Min Wang’s research while affiliated with Northeastern University and other places

Zinc finger protein 384 (ZNF384) is a highly conserved transcribed gene associated with the development of multiple tumors, however, its role and mechanism in serous ovarian cancer (SOC) are unknown. We first confirmed that ZNF384 was abnormally highly expressed in SOC tissues by bioinformatics analysis and immunohistochemistry. We further used lentivirus packaging and transfection techniques to construct ZNF384 overexpression or knockdown cell lines, and through a series of cell function experiments, gradually verified that ZNF384 promoted a series of malignant behaviors of SOC cell proliferation, migration, and invasion. By establishing a xenotransplantation model in nude mice, it was confirmed that ZNF384 promoted the progress of SOC in vivo. Mechanistically, Overexpression of ZNF384 enhanced the transcriptional activity of Lin-28 homolog B (LIN28B), which promoted the malignant behavior of SOC cells. In addition, LIN28B could regulate the expression of the downstream factor ubiquitin D (UBD) in SOC cells, further promoting the development of SOC. This study shows that ZNF384 aggravates the malignant behavior of SOC cells through the LIN28B/UBD axis, which may be used as a diagnostic biomarker for patients with SOC. Graphical abstract

Autophagy is a conservative catabolic process that typically serves a cell‐protective function. Under stress conditions, when the cellular environment becomes unstable, autophagy is activated as an adaptive response for self‐protection. Autophagy delivers damaged cellular components to lysosomes for degradation and recycling, thereby providing essential nutrients for cell survival. However, this function of promoting cell survival under stress conditions often leads to malignant progression and chemotherapy resistance in cancer. Consequently, autophagy is considered a potential target for cancer therapy. Herein, we aim to review how natural products act as key modulators of autophagy by regulating cellular stress conditions. We revisit various stressors, including starvation, hypoxia, endoplasmic reticulum stress, and oxidative stress, and their regulatory relationship with autophagy, focusing on recent advances in ovarian cancer research. Additionally, we explore how polyphenolic compounds, flavonoids, alkaloids, terpenoids, and other natural products modulate autophagy mediated by stress responses, affecting the malignant biological behavior of cancer. Furthermore, we discuss their roles in ovarian cancer therapy. This review emphasizes the importance of natural products as valuable resources in cancer therapeutics, highlighting the need for further exploration of their potential in regulating autophagy. Moreover, it provides novel insights and potential therapeutic strategies in ovarian cancer by utilizing natural products to modulate autophagy.

Background To investigate the role of lncRNA LINC00665 in modulating ovarian cancer stemness and its influence on treatment resistance and cancer development. Methods We isolated ovarian cancer stem cells (OCSCs) from the COC1 cell line using a combination of chemotherapeutic agents and growth factors, and verified their stemness through western blotting and immunofluorescence for stem cell markers. Employing bioinformatics, we identified lncRNAs associated with ovarian cancer, with a focus on LINC00665 and its interaction with the CNBP mRNA. In situ hybridization, immunohistochemistry, and qPCR were utilized to examine their expression and localization, alongside functional assays to determine the effects of LINC00665 on CNBP. Results LINC00665 employs its Alu elements to interact with the 3’-UTR of CNBP mRNA, targeting it for degradation. This molecular crosstalk enhances stemness by promoting the STAU1-mediated decay of CNBP mRNA, thereby modulating the Wnt and Notch signaling cascades that are pivotal for maintaining CSC characteristics and driving tumor progression. These mechanistic insights were corroborated by a series of in vitro assays and validated in vivo using tumor xenograft models. Furthermore, we established a positive correlation between elevated CNBP levels and increased disease-free survival in patients with ovarian cancer, underscoring the prognostic value of CNBP in this context. Conclusions lncRNA LINC00665 enhances stemness in ovarian cancer by mediating the degradation of CNBP mRNA, thereby identifying LINC00665 as a potential therapeutic target to counteract drug resistance and tumor recurrence associated with CSCs.

Ovarian cancer is the second most common cause of gynecologic cancer death. Chemoresistance and metastasis remain major challenges for current treatment. Previously, HAPSTR1 was shown to be a target gene of a paclitaxel resistance-associated miRNA. However, the biological function and underlying molecular mechanisms of HAPSTR1 in ovarian cancer progression remain unclear. Herein, we aimed to measure HAPSTR1 expression in ovarian cancer specimens and examine its correlations with clinical features and key functional interactions with other genes and proteins. An immunohistochemistry assay showed that HAPSTR1 was overexpressed in ovarian cancer tissues and was significantly associated with the FIGO stage and clinical outcome. HAPSTR1 overexpression promoted proliferation, invasion and migration in cellular and mouse models, whereas inhibition induced the opposite effects. In addition, HAPSTR1 stimulated the EMT pathway and affected the expression of autophagy biomarkers. Mechanistically, we demonstrated that HAPSTR1 is bound to LRPPRC and PSMD14 via immunoprecipitation. HAPSTR1 suppressed LRPPRC ubiquitination and recruited PSMD14 to interact with LRPPRC. Moreover, LRPPRC knockdown reversed HAPSTR1-mediated improvement in cellular proliferation, invasion, and migration. Our study is the first detailed and comprehensive analysis of HAPSTR1 in cancer progression and offers an experimental basis for the clinical treatment of ovarian carcinoma.

Ovarian cancer (OC) is the 5th most common malignancy in women, and the leading cause of death from gynecologic malignancies. Owing to tumor heterogeneity, lack of reliable early diagnostic methods and high incidence of chemotherapy resistance, the 5-year survival rate of patients with advanced OC remains low despite considerable advances in detection and therapeutic approaches. Therefore, identifying novel therapeutic targets to improve the prognosis of patients with OC is crucial. The expression of glutathione peroxidase 3 (GPX3) plays a crucial role in the growth, proliferation and differentiation of various malignant tumors. In OC, GPX3 is the only antioxidant enzyme the high expression of which is negatively correlated with the overall survival of patients. GPX3 may affect lipid metabolism in tumor stem cells by influencing redox homeostasis in the tumor microenvironment. The maintenance of stemness in OC stem cells (OCSCs) is strongly associated with poor prognosis and recurrence in patients. The aim of the present study was to review the role of GPX3 in OC and investigate the potential factors and effects of GPX3 on OCSCs. The findings of the current study offer novel potential targets for drug therapy in OC, enhance the theoretical foundation of OC drug therapy and provide valuable references for clinical treatment.