibited. These findings indicate that E6 protein probably plays a significant role in enabling cervical cancer cells to evade the immune system, while we propose a molecular pathway in cervical cancer, where PD-L1's expression is regulated by E6 protein through a miR-143/HIF-1a axis.

Factors influencing HPV vaccine implementation in South Asia: a scoping review protocol

IntroductionThe HPV vaccine is characterized by its significant effectiveness in preventing the occurrence of cervical cancer. However, the South Asian countries face multiple challenges in implementing the human papillomavirus vaccine (HPV) at scale. Implementation of human papillomavirus vaccination for eliminating cervical cancer necessitates investigating the factors that impact the health system of these nations. Hence, this review will map the evidence on factors influencing the scaling up of human papillomavirus vaccination in South Asia.MethodsThe proposed scoping review will follow the steps given by Arksey and O’Malley and Levac et al. The search approach will follow McGowan et al. (14) evidence-based manual for Peer Analysis of Electronic Search Strategies (PRESS 2015) for systematic searches. Using a comprehensive search, the literature from 2006 onward will be identified from PubMed, CINAHL, EMBASE, Web of Science, and Scopus. The search strategy will include terms relating to the HPV vaccine and implementation. A predefined criterion for the inclusion and exclusion of studies will be adopted by three review authors independently to determine the eligible studies. The results will be narratively synthesized and examined in addition to being quantitatively presented to provide an outline. The review will be presented per the “Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review (PRISMA-ScR)” guidelines.Conclusions/discussionThe evaluation is anticipated to map the barriers and enablers influencing the rollout of the human papillomavirus vaccine. Lessons learned from the South Asian countries, where the vaccine has been implemented, may contribute to aiding the implementation of the vaccine in countries with similar health systems in an effective manner.Systematic review registrationThe protocol was prospectively registered on the “open science framework”. The registration DOI is https://doi.org/10.17605/OSF.IO/T5SW9.

Multiple HPV integration mode in the cell lines based on long-reads sequencing.

The integration of human papillomavirus (HPV) is closely related to the occurrence of cervical cancer. However, little is known about the complete state of HPV integration into the host genome. In this study, three HPV-positive cell lines, HeLa, SiHa, and CaSki, were subjected to NANOPORE long-read sequencing to detect HPV integration. Analysis of viral integration patterns using independently developed software (HPV-TSD) yielded multiple complete integration patterns for the three HPV cell lines. We found distinct differences between the integration patterns of HPV18 and HPV16. Furthermore, the integration characteristics of the viruses were significantly different, even though they all belonged to HPV16 integration. The HPV integration in the CaSki cells was relatively complex. The HPV18 integration status in HeLa cells was the dominant, whereas the percentage of integrated HPV 16 in SiHa and CaSki cells was significantly lower. In addition, the virus sequences in the HeLa cells were incomplete and existed in an integrated state. We also identified a large number of tandem repeats in HPV16 and HPV18 integration. Our study not only clarified the feasibility of high-throughput long-read sequencing in the study of HPV integration, but also explored a variety of HPV integration models, and confirmed that viral integration is an important form of HPV in cell lines. Elucidating HPV integration patterns will provide critical guidance for developing a detection algorithm for HPV integration, as well as the application of virus integration in clinical practice and drug research and development.

Hsa_Circ_0000021 Sponges miR-3940-3p/KPNA2 Expression to Promote Cervical Cancer Progression.

Circular RNAs (circRNAs) have a vital role in the occurrence of numerous cancers. However, its function and pattern of expression in cervical cancer (CC) remain unclear. This research aims to investigate the hsa_circ_000002's regulatory mechanism in CC. Hsa_circ_0000021, miR-3940-3p, and KPNA2 expression levels were estimated through qRT-PCR. Nuclear/cytoplasmic separation was conducted to find the subcellular location of hsa_circ_0000021. Western blot was done to estimate the levels of KPNA2 protein. CCK-8, BrdU, wound healing, transwell, and tumor xenograft assays were performed to study how hsa_circ_0000021/miR-3940-3P/KPNA2 function affect CC. Hsa_circ_0000021's targeting relationships with miR-3940-3p and KPNA2 were ascertained through RIP and luciferase experiments. Hsa_circ_0000021 and KPNA2 were overexpressed and inversely associated with the levels of miR-3940-3p in CC. Knocking down either hsa_circ_0000021 or KPNA2 repressed the growth of CC tumors as well as the proliferation, invasion, and migration of CC cells. Silencing miR-3940-3p promoted the malignant proliferation of CC cells. Regarding its mechanism, hsa_circ_0000021 affected the malignant CC cell proliferation via the sponging of miR-3940-3p, which targeted KPNA2. Hsa_circ_0000021 regulates the miR-3940-3p/KPNA2 axis to promote CC occurrence. This potentially is a novel target for CC treatment.

