RESUMEN
Cervical cancer (CC) remains a major cause of cancer-related mortality among women globally. Long noncoding RNAs (lncRNAs) play crucial regulatory roles in various cancers, including CC. This study investigates the function of a novel lncRNA, USP30 antisense RNA 1 (USP30-AS1), in CC tumorigenesis. We analyzed USP30-AS1 expression using RT-qPCR and conducted in vitro loss-of-function assays, as well as in vivo assays, to evaluate the effects of USP30-AS1 silencing on CC cell growth and migration. Additional mechanistic experiments, including RNA pull-down, RNA immunoprecipitation (RIP), and co-immunoprecipitation (Co-IP) assays, were performed to elucidate the regulatory mechanisms influenced by USP30-AS1. We discovered that USP30-AS1 is overexpressed in CC tissues and cells. Silencing USP30-AS1 significantly reduced cell proliferation, migration, invasion, and tumor growth. Moreover, USP30-AS1 was found to modulate the expression of ubiquitin-specific peptidase 30 (USP30) by sponging microRNA-2467-3p (miR-2467-3p) and recruiting the FUS RNA binding protein (FUS), thereby stabilizing ß-catenin and activating the Wnt/ß-catenin signaling pathway. These findings suggest that USP30-AS1 enhances CC cell growth and migration through the miR-2467-3p/FUS/USP30 axis, highlighting its potential as a biomarker for CC.
Asunto(s)
Proliferación Celular , ARN Largo no Codificante , Neoplasias del Cuello Uterino , Vía de Señalización Wnt , beta Catenina , Animales , Femenino , Humanos , Ratones , beta Catenina/metabolismo , beta Catenina/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Exosomas/metabolismo , Exosomas/genética , Regulación Neoplásica de la Expresión Génica/genética , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Vía de Señalización Wnt/genéticaRESUMEN
Ovarian cancer represents a formidable gynecologic malignancy bearing a dismal prognosis owing to the dearth of reliable early detection approaches and a high recurrence rate. Long non-coding RNAs (lncRNAs) have garnered immense attention as key orchestrators involved in diverse biological processes and take part in cancer initiation and progression. The present study investigated the potential significance of lncRNA USP30-AS1 in ovarian cancer prognosis, as well as its putative association with immune cell infiltration in tumor immune microenvironment (TIME). By analyzing publicly available datasets, we identified six lncRNAs with prognostic prediction ability, including USP30-AS1. The results revealed a significant positive correlation of USP30-AS1 expression with the infiltration of immune cells such as Th1 cells, TFH, CD8 T cells, B cells, antigen-presenting dendritic cells (aDC), and plasmacytoid dendritic cells (pDC) in ovarian cancer specimens. These findings provide compelling evidence of the potential involvement of lncRNA in the regulation of the TME in ovarian carcinoma. The outcomes from this study underscore the potential of USP30-AS1 as a promising prognostic biomarker for ovarian cancer. Additionally, the findings offer significant insights into the plausible role of lncRNAs in modulating immune activities, thus adding to our understanding of the disease biology. Additional investigations are necessary to unravel the molecular mechanisms underpinning these connections and validate the results seen in independent cohorts and experimental models.
Asunto(s)
Neoplasias Ováricas , ARN Largo no Codificante , Femenino , Humanos , Línea Celular Tumoral , Detección Precoz del Cáncer , Regulación Neoplásica de la Expresión Génica , Neoplasias Ováricas/patología , Pronóstico , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Microambiente Tumoral/genéticaRESUMEN
Skin cutaneous melanoma (SKCM) is the most malignant skin tumor for it is enormously easy to develop invasion and metastasis. Autophagy is a process by which cellular material is degraded by lysosomes or vacuoles and recycled. Autophagy-related long non-coding RNAs (lncRNAs) have been thought to correlate with SKCM. This study aims to explore the prognostic significance of autophagy-related lncRNAs and establish a prognostic model of autophagy-related lncRNA pairs in SKCM. Firstly, the RNA-seq data and related clinical information were downloaded from the TCGA database. 446 qualified samples were enrolled. 222 autophagy-related genes were obtained from the HADb database. Pearson correlation analysis was conducted to identify autophagy-related lncRNAs (ARLs). After that, we obtained prognosis-related ARLs and autophagy-related lncRNA pairs (ARLPs). Using Lasso-Cox regression analysis, an autophagy-related lncRNA-pair prognostic signature was established. The accuracy of the signature were confirmed through a series of validations in terms of mutation profiles, immunity infiltration, and cellular pathways. And we used the random forest method to find USP30-AS1 as a key mediating factor in SKCM.
