Qinmei Feng

RPL35A drives ovarian cancer progression by promoting the binding of YY1 to CTCF promoter

AbstractOvarian cancer is one of the most common gynaecological malignancies with poor prognosis and lack of effective treatment. The improvement of the situation of ovarian cancer urgently requires the exploration of its molecular mechanism to develop more effective molecular targeted drugs. In this study, the role of human ribosomal protein l35a (RPL35A) in ovarian cancer was explored in vitro and in vivo. Our data identified that RPL35A expression was abnormally elevated in ovarian cancer. Clinically, high expression of RPL35A predicted short survival and poor TNM staging in patients with ovarian cancer. Functionally, RPL35A knock down inhibited ovarian cancer cell proliferation and migration, enhanced apoptosis, while overexpression had the opposite effect. Mechanically, RPL35A promoted the direct binding of transcription factor YY1 to CTCF in ovarian cancer cells. Consistently, RPL35A regulated ovarian cancer progression depending on CTCF in vitro and in vivo. Furthermore, RPL35A affected the proliferation and apoptosis of ovarian cancer cells through PPAR signalling pathway. In conclusion, RPL35A drove ovarian cancer progression by promoting the binding of YY1 and CTCF promoter, and inhibiting this process may be an effective strategy for targeted therapy of this disease.

SLC5A6 Regulates Lipid Metabolism and Lymph Node Metastasis in Cervical Cancer via FASN

ABSTRACT The solute carrier protein SLC5A6 is associated with multiple malignant tumors, while its role in cervical cancer (CC) remains unexplored. This study aimed to investigate the expression pattern, biological functions, and underlying mechanisms of SLC5A6 in cervical cancer. It was found that the expression of SLC5A6 was significantly upregulated in cervical cancer tissues, and its high expression was associated with poorer overall survival of patients. In vitro functional experiments conducted in HeLa and SiHa cell lines demonstrated that overexpression of SLC5A6 enhanced cell proliferation, colony formation, and migration abilities, while inhibiting cell apoptosis; conversely, knockdown of SLC5A6 suppressed these oncogenic phenotypes. Further in vivo experiments confirmed that knockdown of SLC5A6 could inhibit the growth of xenograft tumors. Through transcriptomic analysis and pathway enrichment analysis, this study identified lipid metabolism as a key downstream pathway of SLC5A6, in which fatty acid synthase (FASN) serves as a crucial effector molecule. Mechanistically, SLC5A6 is responsible for the transmembrane transport of biotin. Reduced expression of SLC5A6 leads to a decrease in the expression of biotin‐dependent acetyl‐CoA carboxylase (ACC), which in turn downregulates its downstream target gene FASN. Importantly, knockdown of FASN could reverse the promotional effect of SLC5A6 overexpression on the growth of cervical cancer cells, indicating that SLC5A6 promotes cervical cancer progression through FASN‐mediated reprogramming of lipid metabolism. In conclusion, this study identified SLC5A6 as a novel oncogenic factor in cervical cancer and reveals its mechanism of regulating lipid metabolism via FASN, suggesting that targeting the SLC5A6‐FASN axis may serve as a potential therapeutic strategy for cervical cancer.

1-MT inhibits the invasion of CBP-resistant ovarian cancer cells via down-regulating IDO expression and re-activating immune cells function

Abstract Background The indoleamine 2, 3-dioxygenase (IDO) inhibitor 1-methyl-tryptophan (1-MT) is currently being used in clinical trials in patients with relapsed or refractory solid tumors by inhibiting tumor immune escape. A greater understanding of IDO activity is required to begin to understand the molecular mechanism by which drugs work. This study was conducted to investigate of the clinical significance of 1-methyl-tryptophan (1-MT) in treating carboplatin-resistant (CBP-resistant) ovarian cancer and its mechanism of action. Methods Using a medium dose, intermittent treatment method, a clinically relevant CBP-resistant human ovarian cancer cell line (SKOV3/CBP) was established. SKOV3/CBP cells were treated with normal serum (control) or 1-MT (0.25 ng/mL) for 4 h (SKOV3/CBP + 1-MT). Cell proliferation, invasion and IDO expression in SKOV3, SKOV3/CBP and SKOV3/CBP + 1-MT cells were determined by MTT assays, Matrigel invasion chambers assays and ELISAs, respectively. The half-maximal inhibitory concentration (IC50) and resistance index (RI) were also calculated. The killing ability of the NK cells and CD8+ T cells co-cultured with SKOV3, SKOV3/CBP and SKOV3/CBP + 1-MT cells were determined by LDH activity assays and the INF-γcounting method. Results The SKOV3/CBP cell line displayed an increased IC50 compared to the SKOV3 cell line (P < 0.05) under CBP treatment. Treatment with 1-MT significantly decreased the IC50 and RI of SKOV3/CBP cells. Furthermore, 1-MT treatment not only reduced the invasion ability, but also suppressed IDO expression in the drug-resistant SKOV3/CBP + 1-MT cell line as compared to the SKOV3/CBP cell line. Furthermore, 1-MT enhanced the killing ability of NK cells and the amount of INF-γsecreted from CD8+ T cells which were co-cultured with the SKOV3/CBP cell line. Conclusion Our data suggested that 1-MT inhibits the invasion of CBP-resistant ovarian cancer cells via down-regulation of IDO expression which leads to re-activation of immune cell function. We provide a conceptual foundation for the clinical development of 1-MT as an anti-tumor immunomodulator for chemotherapy resistant ovarian cancer patients.