Yan Yang

Tumor Small Extracellular Vesicle‐Transmitted LncRNA CATED Promotes Platinum‐Resistance in High‐Grade Serous Ovarian Cancer

AbstractHigh‐grade serous ovarian cancer (HGSOC) is the most lethal type of gynecological cancer, and platinum‐resistance is a serious challenge in its treatment. Long non‐coding RNAs (lncRNAs) play critical regulatory roles in the occurrence and development of cancers. Here, using RNA sequencing of tumor small extracellular vesicles (sEVs) from HGSOC patients, the lncRNA CATED is identified as significantly upregulated in both tumors and tumor‐derived sEVs in platinum‐resistant HGSOC, and low CATED levels correlate with good prognosis. Functionally, CATED enhances cisplatin resistance by promoting cell proliferation and inhibiting apoptosis in vitro and in vivo. These effects could be transferred via CATED‐overexpressing sEVs from donor cells and HGSOC tumor sEVs. Mechanistically, CATED binds to and upregulates DHX36 via PIAS1‐mediated SUMOylation at the K105 site, and elevated DHX36 levels increase downstream RAP1A protein levels by enhancing RAP1A mRNA translation, consequently activating the MAPK pathway to promote platinum‐resistance in HGSOC. Antisense oligonucleotide mediated knockdown of CATED reverse platinum‐resistance in sEV‐transmitted mouse models via the DHX36‐RAP1A‐MAPK pathway. This study newly identifies a sEV‐transmitted lncRNA CATED in driving HGSOC platinum‐resistance and elucidates the mechanism it regulates the interacting protein through SUMOylation. These findings also provide a novel strategy for improving chemotherapy in HGSOC by targeting CATED.

Pan-cancer analysis of ARNT2 and its oncogenic role in cervical cancer

This study aims to elucidate the role of aryl hydrocarbon receptor nuclear transporter 2 (ARNT2) in cervical cancer (CC) and explore the potential mechanism by which ARNT2 promotes the progression of CC through the protein phosphatase 2A (PP2A)/Akt signaling pathway. Bioinformatics tools were used to analyze the expression level of ARNT2 in cancer and its correlation with cancer prognosis. Western Blot and immunohistochemistry staining were used to detect the expression of ARNT2 protein in CC tissues and cells. ARNT2 was knocked down in SiHa and HeLa cells, respectively. Cell Counting Kit-8 assay and colony formation assay were used to detect changes in cell proliferation. Transwell assay and plate scratch assay were used to detect changes in cell migration and invasion. Western Blot assay was used to detect changes in the expression of PP2A/Akt signaling pathway after ARNT2 expression was downregulated. Finally, a CC xenograft tumor model was constructed to evaluate the effect of ARNT2 on SiHa cell tumorigenesis in vivo. ARNT2 is highly expressed in tumor tissues and cell lines. ARNT2 knockdown can significantly inhibit the proliferation, invasion and migration of SiHa and HeLa cells in vitro and in xenograft models. Further studies have shown that ARNT2 may promote tumor formation by regulating the PP2A/Akt pathway. ARNT2 promotes the malignant biological behavior of CC cells through the PP2A/Akt signaling pathway, confirming its potential as a prognostic marker for CC.