Na Li

Circ_0044362 Facilitates the Progression of Epithelial Ovarian Cancer via Enhancing HOXB4 Transcription to Activate the RUNX1/IGFBP3 Axis

ABSTRACTIncreasing numbers of studies have elucidated the emerging roles of circular RNA (circRNA) in cancer progression. However, the function of circRNAs in modulating their parental genes in ovarian cancer remains poorly understood. In this study, we identified that circ_0044362, a circRNA derived from homeobox B4 (HOXB4), significantly promotes the expression of its parental gene HOXB4 in ovarian cancer. Functionally, circ_0044362 promotes the malignant phenotypes of ovarian cancer cells. Further analysis revealed that circ_0044362 facilitates the transcriptional activation of its parental gene HOXB4 by directly guiding U1 small nuclear ribonucleoprotein (snRNP) to its promoter region, thereby enhancing the oncogenic behaviors of ovarian cancer cells. Furthermore, HOXB4 positively regulates runt‐related transcription factor 1 (RUNX1) expression, with RUNX1 serving as a transcription factor to promote the transcription of insulin‐like growth factor binding protein‐3 (IGFBP3). Notably, inhibitors of either HOXB4, RUNX1, or IGFBP3 could reverse the oncogenic activity mediated by circ_0044362. Collectively, our findings reveal the involvement of the circ_0044362/HOXB4 pathway in ovarian cancer progression and provide potential therapeutic strategies for ovarian cancer treatment.

YBX2 modulates mRNA stability via interaction with YTHDF2 in endometrial cancer cells

RNA-binding proteins (RBPs) fine-tune gene expression by modulating RNA stability, translation, and degradation. RBPs are involved in the development of endometrial cancer. In particular, Y-box-binding protein 2 (YBX2), a germ cell-specific member of the YBX family, has been reported to maintain cancer stem cell-like phenotypes in endometrial cancer. However, the mechanism by which YBX2 modulates mRNA stability in endometrial cancer cells remains unknown. In this study, we examined the effects of the ectopic expression of YBX2 in endometrial adenocarcinoma-derived Ishikawa cells. We found that elevated levels of YBX2 delayed cell proliferation, without increasing cell apoptosis. Transcriptomic analysis revealed disturbances in gene expression caused by YBX2. Interestingly, heat shock protein family A (Hsp70) member 6 (HSPA6) levels were downregulated due to the reduced mRNA stability after YBX2 binding. YBX2 facilitated the formation of relatively stable cytoplasmic granules in tumor cells via its mRNA binding domain. Moreover, N

Alternative splicing of PSMD13 mediated by genetic variants is significantly associated with endometrial cancer risk

Accumulating evidence has shown that aberrant alternative splicing events are closely associated with the onset and development of cancer. However, whether genetic variants-associated alternative splicing is linked to risk of endometrial cancer remains largely uncertain. We identified single nucleotide polymorphisms (SNPs) locates in the splicing number trait locus (sQTL) of endometrial cancer using the CancerSplicing QTL database. In parallel with bioinformatics analysis, we conducted a case-control study comprising 2,000 cases and 2,013 controls to assess the association between identified SNP which possesses mRNA splicing function and endometrial cancer susceptibility. Furthermore, we used the Kaplan-Meier Plotter, The Human Protein Atlas, SPNR, and Spliceman2 databases for sQTL and differential gene expression analyses to identify the genetic variant which most potentially influence the risk of endometrial cancer through alternative splicing to reveal the potential mechanism by which candidate SNPs regulate the risk of endometrial cancer. The results indicated that SNP rs7128029 A<G was significantly associated with an increased risk of endometrial cancer (odds ratio=1.384; 95% confidence interval=1.038-1.964). Moreover, the carcinogenic effect of SNP rs7128029 A<G was consistently revealed by propensity matching analysis, an additive model, and a dominant model. Importantly, sQTL analysis showed that SNP rs7128029 could affect the transcriptional modification of These findings suggest that SNP rs7128029-mediated alternative splicing events in

Self-Assembling Amphiphilic Peptides Target the VDAC1-Hexokinase-II Complex to Induce Apoptosis in Cervical Carcinoma Cells

