RESUMO
Cervical cancer (CC), as a common female malignant tumor in the world, is an important risk factor endangering women's health worldwide. The purpose of this study was to investigate the role of RBM15 in CC. The TCGA database was used to screen differentially expressed m6A genes in normal and tumor tissues. QRT-PCR was used to quantify HEIH, miR-802, EGFR, cell stemness, and epithelial-mesenchymal transition (EMT)-related genes. The interaction between HEIH and miR-802 was verified by dual-luciferase reporter assay and RIP assay. The occurrence of tumor cells after different treatments was detected by CCK-8, transwell and EdU staining. BALB/c nude mice were used to examine the effects of different treatments on tumor growth and cell stemness in vivo. RBM15 was upregulated in tumor tissues and cells. M6A was highly enriched in HEIH and enhances its RNA stability. HEIH acts as an oncogenic lncRNA to promote CC cell proliferation, migration and tumor growth. Mechanistically, HEIH regulates tumor cell stemness and promotes the proliferation and migration of CC cells by competitively adsorbing miR-802 and up-regulating the expression of EGFR. In short, our data shown that the m6A methyltransferase RBM15 could affect tumor cell proliferation, metastasis and cell stemness by stabilizing HEIH expression.
Assuntos
Adenina/análogos & derivados , MicroRNAs , RNA Longo não Codificante , Neoplasias do Colo do Útero , Animais , Camundongos , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/patologia , Camundongos Nus , Receptores ErbB/genética , Receptores ErbB/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
Cuproptosis can serve as potential prognostic predictors in patients with cancer. However, the role of this relationship in ovarian serous cystadenocarcinoma (OV) remains unclear. 376 OV tumor samples were obtained from the Cancer Genome Atlas (TCGA) database, and long non-coding RNAs (lncRNAs) related to cuproptosis were obtained through correlation analysis. The risk assessment model was further constructed by univariate Cox regression analysis and LASSO Cox regression. Bioinformatics was used to analyze the regulatory effect of relevant risk assessment models on tumor mutational burden (TMB) and immune microenvironment. We obtained 5 lncRNAs (AC025287.2, AC092718.4, AC112721.2, LINC00996, and LINC01639) and incorporated them into the Cox proportional hazards model. Kaplan-Meier (KM) curve analysis of the prognosis found that the high-risk group was associated with a poorer prognosis. The receiver operating characteristic (ROC) curve showed stronger predictive power compared to other clinicopathological features. Immune infiltration analysis showed that high-risk scores were inversely correlated with CD8+ T cells, CD4+ T cells, macrophages, NK cells, and B cells. Functional enrichment analysis found that they may act via the extracellular matrix (ECM)-interacting proteins and other pathways. We successfully constructed a reliable cuproptosis-related lncRNA model for the prognosis of OV.
Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , RNA Longo não Codificante , Feminino , Humanos , RNA Longo não Codificante/genética , Cistadenocarcinoma Seroso/genética , Prognóstico , Carcinoma Epitelial do Ovário , Imunoterapia , Neoplasias Ovarianas/genética , Microambiente TumoralRESUMO
The aim of current study was to explore the mechanism of microRNA 142-5p (miR-142-5p) in cervical cancer through mediating the phosphoinositol-3-kinase adaptor protein 1 (PIK3AP1)/PI3K/AKT axis. To this end, reverse transcription-quantitative PCR (RT-qPCR) and Western blot analysis results revealed that miR-142-5p was poorly expressed, whereas PIK3AP1 was highly expressed, in cervical cancer tissues and cells. Furthermore, miR-142-5p was hypermethylated in cervical cancer, as reflected by methylation-specific PCR (MS-PCR) and chromatin immunoprecipitation (ChIP) assessment of enrichment of DNMT1/DNMT3a/DNMT3b in the promoter region of miR-142-5p. A target binding relationship between miR-142-5p and PIK3AP1 was established, showing that miR-142-5p targeted and inhibited the expression of PIK3AP1. Loss- and gain-of-function assays were conducted to determine the roles of miR-142-5p and PIK3AP1 in cervical cancer cells. CCK-8, flow cytometry, and Transwell assay results revealed that overexpression of miR-142-5p in cervical cancer cells downregulated PIK3AP1 and inhibited the PI3K/AKT signaling pathway, leading to reduced proliferation, migration, and invasion capacity of cervical cancer cells but enhanced apoptosis. Collectively, epigenetic regulation of miR-142-5p targeted PIK3AP1 to inactivate the PI3K/AKT signaling pathway, thus suppressing development of cervical cancer, which presents new targets for the treatment of cervical cancer.