Gene therapy is emerging as a valid method for the treatment of ovarian cancer, including small interfering RNA (siRNA). Although it is so powerful, few targeting efficient gene delivery systems seriously hindered the development of gene therapy. In this study, we synthesized a novel gene vector PEG-GO-PEI-FA by functionalized graphene oxide (GO), in which folic acid (FA) can specifically bind to the folate receptor (FR), which is overexpressed in ovarian cancer. Characterizations of the nanocomplexes were evaluated by dynamic light scattering (DLS), atomic force microscopy (AFM), and Fourier transform infrared spectroscopy (FTIR). The siRNA condensation ability and stability were assessed by agarose gel electrophoresis. Cellular uptake efficiency and lysosomal escape ability in ovarian cancer cells were investigated by confocal laser scanning microscopy. Furthermore, cellular biosafety of the system and inhibitory of the siRNA tolerability were evaluated by CCK-8 assay. The size of the PEG-GO-PEI-FA nanocomplexes was 216.1 ± 2.457 nm, exhibiting mild cytotoxicity in ovarian cancer cells. With high uptake efficiency, PEG-GO-PEI-FA can escape from the lysosome rapidly and release the gene. Moreover, PEG-GO-PEI-FA/siRNA can effectively inhibit the growth of ovarian cancer cells. By and large, the PEG-GO-PEI-FA/siRNA may offer a promising strategy for siRNA delivery in the treatment of FR-positive ovarian carcinoma or similar tumors.

Endometriosis (EM) is one of the most common diseases among women of reproductive age. The etiology and pathogenesis of EM remain unclear and therefore there is a lack of effective treatment measures, which affects physical and mental health, as well as the quality of life of patients with EM. Angiogenesis has become a hotspot for research on the pathogenesis of EM; the role of angiogenesis‑related serological markers and anti‑angiogenic therapy in the diagnosis and treatment of EM is promising for early diagnosis and treatment of EM. Angiogenesis in EM is subject to complex regulation by hormones, immunity and associated cytokines. Therefore, novel targets for angiogenesis therapy are also being discovered and developed. The present review summarized the pathological mechanisms of angiogenesis and the value of relevant markers in pathogenesis and diagnosis of EM, along with the status of research on anti‑angiogenic drugs in the treatment of EM. The role of angiogenesis in EM provides an important reference for treatment and diagnosis, but there is no uniform non‑invasive diagnostic marker and proven strategy for anti‑angiogenesis.

MicroRNAs (miRNAs) dysregulation contributes to tumorigenesis, and it is reported that abnormal miR-92a-3p expression participates in multiple cancers’ occurrence and progression. This study focuses on miR-92a-3p’s functions and regulatory mechanism in breast cancer (BC). The current study proved miR-92a-3p expression was enhanced in BC tissues and cells, and its high expression was related to increased TNM stage and larger tumor size of BC patients. Functionally, transfection of miR-92a-3p mimics facilitated BC cell proliferation and metastasis, yet transfection of miR-92a-3p inhibitors functioned oppositely. In addition, BTG2 was verified as a direct miR-92a-3p target in BC cells. This research indicated that miR-92a-3p facilitates BC cell proliferation and metastasis through repressing BTG2 expression. GRAPHICAL ABSTRACT

Ovarian carcinoma is one of the most common gynecological cancers with high mortality rates. Numerous evidences demonstrate that cancer cells undergo metabolic abnormality during tumorigenesis in tumor microenvironment and further facilitate tumor progression. Succinate dehydrogenase (SDH or Complex II) is one of the important enzymes in the tricarboxylic acid (TCA) cycle. Succinate dehydrogenase subunit B (SDHB) gene, which encodes one of the four subunits of SDH, has been recognized as a tumor suppressor. However the role of SDHB in ovarian cancer is still unclear. Using the SDHB specific siRNA and overexpression plasmid, the expression of SDHB was silenced and conversely induced in ovarian cancer cell lines SKOV3 and A2780, respectively. The possible role of SDHB in ovarian cancer was investigated in vitro, using proliferation, migration and invasion assays. To explore the mechanism, proliferation and migration related proteins such as Bcl-2, cleaved caspase 3, p-ERK, MMP-2, and p-FAK were examined by western blot. P-P38, p-AMPKα, and HIF-1α were also examined by western blot. CoCl2 was used to induce HIF-1α expression in SKOV3 and A2780 cells. SDHB silencing promoted cell proliferation, invasion, and migration, but inhibited apoptosis of SKOV3 and A2780 cells. In contrast, overexpression of SDHB inhibited cell proliferation, invasion, migration, and promoted apoptosis in SKOV3 cells. It was observed that up-regulation of Bcl-2 and MMP-2, activation of p-P38, p-ERK, and p-FAK, inhibition of cleaved caspase 3 in SDHB-silenced cells. Meanwhile, decreased Bcl-2 and MMP-2, inhibition of p-P38, p-ERK, and p-FAK, activation of cleaved caspase 3 were shown in SDHB-overexpressed SKOV3 cells. HIF-1α, an essential factor in tumor progression, was up-regulated in SDHB-silenced cells with the activation of p-AMPKα and down-regulated in SDHB-overexpressed cancer cells with the decreased p-AMPKα. And SDHB was proved to be decreased due to upregulation of HIF-1α expression in CoCl2-treated cancer cells. Our results firstly revealed that SDHB played a key role in cell proliferation, invasion, migration, and apoptosis of human ovarian carcinoma via AMPK-HIF-1α pathway. SDHB-overexpression might be a new approach to inhibit tumor progression in human ovarian carcinoma.