VDAC1, an outer mitochondrial membrane protein overexpressed in cancers, regulates apoptosis by interacting with antiapoptotic proteins and releasing apoptotic factors. We investigate novel multiblock cationic peptide amphiphiles targeting the VDAC1-Hexokinase-II complex in the mitochondria of cervical carcinoma cells. Amphiphilic peptide variants were designed by modifying the C-terminus of VDAC1 fragment LP1 with a cationic hydrophilic segment and the N-terminus with a hydrophobic domain, enabling self-assembly into nanofiber-like structures at elevated concentrations. In HeLa cells, these peptides triggered mitochondrial-mediated apoptosis through a decrease of the mitochondrial membrane potential, cytochrome

Identification of N1 methyladenosine‐related biomarker predicting overall survival outcomes and experimental verification in ovarian cancer

AbstractAimThis study aimed to construct a N1‐methyladenosine (m1A)‐related biomarker model for predicting the prognosis of ovarian cancer (OVCA).MethodsOVCA samples were clustered into two subtypes using the Non‐Negative Matrix Factorization (NMF) algorithm, including TCGA (n = 374) as the training set and GSE26712 (n = 185) as the external validation set. Hub genes, which were screened to construct a risk model, and nomogram to predict the overall survival of OVCA were explored and validated through various bioinformatic analysis and quantitative real‐time PCR.ResultsFollowing bootstrap correction, the C‐index of nomogram was 0.62515, showing reliable performance. The functions of DEGs in the high‐ and low‐risk groups were mainly enriched in immune response, immune regulation, and immune‐related diseases. The immune cells relevant to the expression of hub genes were explored, for example, Natural Killer (NK) cells, T cells, activated dendritic cells (aDC).ConclusionsAADAC, CD38, CACNA1C, and ATP1A3 might be used as m1A‐related biomarkers for OVCA, and the nomogram labeled with m1A for the first time had excellent performance for predicting overall survival in OVCA.

Unilateral cystectomy and serous histology are associated with relapse in borderline ovarian tumor patients with fertility-sparing surgery: a systematic review and meta-analysis

Surgical procedures, histological subtypes, and surgical approaches are involved in the recurrence of borderline ovarian tumors (BOTs), but whether those three factors affect relapse remains controversial. This study aimed to explore the effects of surgical procedures, histological subtypes, and surgical approaches on the relapse and pregnancy rates of BOT after fertility-preserving surgery (FPS) according to the patients' characteristics. A systematic search of PubMed, Embase, and the Cochrane library was conducted from their inception to November 2018. Studies that investigated the impact of surgical procedures, histological subtypes, and surgical approaches on the relapse and pregnancy rates in patients with BOT after FPS were eligible. The pooled odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated using the random-effects model. Thirty-five studies involving a total of 2921 patients with BOT after FPS were included. The pooled ORs indicated that the risk of relapse was significantly increased in patients who underwent unilateral cystectomy or with serous BOT. There was no significant difference between laparoscopy and laparotomy on the risk of relapse. Surgical procedures, histological subtypes, and surgical approaches did not influence pregnancy rates. Patients who underwent unilateral cystectomy or with serous BOT presented an excess risk of relapse after FPS, but the surgical approach did not affect the risk of relapse. The pregnancy rate is not affected by surgical procedures, histological subtypes, and surgical approaches.

Association of BRCA1/2 mutations with prognosis and surgical cytoreduction outcomes in ovarian cancer patients: An updated meta‐analysis

