Jun Wang

TPX2 Serves as a Cancer Susceptibility Gene and Is Closely Associated with the Poor Prognosis of Endometrial Cancer

Background. Endometrial cancer (EC) is a common tumor of the genital tract that affects the female reproductive system but with only limited treatment options. We aimed to discover new prognostic biomarkers for EC. Methods. We used mRNA-seq data to detect differentially expressed genes (DEGs) between EC and control tissues. Detailed clinicopathological information was collected, and changes in the mRNA and protein levels of hub DEGs were analyzed in EC. Copy number variation (CNV) was also evaluated for its association with the pathogenesis of EC. Gene set enrichment analysis (GSEA) was conducted to enrich significant pathways driven by the hub genes. Cox regression analysis was used to select variables to create a nomogram. The nomogram was calibrated by applying the concordance index (C-index), and net benefits of the nomogram at different threshold probabilities were quantified using decision curve analysis (DCA). Results. Differential expression analysis identified 24 DEGs as potential risk factors for EC. Survival analysis revealed that TPX2 expression was related to worsening overall survival in patients with advanced EC. A high CNV was associated with the overexpression of TPX2; this suggested that modifications in the cell-cycle pathway might be crucial in the advancement of EC. Moreover, an individualized nomogram was developed for TPX2 incorporating clinical factors; this was also evaluated for its ability to predict EC. Calibration and DCA analyses confirmed the robustness and clinical usefulness of the nomogram. Conclusion. We offer novel insights into the pathogenesis and molecular mechanisms of EC. The overexpression of TPX2 was related to a poorer prognosis and could serve as a biomarker for predicting prognostic outcomes in EC patients.

Cystathionine‐γ‐Lyase/Hydrogen Sulfide Axis Plays a Crucial Role in Promoting the Progression of Cervical Cancer

ABSTRACT The role of endogenous hydrogen sulfide (H 2 S) in the pathophysiological mechanisms of various organ tumors has been extensively studied; however, its relevance to cervical cancer remains unexplored. This study aimed to examine the effect of endogenous H 2 S and its main synthetic enzyme, cystathionine‐γ‐lyase (CSE), in regulating the growth behavior in cervical cancer cells. The proliferation, migration, and invasion of C33A and HeLa cervical cancer cells were investigated, followed by molecular, biochemical, and immunocytochemical analyses. The results indicated that CSE is highly expressed in C33A and HeLa cells and modulates the levels of endogenous H 2 S. CSE knockdown suppressed the proliferation, migration, and invasion of cervical cancer cells. The CSE‐mediated growth patterns involved epithelial–mesenchymal transition (EMT), mitochondrial apoptosis, pyroptosis, reactive oxygen species (ROS) production, and the PI3K/AKT/mTOR signaling pathway. Additionally, CSE knockdown inhibited the growth of xenograft tumors in vivo. Similarly, CSE overexpression was performed for reverse verification. In brief, inhibition of CSE reduced cervical cancer growth, while overexpression of CSE promoted it. These findings indicated that CSE may serve as a potential target for early diagnosis, prognosis assessment, and therapeutic intervention in cervical cancer.

Safety and efficacy of radical hysterectomy based on embryo development-originated in the treatment of early cervical cancer: a single-arm meta-analysis

Cervical cancer is the leading malignancy in terms of both incidence and mortality among cancers of the female reproductive system, and initial surgical treatment is still one of the main treatments. However, for many years, radical hysterectomy based on traditional anatomical principles has failed to substantially improve oncological outcomes for cervical cancer patients or reduce the incidence of perioperative complications. In recent years, radical surgery grounded in the membrane anatomy concept of embryonic development has demonstrated promising oncological outcomes in colorectal cancer surgery. Research in the field of cervical cancer, however, remains in its early stages, although it is steadily garnering increased attention. Consequently, this meta-analysis seeks to systematically assess the safety and efficacy of radical hysterectomy, rooted in embryonic developmental principles, for the treatment of early-stage cervical cancer. This study systematically searched PubMed, Embase, Cochrane Library, Web of Science, Wanfang, and CNKI databases for relevant studies published from their inception to October 2024. Data on 5-year recurrence-free survival (RFS), overall survival (OS), and surgical complications were collected for further analysis. Eight studies involving 1,226 patients were included in the meta-analysis. The surgical complication rate was 35.2%. Two studies reported a 5-year RFS of 86% and an OS of 88%. Radical hysterectomy based on embryo development-originated shows good safety and efficacy in treating early-stage cervical cancer. PROSPERO Identifier: CRD42024602098.

CircRNF144B/miR-342-3p/FBXL11 axis reduced autophagy and promoted the progression of ovarian cancer by increasing the ubiquitination of Beclin-1

AbstractCircular RNAs (circRNAs) can regulate autophagy and ovarian cancer (OC) progression. However, autophagy-associated circRNAs involved in OC progression are largely unknown. Bioinformatics, RNA sequencing, and qRT-PCR were conducted to detect circRNF144B expression in OC as well as its relationship with patient prognosis. Functional experiments were used to determine the effects of circRNF144B on the proliferation, mobility and autophagy of OC. Double luciferase reporter assays, immunoprecipitation, and ubiquitination detection were performed to determine the molecular mechanisms of circRNF144B in autophagy and OC progression. CircRNF144B was elevated in OC tissues with low autophagy levels, and associated with poor prognosis. CircRNF144B promoted the malignant biological properties of OC cells, and inhibited the autophagy. Mechanistically, circRNF144B acts as a sponge for miR-342-3p and inhibits miR-342-3p-induced degradation of lysine demethylase 2 A (FBXL11) mRNA, leading to elevated FBXL11 protein levels. Elevated FBXL11 promoted the ubiquitination and degradation of Beclin-1, thus inhibiting autophagy. In conclusion, CircRNF144B increased FBXL11 level by sponging miR-342-3p, whereas elevated FBXL11 promoted the ubiquitination and protein degradation of Beclin-1, thus suppressing autophagy flux and promoting OC progression. Thus, circRNF144B may be an effective target for OC therapy.

The SNP rs4846048 of MTHFR enhances the cervical cancer risk through association with miR‐522: A preliminary report

AbstractBackgroundThe present research was designed to explore the association between single nucleotide polymorphisms (SNPs) at the 3′‐untranslated region (3′‐UTR) of methylenetetrahydrofolate reductase (MTHFR) and the risk of cervical cancer (CC).MethodsFrom May 2015 to October 2016, a total of 197 patients (diagnosed with CC and precancerous lesions, and underwent surgical treatments) were enrolled in the study. Meanwhile, a total of 80 healthy cases were used as the controls. PCR‐DNA analysis was used to explore the genotype of the SNPs (rs4846048 and rs55763075) of the MTHFR 3′‐UTR as well as the association between allelic frequencies and the CC risk. Then, the role of rs4846048 SNPs in the association of microRNA‐522 (miR‐522) and MTHFR was evaluated through luciferase reporter assay. Meanwhile, the modulatory influence of miR‐522 on cell apoptosis and viability of Hela cells was also detected by flow cytometry and MTT assay.ResultsThe rs4846048 AG and G allele frequencies were significantly higher in CC subgroup compared with the control group. Methylenetetrahydrofolate reductase rs4846048 A/G alleles contributed to miR‐522 binding, and miR‐522 negatively modulated the expressions of MTHFR. Furthermore, miR‐522 overexpression increased cell viability but decreased apoptotic cells in Hela cells.ConclusionThe preliminary report revealed that the SNP rs4846048 of MTHFR enhanced the risk of CC through association with miR‐522, which further regulated cell viability and apoptosis in Hela cells.