Iron is crucial for cell DNA synthesis and repair, but an excess of free iron can lead to oxidative stress and subsequent cell death. Although several studies suggest that cancer cells display characteristics of ‘Iron addiction’, an ongoing debate surrounds the question of whether iron can influence the malignant properties of ovarian cancer. In the current study, we initially found iron levels increase during spheroid formation. Furthermore, iron supplementation can promote cancer cell survival, cancer spheroid growth, and migration; vice versa, iron chelators inhibit this process. Notably, iron reduces the sensitivity of ovarian cancer cells to platinum as well. Mechanistically, iron downregulates DNA homologous recombination (HR) inhibitor polymerase theta (POLQ) and relieves its antagonism against the HR repair enzyme RAD51, thereby promoting DNA damage repair to resist chemotherapy-induced damage. Additionally, iron tightly regulated by ferritin (FTH1/FTL) which is indispensable for iron-triggered DNA repair. Finally, we discovered that iron chelators combined with platinum exhibit a synergistic inhibitory effect on ovarian cancer in vitro and in vivo. Our findings affirm the pro-cancer role of iron in ovarian cancer and reveal that iron advances platinum resistance by promoting DNA damage repair through FTH1/FTL/POLQ/RAD51 pathway. Our findings highlight the significance of iron depletion therapy, revealing a promising avenue for advancing ovarian cancer treatment.

Purpose: Malignant melanoma is a tumor generated from the basal melanocytes of human epidermis. Primary malignant melanoma of the cervix (PMMC) is derived from cervical melanocytes. It is an uncommon disease, mostly occurring in perimenopausal women. PMMC has a bad prognosis and lacks a defined protocol or treatment standards. The aim of this study was to analyze the impact of different surgical procedures and different adjuvant treatment modalities on their prognosis and to find risk factors for their prognosis by integrating published case report data based on the Chinese population.Methods and Results: This study included 165 patients with PMMC in the Chinese population. We used the Kaplan‐Meier method to build the survival curve, and the log‐rank test to examine the variations among the subgroups. Prognostic factors were examined utilizing the Cox proportional hazards regression model. We found that patients who underwent radical hysterectomy‐based surgery, those who underwent lymphadenectomy, and those who underwent other treatments in addition to surgery had significantly better survival rates. The overall analysis, showed that age, and FIGO Stage II, III, and IV, increased the risk of death. Moreover, radical hysterectomy (RH), total hysterectomy (TAH), lymphadenectomy, and adjuvant therapy were correlated with a decreased mortality risk.Conclusion: After summarizing the current data, we recommend radical hysterectomy, and lymphadenectomy treatment for patients with PMMC. For patients who had already undergone surgery, other treatment options had a positive effect on prognosis. For patients who had already undergone surgery, other treatment options had a positive effect on prognosis; therefore patient‐specific treatment options need to be further discussed.

Recurrent spontaneous abortion (RSA) is a major pregnancy complication with unclear pathogenesis. This study aims to investigate the role of miR-20b-5p and its downstream target HIF-1α in trophoblast function and RSA pathogenesis. Placental villous tissues from uRSA patients and healthy pregnant women were collected to assess trophoblast migration, invasion, apoptosis, and placental angiogenesis. The expression levels of miR-20b-5p and HIF-1α were analyzed using qPCR, Western blot, and immunohistochemistry. HTR-8/SVneo cells were transfected with miR-20b-5p mimics, si-miR-20b-5p, and si-HIF-1α to evaluate their effects on trophoblast function. Luciferase reporter assays were performed to confirm the regulatory relationship between miR-20b-5p and HIF-1α. Trophoblast cells isolated from uRSA patients exhibited impaired trophoblast invasion and increased trophoblast apoptosis, accompanied by increased trophoblast apoptosis. miR-20b-5p was significantly upregulated, whereas HIF-1α expression was downregulated in uRSA placental tissues. Overexpression of miR-20b-5p inhibited trophoblast migration, invasion, and endothelial-like differentiation, while its knockdown enhanced these functions. HIF-1α was identified as a direct target of miR-20b-5p, and its knockdown partially reversed the effects of miR-20b-5p inhibition. miR-20b-5p negatively regulates trophoblast function by targeting HIF-1α, contributing to trophoblast dysfunction and RSA pathogenesis. The miR-20b-5p/HIF-1α axis may serve as a potential therapeutic target for RSA.

Gynecologic cancers (GCs), including ovarian, cervical, and endometrial cancers, represent a substantial global health burden, characterized by high rates of recurrence, therapeutic resistance, and metastatic dissemination. Tumor dormancy—a state in which disseminated tumor cells (DTCs) persist in a non−proliferative, quiescent phase, thereby evading conventional therapies and immune surveillance—constitutes a critical yet often underestimated driver of these clinical challenges. This comprehensive review systematically integrates the multifaceted roles and current research landscape of dormant tumor cells in gynecologic malignancies. The core innovation lies in a three−level analytical framework that examines dormancy through intrinsic molecular switches, extrinsic microenvironmental remodeling, and cross−cancer type comparisons. Specifically, the mechanisms governing dormancy initiation, maintenance, and reactivation are delineated for cervical, ovarian, and endometrial cancers. Several key conclusions emerge from this synthesis. Common regulatory hubs across gynecologic cancers include hypoxic conditions, cell−cycle regulators such as the DREAM complex, stemness−associated pathways exemplified by the HIF−1α/PLD2 axis, and stromal cell interactions, notably cancer−associated fibroblast−extracellular matrix crosstalk. Dormant cells further orchestrate sophisticated immune evasion strategies, including downregulation of major histocompatibility complex class I and upregulation of immune checkpoint molecules, thereby establishing a reservoir of drug−tolerant persister cells that drive post−treatment relapse and acquired resistance. Notably, substantial heterogeneity exists across different gynecologic cancer types: ovarian cancer engages the most diverse repertoire of dormancy−related pathways, while uterine sarcoma remains a conspicuous research gap. Collectively, this review establishes the dormant tumor cell reservoir as a promising therapeutic target to prevent recurrence and overcome therapy resistance. Specific actionable targets—including Dyrk1A, PLD2, LATS1/2, and Egfl6—are proposed, providing a theoretical foundation for the development of novel diagnostic tools and therapeutic strategies aimed at improving long−term outcomes for patients with gynecologic malignancies.