Prostate cancer (PCa) remains a common cancer with high mortality in men due to its heterogeneity and the emergence of drug resistance. A critical factor contributing to its lethality is the presence of prostate cancer stem cells (PCSCs), which can self-renew, long-term propagate tumors, and mediate treatment resistance. MicroRNA-34a (miR-34a) has shown promise as an anti-PCSC therapeutic by targeting critical molecules involved in cancer stem cell (CSC) survival and functions. Despite extensive efforts, the development of miR-34a therapeutics still faces challenges, including non-specific delivery and delivery-associated toxicity. One emerging delivery approach is ligand-mediated conjugation, aiming to achieve specific delivery of miR-34a to cancer cells, thereby enhancing efficacy while minimizing toxicity. Folate-conjugated miR-34a (folate–miR-34a) has demonstrated promising anti-tumor efficacy in breast and lung cancers by targeting folate receptor α (FOLR1). Here, we first show that miR-34a, a TP53 transcriptional target, is reduced in PCa that harbors TP53 loss or mutations and that miR-34a mimic, when transfected into PCa cells, downregulated multiple miR-34a targets and inhibited cell growth. When exploring the therapeutic potential of folate–miR-34a, we found that folate–miR-34a exhibited impressive inhibitory effects on breast, ovarian, and cervical cancer cells but showed minimal effects on and targeted delivery to PCa cells due to a lack of appreciable expression of FOLR1 in PCa cells. Folate–miR-34a also did not display any apparent effect on PCa cells expressing prostate-specific membrane antigen (PMSA) despite the reported folate’s binding capability to PSMA. These results highlight challenges in the specific delivery of folate–miR-34a to PCa due to a lack of target (receptor) expression. Our study offers novel insights into the challenges and promises within the field and casts light on the development of ligand-conjugated miR-34a therapeutics for PCa.

Introduction: Three different shapes of gold nanoparticles were synthesized in this experiment. At the same time, studies compared their effects with human serum albumin (HSA).Methods: Gold nanoparticles (AuNPs) with three different morphologies, such as, nanospheres (AuNSs), nanorods (AuNRs), and nanoflowers (AuNFs) were synthesized via a seeding method and their characteristic absorption peaks were detected using ultraviolet-visible (UV-vis) absorption spectroscopy, Telectron microscopy (TEM), Dynamic Light Scattering (DLS) and Zeta potential measurements, circular dichroism (CD), and Fourier transform infrared spectroscopy (FTIR) to study the interactions between them and HSA. By comparing the thermodynamic parameters and quenching mechanism of the three materials, similarities and differences were determined in their interactions with HSA.Results: The results showed that with an increase in the concentration of the AuNPs with the three different morphologies, the UV-vis absorption peak intensity of the mixed solution increased, but its fluorescence intensity was quenched. This indicates that the three types of AuNPs interact with HSA, and that the interactions between them represent a static quenching process, which is consistent with the conclusions derived from three-dimensional fluorescence experiments. Through variable-temperature fluorescence experiments, the binding constants, number of binding sites, and thermodynamic parameters of the interactions between the three types of AuNPs and HSA were determined. The Gibbs free energy changes were <0, indicating that the reactions of the three types of AuNPs with HSA are spontaneous, resulting in associated matter. Binding constant measurements indicated that the strongest binding took place between the AuNFs and HSA. In addition, the results of fluorescence, CD spectroscopy, and FTIR showed that three different shapes of AuNPs can induce conformational changes in HSA and reduce the α-helix content. Among them, AuNFs have the smallest ability to induce conformational changes.Discussion: According to studies, AuNFs interact more favorably with HSA. This can be used as a reference for the administration of drugs containing AuNPs.