Dataset Information

OnclncRNA-626 promotes malignancy of gastric cancer via inactivated the p53 pathway through interacting with SRSF1.

ABSTRACT: Gastric cancer (GC) is a serious health problem worldwide. The potential involvement of long noncoding RNAs in GC progression remains largely unexplored. Here, we identified a novel long noncoding RNA referred to as onclncRNA-626 (oncogenic lncRNA RP11-626H12.3), which was highly upregulated in GC tissues. The high expression levels of onclncRNA-626 in GC patients predicted poor prognoses. Functional assays indicated that onclncRNA-626 could promote the proliferation and metastasis of GC cells in vitro and in vivo. In exploring the molecular mechanisms guiding these functions, we found that onclncRNA-626 specifically interacted with serine- and arginine-rich splicing factor 1 (SRSF1) and increased its stability. SRSF1 was upregulated in GC tissues and correlated with onclncRNA-626 expression and patient survival. Furthermore, RNA-seq data revealed that onclncRNA-626 affected multiple signaling pathways, including the p53 signaling pathway. Rescue experiments showed that onclncRNA-626 probably performed its biological function through SRSF1 mediation of the p53 pathway. Together, our findings demonstrate that onclncRNA-626 promotes GC progression by binding SRSF1; further, this lncRNA is a potential prognostic biomarker for GC patients.

SUBMITTER: Wu ZH

PROVIDER: S-EPMC6834483 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

OnclncRNA-626 promotes malignancy of gastric cancer via inactivated the p53 pathway through interacting with SRSF1.

Wu Zhen-Hua ZH Liu Chen-Chen CC Zhou Yu-Qiang YQ Hu Li-Na LN Guo Wei-Jian WJ

American journal of cancer research 20191001 10

Gastric cancer (GC) is a serious health problem worldwide. The potential involvement of long noncoding RNAs in GC progression remains largely unexplored. Here, we identified a novel long noncoding RNA referred to as onclncRNA-626 (oncogenic lncRNA RP11-626H12.3), which was highly upregulated in GC tissues. The high expression levels of onclncRNA-626 in GC patients predicted poor prognoses. Functional assays indicated that onclncRNA-626 could promote the proliferation and metastasis of GC cells < ...[more]

PMID: 31720086

Similar Datasets

Project description:Multiple myeloma (MM) is the second most common hematological malignancy. An overwhelming majority of patients with MM progress to serious osteolytic bone disease. Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) participates in several steps during cancer development and osteoclast differentiation. This study aimed to explore its role in MM. The gene expression profiling cohorts of MM were applied to determine the expression of AIMP1 and its association with MM patient prognosis. Enzyme-linked immunosorbent assay, immunohistochemistry, and Western blotting were used to detect AIMP1 expression. Protein chip analysis, RNA-sequencing, and chromatin immunoprecipitation and next-generation sequencing were employed to screen the interacting proteins and key downstream targets of AIMP1. The impact of AIMP1 on cellular proliferation was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in vitro and a xenograft model in vivo. Bone lesions were evaluated using tartrate-resistant acid phosphatase staining in vitro. A NOD/SCID-TIBIA mouse model was used to evaluate the effect of siAIMP1-loaded exosomes on bone lesion formation in vivo. AIMP1 expression was increased in MM patients and strongly associated with unfavorable outcomes. Increased AIMP1 expression promoted MM cell proliferation in vitro and in vivo via activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Protein chip assays and subsequent experiments revealed that AIMP1 interacted with acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A) to regulate histone H3 acetylation. In addition, AIMP1 increased histone H3 acetylation enrichment function of GRB2-associated and regulator of MAPK protein 2 (GAREM2) to increase the phosphorylation of extracellular-regulated kinase 1/2 (p-ERK1/2). Furthermore, AIMP1 promoted osteoclast differentiation by activating nuclear factor of activated T cells c1 (NFATc1) in vitro. In contrast, exosome-coated small interfering RNA of AIMP1 effectively suppressed MM progression and osteoclast differentiation in vitro and in vivo. Our data demonstrate that AIMP1 is a novel regulator of histone H3 acetylation interacting with ANP32A in MM, which accelerates MM malignancy via activation of the MAPK signaling pathway.

Project description:BackgroundHypoxia has long been considered as a hallmark of solid tumors and is closely associated with tumor progression. Circular RNAs (circRNAs) have been identified as a critical modulator in various cancers. However, the connections between hypoxia and circRNAs are largely unknown.MethodsHere, we investigated the expression profile of circRNAs in breast cancer (BC) MCF-7 cells under hypoxia and normoxia using microarray. We identified a novel hypoxia-responsive circRNA named circWSB1, whose expression pattern, potential diagnostic value and prognostic significance were assessed by qRT-PCR and in situ hybridization. Loss- and gain-of-function investigations in vivo and in vitro were performed to determine the biological functions of circWSB1. Mechanistically, chromatin immunoprecipitation and dual luciferase reporter assays were carried out to analyze the biogenesis of circWSB1. Furthermore, biotin-labeled RNA pull-down, mass spectrometry, RNA immunoprecipitation, fluorescent in situ hybridization, RNA electrophoretic mobility shift, deletion-mapping, co-immunoprecipitation assays and rescue experiments were applied to investigate the interaction between circWSB1 and Ubiquitin-specific peptidase 10 (USP10) as well as the relationship between USP10 and p53.ResultsWe found that the expression of circWSB1 was significantly upregulated in BC tissues and correlated with poor clinical outcomes, which might serve as an independent prognostic factor for BC patients. Ectopic expression of circWSB1 promoted the proliferation of BC cell in vitro and in vivo. Mechanistically, circWSB1 was transcriptionally upregulated by HIF1α in response to hypoxia and could competitively bind to deubiquitinase USP10 to prevent the access of p53 to USP10 in BC cells, leading to degradation of p53 and tumor progression of BC.ConclusionsTaken together, our findings disclose a novel mechanism that hypoxia-inducible circWSB1 could interact with USP10 to attenuate USP10 mediated p53 stabilization and promote the progression of BC, providing an alternative prognostic biomarker and therapeutic target for BC.

Dataset Information

OnclncRNA-626 promotes malignancy of gastric cancer via inactivated the p53 pathway through interacting with SRSF1.

Publications

OnclncRNA-626 promotes malignancy of gastric cancer via inactivated the p53 pathway through interacting with SRSF1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets