Challenges in the Diagnosis and Individualized Treatment of Cervical Cancer

Schubert, Melanie; Bauerschlag, Dirk; Muallem, Mustafa Zelal; Maass, Nicolaì; Alkatout, İbrahim

doi:10.3390/medicina59050925

Cited by 10 publications

(3 citation statements)

References 67 publications

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“…Over 111,820 new cases and 13,740 cervical cancer deaths are estimated to occur in 2022 [ 36 ]. However, effective therapies for this deadly disease are limited because the elaborate molecular mechanism underlying cervical cancer progression remains unknown [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

“…With the development of vaccines and screening technologies, the incidence of cervical diseases has begun to decline in some countries [ 2 ]. However, extensive implementation has been restricted by economic factors and regional medical conditions [ 3 ]. The high incidence of carcinoma in situ is between 30 and 35 years old, and that of invasive cancer is between 45 and 55 years old, with a tendency of rejuvenation in recent years [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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KLF5 inhibits the migration and invasion in cervical cancer cell lines by regulating SNAI1

Qu,

Xu,

Yang

et al. 2024

CBM

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BACKGROUND: Epithelial-mesenchymal transition (EMT) is an important biological process by which malignant tumor cells to acquire migration and invasion abilities. This study explored the role of KLF5 in the EMT process of in cervical cancer cell lines. OBJECTIVE: Krüpple-like factor 5 (KLF5) is a basic transcriptional factor that plays a key role in cell-cycle arrest and inhibition of apoptosis. However, the molecular mechanism by which KLF5 mediates the biological functions of cervical cancer cell lines has not been elucidated. Here, we focus on the potential function of ELF5 in regulating the EMT process in in vitro model of cervical cancer cell lines. METHOD: Western-blot and real-time quantitative PCR were used to detect the expression of EMT-related genes in HeLa cells. MTT assays, cell scratch and Transwell assays were used to assess HeLa cells proliferation and invasion capability. Using the bioinformatics tool JASPAR, we identified a high-scoring KLF5-like binding sequence in the SNAI1 gene promoter. Luciferase reporter assays was used to detect transcriptional activity for different SNAI1 promoter truncates. RESULT: After overexpressing the KLF5 gene in HeLa cells, KLF5 not only significantly inhibited the invasion and migration of HeLa cells, but also increased the expression of E-cadherin and decreased the expression of N-cadherin and MMP9. In addition, the mRNA expression of upstream regulators of E-cadherin, such as SNAI1, SLUG, ZEB1/2 and TWIST1 was also decreased. Furthermore, KLF5 inhibiting the expression of the SNAI1 gene via binding its promoter region, and the EMT of Hela cells was promoted after overexpression of the SNAI1 gene. CONCLUSION: These results indicate that KLF5 can downregulate the EMT process of HeLa cells by decreasing the expression of the SNAI1 gene, thereby inhibiting the migration and invasion of HeLa cervical cancer cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

KLF5 inhibits the migration and invasion in cervical cancer cell lines by regulating SNAI1

Qu,

Xu,

Yang

et al. 2024

CBM

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“…Eighty percent of sexually active women become infected with HPV during their lifetime, but the infection persists in only 5-10 % of those initially infected and leads to cervical cancer in only 3 % (Schubert et al, 2023). In the absence of a clearly persistent HPV infection, the risk of developing cervical cancer is extremely low.…”

Section: Introductionmentioning

confidence: 99%

mRNA-lncRNA gene expression signature in HPV-associated neoplasia and cervical cancer

