Long Non-coding RNA PVT1 Promotes Cell Proliferation and Migration by Silencing ANGPTL4 Expression in Cholangiocarcinoma.
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ABSTRACT:
SUBMITTER: Yu Y
PROVIDER: S-EPMC6205330 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundLncRNA can regulate gene at various levels such as apparent genetics, alternative splicing, and regulation of mRNA degradation. However, the molecular mechanism of LncRNA in cholangiocarcinoma is still unclear. This deserves further exploration.MethodsWe investigated the expression of AGAP2-AS1 in 32 CCA tissues and two CCA cell lines. We found a LncRNA AGAP2-AS1 which induced by SP1 has not been reported in CCA, and Knockdown and overexpression were used to investigate the biological role of AGAP2-AS1 in vitro. CHIP and RIP were performed to verify the putative targets of AGAP2-AS1.ResultsAGAP2-AS1 was significantly upregulated in CCA tumor tissues. SP1 induced AGAP2-AS1 plays an important role in tumorigenesis. AGAP2-AS1 knockdown significantly inhibited proliferation and caused apoptosis in CCA cells. In addition, we demonstrated that AGAP2-AS1 promotes the proliferation of CCA.ConclusionsWe conclude that the long non-coding RNA AGAP2-AS1 plays a role in promoting the proliferation of cholangiocarcinoma.
| S-EPMC7852216 | biostudies-literature
Project description:Despite progress in diagnostics and treatment for preeclampsia, it remains the foremost cause of maternal and foetal perinatal morbidity and mortality worldwide. Over recent years, various lines of evidence have emphasized long non-coding RNAs (lncRNAs) which function as an innovative regulator of biological behaviour, as exemplified by proliferation, apoptosis and metastasis. However, the role of lncRNAs has not been well described in preeclampsia. Here, we identified a lncRNA, PVT1, whose expression was down-regulated in qRT-PCR analyses in severe preeclampsia. The effects of PVT1 on development were studied after suppression and overexpression of PVT1 in HTR-8/SVneo and JEG3 cells. PVT1 knockdown notably inhibited cell proliferation and stimulated cell cycle accumulation and apoptosis. Exogenous PVT1 significantly increased cell proliferation. Based on analysis of RNAseq data, we found that PVT1 could affect the expression of numerous genes, and then investigated the function and regulatory mechanism of PVT1 in trophoblast cells. Further mechanistic analyses implied that the action of PVT1 is moderately attributable to its repression of ANGPTL4 via association with the epigenetic repressor Ezh2. Altogether, our study suggests that PVT1 could play an essential role in preeclampsia progression and probably acts as a latent therapeutic marker; thus, it might be a useful prognostic marker when evaluating new therapies for patients with preeclampsia.
| S-EPMC5783862 | biostudies-other
Project description:Recently, long noncoding RNAs (lncRNAs) have been shown to play significant regulatory roles in human tumorigenesis. However, the biological function of lncRNAs in cholangiocarcinoma (CCA) remains largely unknown. In this study, DANCR was shown to be significantly upregulated in CCA. DANCR regulated the proliferation and migration of CCA cells in vitro. Moreover, downregulation of DANCR suppressed CCA cells proliferation in vivo. RNA-seq revealed that DANCR knockdown preferentially affected genes linked with cell proliferation and cell differentiation. Furthermore, mechanistic investigation validated that DANCR could bind EZH2 and modulate the histone methylation of promoter of FBP1, thereby regulating CCA cells growth and migration. Taken together, these results demonstrated the significant roles of DANCR in CCA and may provide a theoretical basis for clinical diagnosis and treatment of CCA.
| S-EPMC6683119 | biostudies-literature
Project description:Mounting evidence demonstrates that long non-coding RNAs (lncRNAs) are novel transcripts governing multiple biological processes, and their dysregulation is involved in the development and progression of multiple types of cancers. Small Nucleolar RNA Host Gene 20 (SNHG20) is a 2183 bp lncRNA, and its overexpression predicts poor prognosis in colorectal cancer and hepatocellular carcinoma. However, the clinical relevance of SNHG20 and its molecular mechanisms affecting cancer cell phenotype have not been documented. Here, we found that SNHG20 was upregulated in non-small cell lung cancer (NSCLC) tissues compared with normal samples. Higher SNHG20 expression was significantly associated with advanced tumor, lymph node and metastases (TNM) stage and tumor size, as well as poorer overall survival. Moreover, knockdown of SNHG20 repressed NSCLC cell proliferation, migration and induced cell apoptosis. Mechanistic investigations revealed that SNHG20 could interact with EZH2 (enhancer of zeste homolog 2), thereby repressing P21 expression. Furthermore, rescue experiments indicated that SNHG20 functioned as an oncogene partly via repressing p21 in NSCLC cells. Taken together, our findings demonstrate that SNHG20 is a new candidate for use in NSCLC diagnosis, prognosis and therapy.