Association between family income to poverty ratio and HPV infection status among U.S. women aged 20 years and older: a study from NHANES 2003-2016.

HPV infection is closely related to the occurrence of cervical cancer and has an important adverse effect on human life and health. This study used data from the NHANES 2003-2016 to investigate the relationship between PIR and HPV infection status among Americans aged 20 and older. The data for this cross-sectional investigation came from the 2003-2016 National Health and Nutrition Examination Survey (NHANES), which included 9580 women who were 20 years of age or older. The linear and nonlinear correlations between PIR and the presence of HPV infection were investigated using multiple linear regression and smooth curve fitting. The stability of the relationship across groups was examined using subgroup analysis and interaction tests. There were 2232 impoverished homes and 2543 rich households among the 9580 adult participants aged 20 and above. PIR (ratio of income to poverty) was found to be significantly inversely related to the presence of HPV infection [0.91 (0.89, 0.94)] after adjusting for all other covariates, and the trend persisted even after categorizing PIR into high- and low-income groups (PIR>4 and PIR<1). In addition, significant negative relationships were discovered in subgroup analyses for women aged 25 to 59 [0.90 (0.88, 0.93)], non-Hispanic whites [0.80 (0.70, 0.92)], non-diabetics [0.91 (0.88, 0.94)], and those who had ever engaged in sex [0.91 (0.89, 0.94)]. PIR was highly and negatively correlated with the presence of HPV infection in American women aged 20 and older. The results of this study are of great significance for preventing HPV infection and improving the accuracy of HPV screening.

Role of extracellular vesicle in human papillomavirus-associated cervical cancer.

Cervical cancer is a gynecological malignant tumor and a serious threat to women's health. Although human papillomavirus (HPV) infection and the occurrence of cervical cancer are known to be closely related, the underlying carcinogenic mechanism of HPV is not fully understood. Extracellular vesicles (EVs) are found in a variety of body fluids and play an important role in both intercellular communication and cancer progression. Furthermore, the presence of EVs makes liquid biopsy of cervical cancer possible. The study of EVs in cervical cancer can provide clinical ideas for the diagnosis and treatment of the disease. The purpose of this article is to summarizes the role of EV contents in HPV-associated cervical cancer and discusses the possible clinical application of EVs in cervical cancer treatment. The search terms included the following: HPV with cervical cancer and extracellular vesicles. The initial literature search ended on March 1, 2023. In HPV-positive cervical cancer, EV contents are changed due to the presence of HPV. HPV-positive cervical cancer affects the cell microenvironment and other surrounding cells through the secretion of EVs.

SNORD6 promotes cervical cancer progression by accelerating E6-mediated p53 degradation

Small nucleolar RNAs (snoRNAs) are a class of non-coding RNAs widely distributed in eukaryotic nucleoli. In recent years, studies have revealed that snoRNAs can also participate in the occurrence and development of malignant tumors through different pathways. Cervical cancer is one of the most common malignant tumors of the female reproductive system, and the high-risk HPV virus infection is its main pathogenic mechanism. However, the outcomes in different patients with malignant tumors vary, indicating that other factors might affect the pathogenic process of cervical cancer. In this study, we screened the poor prognosis indicator SNORD6 from the TCGA database to find the snoRNA that affects the disease outcome during the pathogenesis of cervical cancer. We discovered that SNORD6 expression in cervical cancer tissues was higher than that in normal cervical tissues. Cell phenotype experiments revealed that the knockdown of SNORD6 retarded cell proliferation and plate clone formation. Furthermore, G1-S phase cell cycle arrest was induced, DNA synthesis was decreased, cell migration and invasion were reduced, while the level of apoptosis increased, whereas the opposite results were obtained after SNORD6 overexpression. Moreover, after intratumoral injection of ASO-SNORD6, the tumor growth rate slowed down, and the tumor volume decreased compared with the control group. In the mechanism study, we found that SNORD6 concurrently acted as a binding “hub” to promote the formation of the tumor suppressor protein p53 degradation complex E6-E6AP-p53. This reaction enhanced the ubiquitination and degradation of p53, thus influenced the regulation of p53 activities in the cell cycle and apoptosis. This study preliminarily clarified the biological role and specific mechanism of SNORD6 in the occurrence of cervical cancer, broadening the basic theoretical research of ovarian cancer and may provide a new perspective on the diagnosis and treatment of cervical cancer.

