Systems Biology in Reproductive Medicine

FOXA1 co-activates circODC1 and ODC1 in HPV-positive cervical cancer cell growth

As demonstrated in previous research, hsa_circ_0052602 (circODC1) is dynamically expressed in HPV-positive cervical cancer (CC). CircODC1 expression was quantified using qRT-PCR, and its role in CC cell growth was assessed

LINC00665 affects the malignant biological behavior of ovarian cancer via the miR-148b-3p/KLF5

This study investigated the expression and clinical significance of long intergenic noncoding RNA 00665 (LINC00665) in ovarian cancer (OC), as well as its effect on the malignant biological behavior of OC cells. The expression of LINC00665, miR-148b-3p, and Krüppel-like factor 5 (KLF5) in OC tissues and cells were determined by RT-qPCR. Western blot was used to detect the protein expression of KLF5. The expression patterns of LINC00665 in nuclear and cytoplasm fractions were undertaken using RT-qPCR. In addition, CCK-8 assay, clone formation assay, transwell, scratch test, and flow cytometry were respectively used to detect the cell activity, proliferation, invasiveness, healing of cells, and apoptosis rate of OC cells. Furthermore, the interactions between LINC00665 and miR-148b-3p and between miR-148b-3p and KLF5 were verified by the luciferase reporter assay, and the correlations among these three genes were analyzed. LINC00665 expression was upregulated both in OC cell lines and tissues. Si-LINC00665 inhibited cell proliferation, invasion, and migration and induced apoptosis to a certain extent. The subcellular fraction assay revealed LINC00665 to be located mainly in the cytoplasm. miR-148b-3p was a target of LINC00665, and KLF5 was directly targeted by miR-148b-3p. Si-LINC00665 inhibited KLF5 expression, miR-148b-3p inhibitor promoted KLF5 expression, and si-KLF5 inhibited LINC00665 expression. Interestingly, the expression of LINC00665 was reversely associated with miR-148b-3p expression but positively correlated with KLF5. Furthermore, miR-148b-3p expression was negatively correlated with KLF5. In addition, si-KLF5 inhibited the malignant biological behavior of OC cells, whereas miR-148b-3p inhibitor had the opposite effect. Most importantly, the si-LINC00665 could reverse the promotion effect of the miR-148b-3p inhibitor on the malignant biological behavior of OC cells. LINC00665 can be used as an effective prognostic indicator of OC, which has the potential to be a new therapeutic target.

Prevalence of human papilloma virus and Chlamydia trachomatis in endometrial and cervical carcinoma: a comparative study in North Indian women

Cervical cancer (Cacx) is the second and endometrial cancer (Ec) is the third most common gynecological cancer worldwide. The present study aims to understand the complex and unexplored conditions occurring in cervix and endometrium of the female genital tract caused due to the infection of the

Co-expressed functional module-related genes in ovarian cancer stem cells represent novel prognostic biomarkers in ovarian cancer

Ovarian cancer is the leading cause of death from gynecologic malignancies. Cancer stem cells (CSC) seem to play a crucial role in tumor metastasis, recurrence, and chemoresistance. Therefore, CSCs offer significant potential for developing therapeutic targets and to understand tumor recurrence and chemoresistance mechanisms. In the present study, our aim was the identification of the gene group in ovarian CSCs (O-CSCs) and the potential of the resultant gene group in ovarian cancer prognosis. Two different microarray data sets were analyzed by comparing gene expression levels between O-CSCs and cancer samples. The O-CSC co-expression network was reconstructed and its modules were identified. According to the analysis results, 74 mutual DEGs were identified. The O-CSC-specific co-expression network included 32 nodes and 95 edges (network density: 19%), while the co-expression network in cancer samples was reconstructed with 74 nodes and 1066 edges (network density: 39%). Understanding of the molecular mechanism and signatures of O-CSCs should provide valuable insight into chemotherapy resistance and recurrence of ovarian tumors. A highly connected 12 gene module in O-CSC samples of BAMB1, NFKB12, EZR, TNFAIP3, C1orf86, PMAIP1, GEM, KHDRBS3, FILIP1, FGFR2, TGFBR3 and PEG10, (network density: 67%) was identified. Prognostic performance of these genes was evaluated independently using six ovarian cancer datasets (n = 1933 patient samples) via survival analysis. These co-expressed genes were determined as prognostic targets in ovarian cancer. Through literature search validation, five genes (C1orf86, PMAIP1, FILIP1, NFKB12 and PEG10) suggested as novel molecular targets in ovarian cancer. The presented prognostic biomarkers here provide a resource for the understanding of tumor recurrence and chemoresistance and may facilitate critical research directions and development of new prognostic and therapeutic strategies for ovarian cancer. CSCs: cancer stem cells; O-CSCs: ovarian CSCs; FACS: fluorescence-activated cell sorting; SP: side population; MP: main population; TFs: transcription factors.

Sex chromosome DSD individuals with mosaic 45,X0 and aberrant Y chromosomes in 46,XY cells: distinct gender phenotypes and germ cell tumour risks§

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Identification of candidate genes for endometrial cancer in multi-omics: a Mendelian randomization analysis

Endometrial cancer is the most common malignant tumor of the uterus, but the underlying genetic mechanisms of EC remain unclear. To identify candidate genes and investigate genetic mechanisms for endometrial cancer, we utilized the summary-data-based Mendelian randomization (SMR) method to investigate causal associations between genetic variants, gene expression, DNA methylation, and endometrial cancer. Three main analyses were conducted utilizing cis-expression and methylation quantitative trait loci (eQTLs and mQTLs) as instrumental variables to examine causal relationships with endometrial cancer, and assessing the causal relationship between DNA methylation and gene expression. Data sources included genetic association data from O'Mara et al. eQTL data from the GTEx database, and mQTL data from McRae et al. Analysis involved the HEIDI test to distinguish pleiotropy, SMR analysis with multiple testing correction, and colocalization analysis to assess associations driven by linkage disequilibrium. Functional enrichment analysis was performed by the Metascape tool. Our study showed that three genes, SNX11, LINC00243, and EVI2A, were identified as causally related to endometrial cancer. SNX11 exhibited a positive causal relationship, while LINC00243 and EVI2A showed negative ones. Furthermore, 24 CpG sites were identified as causally related to endometrial cancer, with cg14424631 (CYP19A1) being the most significant. The study revealed common genes implicated in endometrial cancer, gene expression, and methylation sites, with LINC00243 playing a key role. Colocalization analysis confirmed significant causal relationships between LINC00243, SNX11, and endometrial cancer. Enrichment analysis uncovered pathways like interferon gamma signaling enriched in both endometrial cancer GWAS and e/mQTL. These findings shed light on the molecular mechanisms underlying endometrial cancer development. The study identified candidate genes and DNA methylation loci causally associated with endometrial cancer, which are expected to serve as potential targets for treatment.