GGTLC1 knockdown inhibits the progression of endometrial cancer by regulating the TGF-ß/Smad signaling pathway.

Purpose: Endometrial cancer (EC) poses a serious risk to females worldwide; thus, a deep understanding of EC is urgently required. The role and mechanisms of gamma-glutamyltransferase light chain 1 (GGTLC1) in EC remain obscure. This study aims to elucidate the function and mechanisms underlying GGTLC1's involvement in EC. Methods: Bioinformatic tools and databases were used to analyze GGTLC1 and its associated gene expression in EC tissues. Functional enrichment explorations and immune infiltration analyses were conducted, together with investigation into the methylation status of GGTLC1. Western blotting and Quantitative real-time PCR quantified expression levels. Additional experimental methodologies elucidated the role of GGTLC1 in EC progression. Transcriptome sequencing identified potential regulatory pathways for GGTLC1, and tumor growth was evaluated in vivo using HEC-1A cells in nude mice. Results: GGTLC1 was upregulated and negatively correlated with immune cell infiltration and DNA methylation in EC. Cell migration and proliferation were reduced following GGTLC1 knockdown, together with arrest at the G0/G1 phase and an upsurge in apoptosis. Compared to the knockdown group, TGF-ß/Smad signaling pathway was up-regulated in the negative control group of EC cells by transcriptome analysis. The levels of TGF-ß, pSmad2, and pSmad3 followed the same decreasing trend, whereas Smad3 and Smad2 protein levels remained unchanged. Conclusion: Knockdown of GGTLC1 attenuates EC development through the TGF-ß/Smad pathway, positioning GGTLC1 as a promising target for EC treatment.

Polyetherimide- and folic acid-modified Fe3 O4 nanospheres for enhanced magnetic hyperthermia performance.

Recent studies have highlighted the development prospects of magnetic hyperthermia in cancer therapy. A few studies on the application of Fe3 O4 nanospheres for the magnetic hyperthermia of gynecological malignancies have achieved certain efficacy, but there was no visible progress currently. In this work, Fe3 O4 nanospheres modified with polyetherimide (PEI) and folic acid (FA) were synthesized using a hydrothermal method for possible utility in biocompatible and active tumor-targeting magnetic induction hyperthermia. The PEI- and FA-coated Fe3 O4 nanospheres showed high crystallinity, well-dispersed spherical structures and ideal Ms value. As a result, the designed Fe3 O4 @ PEI@FA nanospheres achieved higher specific absorption rate (SAR) values at 360 kHz and 308 Oe, as well as excellent biocompatibility in Hela, SKOV3, HEC-1-A and NIH3T3 cells. These nanospheres can be used as an optimal heating agent for the magnetic hyperthermia treatment of gynecological cancers.

Overexpression of BMP9 promotes ovarian cancer progression via Notch1 signaling.

Cell proliferation and migration play important parts in ovarian cancer progression. BMP9, as one of the members of the TGF-ß superfamily and BMP family, plays a diverse and significant array of biological roles, including cell differentiation, proliferation, apoptosis, tumorigenesis, and metabolism. However, the role and mechanism of BMP9 in ovarian cancer progression remains uncertain. We found that the expression of BMP9 was increased in human ovarian cancer cell lines, which induced Notch1 intracellular domain (NICD1) accumulation. And we also found the expression abundance of BMP9 is low in ovarian cancer cells. Thus, we generated recombinant adenoviruses overexpressing BMP9 to perform the research. We found that overexpression of BMP9 promoted ovarian cancer cell proliferative viability, cell cycle progression, cell migration in vitro, and accelerated subcutaneous tumor growth in vivo, which was inhibited by dominant-negative mutant Notch1 recombinant adenoviruses. Besides, we also demonstrated that silencing of BMP9 by recombinant adenoviruses inhibited ovarian cancer cell viability and migration in vitro. Additionally, BMP9-induced ovarian cancer cell progression also involved the elevation of HES2, c-Myc, MMP9, and Cyclin D1, as well as repressed expression of p27. Together, these results revealed that BMP9 acts as a promoting factor in ovarian cancer progression, and overexpression of BMP9 promotes ovarian cancer progression and growth via Notch1 signaling. Thereby our research may provide new insight into the pathogenesis of ovarian cancer and BMP9-Notch1 signaling may serve as a novel therapeutic target axis for ovarian cancer treatment.

LncRNA CTBP1-AS2 sponges miR-216a to upregulate PTEN and suppress endometrial cancer cell invasion and migration.

BACKGROUND: Although lncRNA CTBP1-AS2 has been functionally analyzed only in cardiomyocyte hypertrophy and diabetes, analysis of TCGA dataset revealed its downregulation in endometrial carcinoma (EC), indicating its involvement in EC. RESULTS: In this study we found that CTBP1-AS2 was downregulated in EC and correlated with poor survival. MiR-216a might form base pairs with CTBP1-AS2 based on RNA-RNA interaction, which was confirmed by luciferase activity assay. Interestingly, upregulation of PTEN was observed after CTBP1-AS2 overexpression. Transwell assay showed that CTBP1-AS2 and PTEN overexpression led to decreased cancer cell invasion and migration and reduced enhancing effects of miR-216a on cell invasion and migration. It was known that miR-216a targeted PTEN. CONCLUSION: Therefore, CTBP1-AS2 may sponge miR-216a to upregulate PTEN, thereby suppressing endometrial cancer cell invasion and migration.

Downregulation of hTERT contributes to ovarian cancer apoptosis and inhibits proliferation of ovarian cancer cells.

BACKGROUND: Our study aims to study the effects of the exogenous human telomerase reverse transcriptase (hTERT) interfering gene on the ovarian cancer cell line SKOV3 through proliferation and apoptosis. METHODS: Lipofectamine TM2000 was used to transfer the hTERT interfering gene into the SKOV3 cells. After a predetermined amount of time after transfection with the hTERT interfering genes, the expression of the tumor-related genes was detected using real-time quantitative polymerase chain reaction (RT-qPCR), and relative protein level was detected using western blot analysis. Cell morphology was acquired by microscopy. Cell viability was detected by middle-time-spray (MTS), and cell cycle and apoptosis were detected by flow cytometry. RESULTS: Forty-eight hours after transfection, the expression of tumor-related proteins in the experimental group was increased compared with the control group, and the difference was statistically significant (P<0.05). The cell morphology showed a significant difference between the control group and the hTERT shRNA group. Furthermore, 48 and 72 h after transfection with the hTERT interfering gene, the cell viability inhibition rates of the hTERT shRNA group were 0.77±0.02 and 0.88±0.01 respectively. Compared with the control group, the cell viability inhibition rates were 11.97±2.37 (%) and 18.72±1.01 (%), respectively, with statistically significant differences (P=0.009, P=0.004). Flow cytometry detected the apoptosis peak of SKOV3 cells in the experimental group 48 h after transfection with the hTERT interfering gene. Propidium iodide (PI) and Annexin V-FITC revealed that the apoptotic cells accounted for 18.13% of the total number, which was significantly higher than the 3.85% demonstrated by the control group. CONCLUSIONS: The amount and activity of SKOV3 cells in ovarian cancer was decreased after the exogenous introduction of the hTERT interfering gene.