AbstractAimThis meta‐analysis was conducted to evaluate the impact of BRCA mutations on survival outcomes of ovarian cancer patients and assess whether the BRCA status was an independent predictor of complete cytoreduction.MethodsWe searched the PubMed, Cochrane, EMBASE, Scopus, Web of Science, and Google Scholar databases for studies that evaluated the associations among BRCA mutations, ovarian cancer survival and surgical cytoreduction before August 2021 based on specific inclusion and exclusion criteria.ResultsWe identified 61 articles that compared the clinical features, survival outcomes, and optimal surgical cytoreduction rates between BRCA‐positive patients and BRCA‐negative patients. The results showed that BRCA mutation carriers were diagnosed with ovarian cancer at a younger age than the age at which nonmutation carriers were diagnosed. In addition, BRCA mutation carriers were more likely to be in the International Federation of Gynecology and Obstetrics (FIGO) stage III‐IV, and the pathological grade was commonly grade 3. The pathological type of BRCA mutation carriers was more likely to be high‐grade serous carcinoma. Patients with BRCA mutations had higher response rates to platinum‐based chemotherapy than the noncarriers. However, patients in both groups had equivalent rates of surgical cytoreduction, and BRCA‐positive patients had longer overall survival (OS) time (HR = 0.65; 95% confidence interval [CI]: 0.59, 0.73; p &lt; 0.001) and longer progression‐free survival (PFS) (HR = 0.72; 95% CI: 0.63, 0.82; p &lt; 0.001).ConclusionBRCA mutations appear to be associated with improved OS and PFS in patients with ovarian cancer. However, we did not find any difference in the surgical resection rate between participants in the two groups.

Contribution of large genomic rearrangements in PALB2 to familial breast cancer: implications for genetic testing

Background PALB2 is the most important contributor to familial breast cancer after BRCA1 and BRCA2. Large genomic rearrangements (LGRs) in BRCA1 and BRCA2 are routinely assessed in clinical testing and are a significant contributor to the yield of actionable findings. In contrast, the contribution of LGRs in PALB2 has not been systematically studied. Methods We performed targeted sequencing and real-time qPCR validation to identify LGRs in PALB2 in 5770 unrelated patients with familial breast cancer and 5741 cancer-free control women from the same Australian population. Results Seven large deletions ranging in size from 0.96 kbp to 18.07 kbp involving PALB2 were identified in seven cases, while no LGRs were identified in any of the controls. Six LGRs were considered pathogenic as they included one or more exons of PALB2 and disrupted the WD40 domain at the C terminal end of the PALB2 protein while one LGR only involved a partial region of intron 10 and was considered a variant of unknown significance. Altogether, pathogenic LGRs identified in this study accounted for 10.3% (6 of 58) of the pathogenic PALB2 variants detected among the 5770 families with familial breast cancer. Conclusions Our data show that a clinically important proportion of PALB2 pathogenic mutations in Australian patients with familial breast cancer are LGRs. Such observations have provided strong support for inclusion of PALB2 LGRs in routine clinical genetic testing.

Distribution of human papillomavirus genotypes in western China and their association with cervical cancer and precancerous lesions

The aim of this study was to describe the distribution of human papillomavirus (HPV) genotypes among cervical cancers and pre-cancers in Shaanxi province of western China. A total of 17,341 women who were screened for cervical cancer from January 2014 to December 2016, using HPV genotyping and ThinPrep cytologic test were included. The prevalence and attribution of HPV genotypes were stratified by cervical lesion and age group. Of the subjects, 26.3% were infected with HPV, 28.0% of whom had multiple infections. The crude HPV prevalence increased from atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions (ASCUS/LSIL, 64.3%) to high-grade squamous intraepithelial lesions (HSIL, 79.8%) and to invasive cervical cancer (ICC, 89.7%, P < 0.001). The three most prevalent genotypes were HPV 16 (8.0%), 58 (4.2%), and 52 (4.0%), and HPV 16, 31 and 33 were positively correlated with increased severity of cervical lesions. Additionally, the divalent vaccine genotypes HPV 16 and 18 accounted for 68.2% of ICC cases. Although 78.5% of ICC and 60.3% of HSIL cases were attributed to 9-valent vaccine genotypes, the other genotypes not covered by any vaccine still resulted in increases in coverage, with 1.5% for ICC, 5.3% for HSIL, and 13.5% for ASCUS/LSIL. HPV prevalence in western China was consistent with other regions of China. Early vaccination with 9-valent HPV vaccine is recommended in this locality for females younger than 26 years with no prior infection, while divalent the vaccine is more appropriate for women between 26 and 45 years, considering the efficacy, safety and cost-effectiveness of vaccines.