Elevated risk of cervical cancer in elderly women with incident ulcerative colitis in South Korea

The association between ulcerative colitis (UC) and uterine cervical cancer is still unclear. To investigate cervical cancer risk in South Korean women with UC, we analyzed the Korean National Health Insurance claims data. UC was defined using both ICD-10 codes and UC-specific prescriptions. We analyzed incident cases of UC diagnosed between 2006 and 2015. Age-matched women without UC (control group) were randomly selected from the general population (1:3 ratio). Hazard ratios were calculated using multivariate Cox proportional hazard regression, and the event was defined as occurrence of cervical cancer. A total of 12,632 women with UC and 36,797 women without UC were enrolled. The incidence of cervical cancer was 38.8 per 100,000 women per year in UC patients and 25.7 per 100,000 women per year in controls, respectively. The adjusted HR for cervical cancer was 1.56 (95% CI 0.97–2.50) in the UC group with reference to the control group. When stratified by age, the adjusted HR for cervical cancer was 3.65 (95% CI 1.54–8.66) in elderly UC patients (≥ 60 years) compared to elderly control group (≥ 60 years). Within UC patients, increased age (≥ 40 years) and low socioeconomic status were associated with an increased risk of cervical cancer. The incidence of cervical cancer was found to be higher among elderly patients (≥ 60 years) with newly diagnosed UC in South Korea, compared to age-matched controls. Therefore, regular cervical cancer screening is recommended for elderly patients who have recently been diagnosed with UC.

Curcumin suppressed the proliferation and apoptosis of HPV-positive cervical cancer cells by directly targeting the E6 protein.

Most human papillomavirus (HPV) types, including HPV16 and HPV18, are closely related to the occurrence of cervical cancer, predominantly through the action of viral oncoproteins E6 and E7. Curcumin, the active ingredient of the turmeric plant, has been gaining attention over the past two decades as an antioxidant, anti-inflammatory, and anticancer agent. In the present study, the HPV-positive cervical cancer cells HeLa and CaSki were treated with curcumin, and the results showed that curcumin has a dose-dependent and time-dependent inhibitory effect on cell viability. In addition, apoptosis induction was further quantitatively confirmed through flow cytometric analysis. Furthermore, the influence of different concentrations of curcumin on the mitochondrial membrane potential was evaluated through JC-1 staining and found to dramatically decrease the membrane potential in treated HeLa and CaSki cells, suggesting the critical role of the mitochondrial pathway in their apoptosis-inducing effect. This study also demonstrated the wound-healing potential of curcumin, and the results of transwell assays showed that curcumin treatment inhibited HeLa and CaSki cell invasion and migration in a dose-dependent manner compared with the control treatment. Curcumin also downregulated the expression of Bcl-2, N-cadherin, and Vimentin and upregulated the expression of Bax, C-caspase-3, and E-cadherin in both cell lines. Further research showed that curcumin also selectively inhibited the expression of the viral oncoproteins E6 and E7, as demonstrated by western blot analysis; moreover, the downregulation of E6 was more significant than that of E7. Our research also showed that coculture with cells infected with siE6 lentivirus (siE6 cells) can inhibit the proliferation, invasion, and metastasis of HPV-positive cells. While the siE6 cells were also treated with curcumin, the effect of curcumin monotherapy was offset. In summary, our research shows that curcumin regulates the apoptosis, migration, and invasion of cervical cancer cells, and the mechanism may be related to its ability to downregulate E6. This study provides a foundation for future research on the prevention and treatment of cervical cancer.

Direct Virus Gene Detection: A CRISPR/dCas9-Mediated Surface-Enhanced Raman Scattering Strategy with Enzyme-Catalyzed Signal Amplification.

The aberrant growth of cervical cells caused by the infection of human papillomavirus (HPV) may cause cervical cancer. In order to effectively prevent the occurrence of cervical cancer and for better follow-up treatment after surgery, a rapid and reliable detection method of HPV DNA is essential. Here, a surface-enhanced Raman scattering (SERS) detection method was developed based on the clustered regularly interspaced short palindromic repeats (CRISPR)/dCas9 technique and the enzyme catalysis amplification reaction, which achieved a simple and rapid detection of low-content HPV genes. The CRISPR/dCas9/sgRNA complex was anchored above a magnetic bead, which can precisely capture target DNA sequences, exhibiting high selectivity for HPV genes. When the biotinylated target DNAs exist, they can bridge a streptavidin-modified horse radish peroxidase (HRP) to the magnetic bead, producing an HRP-decorated conjugate. This conjugate allows an HRP-catalyzed reaction for its substrate (3,3',5,5'-tetramethylbenzidine, TMB). Gold nanostars with a silica shell exhibiting the lightning rod effect of SERS were employed to measure the SERS spectra of the oxidative product of TMB. Enzyme catalysis and SERS co-contribute to the SERS signal output, ensuring a high detection sensitivity. This method is a proof of concept for detecting HPV DNAs in a complex system. The current method can be applied to other target DNAs simply by changing the sgRNA sequence. Many superiors portend that the CRISPR/dCas9-based SERS method is promising for further clinical application.