Asunto(s)
Melanoma , ARN Largo no Codificante , Neoplasias Cutáneas , Humanos , Melanoma/diagnóstico , Melanoma/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , ARN Largo no Codificante/genética , Autofagia/genética , Algoritmos , Pronóstico , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: The incidence and mortality of colon cancer is increasing recently. It is necessary to identify effective biomarkers for the progression and prognosis of colon cancer. To assess the potential of lncRNA USP30-AS1 (USP30-AS1) in serving as the biomarker of colon cancer and unearth the underlying mechanism. METHODS: There were 123 colon cancer patients enrolled. The expression of USP30-AS1 was evaluated with PCR in tissue and cell samples. The clinical significance of USP30-AS1 was assessed with a series of statistical methods, while the CCK8 and Transwell assay were conducted to estimate its biological effect on the colon cancer cellular processes. In mechanism, the interaction of USP30-AS1 with miR-765 was evaluated with the dual-luciferase reporter assay. RESULTS: In colon cancer tissues, the USP30-AS1 downregulation and the miR-765 upregulation were observed, and there was a negative correlation between the USP30-AS1 expression level and the miR-765 expression level. The downregulation of USP30-AS1 related to the malignant progression and served as an adverse prognostic indicator of colon cancer. The overexpression of USP30-AS1 dramatically suppressed colon cancer cellular processes, which was alleviated by miR-765. CONCLUSIONS: USP30-AS1 predicts the malignancy and prognosis of colon cancer patients. USP30-AS1 suppressed the progression of colon cancer through modulating miR-765.
Asunto(s)
Neoplasias del Colon , MicroARNs , ARN Largo no Codificante , Línea Celular Tumoral , Proliferación Celular , Neoplasias del Colon/genética , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismoRESUMEN
Acute myeloid leukemia (AML) is a malignant tumor derived from leukemia stem cells, with complicated pathogenesis. LncRNAs play an important role in tumors genesis and progression. According to results from bioinformatics analysis, lncRNA USP30-AS1 is highly expressed in AML and both the high expression of USP30-AS1 and low methylation level at Cg03124318 locus of USP30-AS1 gene promoter are associated with poor prognosis of AML. This study knocked down and overexpressed USP30-AS1 to determine the roles in AML cell lines. High-throughput sequencing was performed to explore the genes regulated by USP30-AS1. Results showed that USP30-AS1 promoted AML cell viability and inhibited apoptosis. Genes regulated by USP30-AS1 are mainly related to genetic regulation and immune system. Among them, USP30 and ANKRD13A genes are close to USP30-AS1 gene in chromosome. Knockdown of USP30, but not ANKRD13A, abolished the cancer-promoting effects of USP30-AS1. ANKRD13A recognizes Lys-63-linked polyubiquitin chain in HLA-I. USP30-AS1 induced HLA-I internalization from the cell membrane by up-regulating ANKRD13A, which might induce the immune escape of AML cells. ChIP analysis revealed that the regulatory effects of USP30-AS1 on USP30 and ANKRD13A are associated with H3K4me3 and H3K27Ac. In summary, USP30-AS1 probably promotes AML cell survival by cis-regulating USP30 and ANKRD13A.
Asunto(s)
Supervivencia Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/fisiología , Tioléster Hidrolasas/genética , Tioléster Hidrolasas/metabolismo , Carcinogénesis/genética , Línea Celular Tumoral , Humanos , PronósticoRESUMEN
Glioblastoma is the most serious type of brain cancer with poor prognosis. Here, using the publicly available glioma database, we identified that USP30-AS1, an antisense lncRNA locating on the opposite strand of USP30 locus, is upregulated in human gliomas, particularly in high grade glioma. High level of USP30-AS1 is correlated with poor survival in both primary and recurrent glioma patients. USP30-AS1 regulates mitochondrial homeostasis and mitophagy in glioblastoma cells. Knockdown of USP30-AS1 decreases mitochondrial protein expression and mitochondrial mass, promotes mitochondrial uncoupler-induced mitophagy. However, USP30-AS1 does not regulate USP30 expression in a cis-regulatory manner. In summary, this study proposed that USP30-AS1 may serve as a valuable prognostic marker for gliomas. USP3-AS1 is a negative regulator of mitophagy and the regulatory effect is USP30-independent. USP30-AS1 mediated repression of mitophagy may contribute to the loss of mitochondrial homeostasis and tumor development in glioma.