Kulaeva,

Muzlaeva,

Mashkina

2024

Vestn. VOGiS

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Cervical cancer is one of the most frequent cancers in women and is associated with human papillomavirus (HPV) in 70 % of cases. Cervical cancer occurs because of progression of low-differentiated cervical intraepithelial neoplasia through grade 2 and 3 lesions. Along with the protein-coding genes, long noncoding RNAs (lncRNAs) play an important role in the development of malignant cell transformation. Although human papillomavirus is widespread, there is currently no well-characterized transcriptomic signature to predict whether this tumor will develop in the presence of HPV-associated neoplastic changes in the cervical epithelium. Changes in gene activity in tumors reflect the biological diversity of cellular phenotype and physiological functions and can be an important diagnostic marker. We performed comparative transcriptome analysis using open RNA sequencing data to assess differentially expressed genes between normal tissue, neoplastic epithelium, and cervical cancer. Raw data were preprocessed using the Galaxy platform. Batch effect correction, identification of differentially expressed genes, and gene set enrichment analysis (GSEA) were performed using R programming language packages. Subcellular localization of lncRNA was analyzed using Locate-R and iLoc-LncRNA 2.0 web services. 1,572 differentially expressed genes (DEGs) were recorded in the “cancer vs. control” comparison, and 1,260 DEGs were recorded in the “cancer vs. neoplasia” comparison. Only two genes were observed to be differentially expressed in the “neoplasia vs. control” comparison. The search for common genes among the most strongly differentially expressed genes among all comparison groups resulted in the identification of an expression signature consisting of the CCL20, CDKN2A, CTCFL, piR-55219, TRH, SLC27A6 and EPHA5 genes. The transcription level of the CCL20 and CDKN2A genes becomes increased at the stage of neoplastic epithelial changes and stays so in cervical cancer. Validation on an independent microarray dataset showed that the differential expression patterns of the CDKN2A and SLC27A6 genes were conserved in the respective gene expression comparisons between groups.

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HPV18 E6/E7 activates Ca²⁺ influx to promote the malignant progression of cervical cancer by inhibiting Ca²⁺ binding protein 1 expression

Kang,

Qiu,

Duo

et al. 2024

Biotech and App Biochem

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Mounting studies have shown that the oncoproteins E6 and E7 encoded by the human papillomavirus (HPV) genome are essential in HPV‐induced cervical cancer (CC). Ca2+ binding protein 1 (CABP1), a downstream target of HPV18‐positive HeLa cells that interferes with E6/E7 expression, was identified through screening the GEO Database (GSE6926). It was confirmed to be down‐regulated in CC through TCGA prediction and in vitro detection. Subsequent in vitro experiments revealed that knocking down E6/E7 inhibited cell proliferation, migration, and invasion, whereas knocking down CABP1 promoted these processes. Simultaneously knocking down CABP1 reversed these effects. Additionally, the results were validated in vivo. Previous studies have indicated that CABP1 can regulate Ca2+ channels, influencing Ca2+ influx and tumor progression. In this study, it was observed that knocking down CABP1 enhanced Ca2+ inflow, as demonstrated by flow cytometry and confocal microscopy. Knocking down E6/E7 inhibited these processes, whereas simultaneously knocking down E6/E7 and CABP1 restored the inhibitory effect of knocking down E6/E7 on Ca2+ inflow. To further elucidate that E6/E7 promotes CC progression by inhibiting CABP1 expression and activating Ca2+ influx, BAPTA/AM treatment was administered during CABP1 knockdown. It was discovered that Ca2+ chelation could reverse the effect of CABP1 knockdown on CC cells. In conclusion, our results offer a novel target for the diagnosis and treatment of HPV‐induced CC.

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Challenges in the Diagnosis and Individualized Treatment of Cervical Cancer

Cited by 10 publications

References 67 publications

KLF5 inhibits the migration and invasion in cervical cancer cell lines by regulating SNAI1

KLF5 inhibits the migration and invasion in cervical cancer cell lines by regulating SNAI1

mRNA-lncRNA gene expression signature in HPV-associated neoplasia and cervical cancer

HPV18 E6/E7 activates Ca²⁺ influx to promote the malignant progression of cervical cancer by inhibiting Ca²⁺ binding protein 1 expression

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Challenges in the Diagnosis and Individualized Treatment of Cervical Cancer

Cited by 10 publications

References 67 publications

KLF5 inhibits the migration and invasion in cervical cancer cell lines by regulating SNAI1

KLF5 inhibits the migration and invasion in cervical cancer cell lines by regulating SNAI1

mRNA-lncRNA gene expression signature in HPV-associated neoplasia and cervical cancer

HPV18 E6/E7 activates Ca2+ influx to promote the malignant progression of cervical cancer by inhibiting Ca2+ binding protein 1 expression

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HPV18 E6/E7 activates Ca²⁺ influx to promote the malignant progression of cervical cancer by inhibiting Ca²⁺ binding protein 1 expression