| S-EPMC5682652 | biostudies-literature
Project description:Hepatocellular carcinoma has been identified as the fifth most common cancer in men and the ninth in women worldwide. Despite many efforts have been made in recent years, the overall survival rate of patients with hepatocellular carcinoma still remain unsatisfied. Therefore, exploring the mechanisms underlying the progression of hepatocellular carcinoma is essential for developing novel treatments to improve patient prognosis. HOXA11-AS, transcribed from the opposite strand of the protein-coding gene HOXA11, has been identified to be associated with the malignant characteristics of several cancers. However, the biological role and molecular mechanism of HOXA11-AS in hepatocellular carcinoma still need to be further investigated. In the current study, the expression of HOXA11-AS in the hepatocellular carcinoma cell lines and tissues was measured by quantitative real-time PCR. Loss-of-function and gain-of-function approaches were applied to investigate the proliferative function of HOXA11-AS in hepatocellular carcinoma cells. Results from flow cytometric analysis of apoptosis and cell cycle distribution revealed that HOXA11-AS promoted hepatocellular carcinoma cells proliferation through regulating cell cycle and apoptosis. Gene chip technology and quantitative real-time PCR confirmed that DUSP5 was a downstream target of HOXA11-AS. RNA immune co-precipitation assays, RNA pull-down and Chromatin immunoprecipitation assays confirmed that HOXA11-AS could recruit EZH2 to the promoter region of DUSP5, which therefore suppressed the transcription of DUSP5. Collectively, these findings revealed that HOXA11-AS functions as an oncogene in hepatocellular carcinoma through interacting with polycomb-repressive complex2.
| S-EPMC5752538 | biostudies-literature
Project description:BackgroundAcquired drug-resistance is the major risk factor for poor prognosis and short-term survival in patients with osteosarcoma (OS). Accumulating evidence has revealed that long noncoding RNAs (lncRNAs), including plasmacytoma variant translocation 1 (PVT1), play potential regulatory roles in the malignant development of OS. Considering the subcellular distribution of PVT1 as both nuclear and cytoplasmic lncRNA, a thorough exploration of its extensive mechanisms becomes essential.MethodsThe GEO database was utilized for the acquisition of gene expression data, which was subsequently analyzed to fulfill the research objectives. The subcellular localization of PVT1 in OS cells was determined using fluorescence in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the sensitivity of OS cells to doxorubicin was comprehensively evaluated through measurements of cell viability, site-specific proliferation capacity, and the relative expression abundance of multidrug resistance-related proteins (MRPs). In order to investigate the differential response of OS cells with varying levels of PVT1 expression to doxorubicin, pulmonary metastasis mice models were established for in vivo studies. Molecular interactions were further examined using the dual-luciferase assay and RNA immunoprecipitation assay (RIP) to analyze the binding sites of miR-15a-5p and miR-15b-5p on PVT1 and G1/S-specific cyclinD1 (CCND1) mRNA. Furthermore, the chromatin immunoprecipitation (ChIP) and dual-luciferase assay were employed to assess the transcriptional activation of the proto-oncogene c-myc (MYC) on the CCND1 promoter and identify the corresponding binding sites.ResultsIn doxorubicin resistant OS cells, transcription levels of PVT1, MYC and CCND1 were significantly higher than those in original cells. In vivo experiments demonstrated that OS cells rich in PVT1 expression exhibited enhanced tumorigenicity and resistance to doxorubicin. In vitro experiments, it has been observed that overexpression of PVT1 in OS cells is accompanied by an upregulation of CCND1, thereby facilitating resistance to doxorubicin. Nonetheless, this PVT1-induced resistance can be effectively attenuated by the knockdown of CCND1. Mechanistically, PVT1 functions as a competitive endogenous RNA (ceRNA) that influences the expression of CCND1 by inhibiting the degradation function of miR-15a-5p and miR-15b-5p on CCND1 mRNA. Additionally, as a neighboring gene of MYC, PVT1 plays a role in maintaining MYC protein stability, which further enhances MYC-dependent CCND1 transcriptional activity.ConclusionThe resistance of OS cells to doxorubicin is facilitated by PVT1, which enhances the expression of CCND1 through a dual mechanism. This findings offer a novel perspective for comprehending the intricate regulatory mechanisms of long non-coding RNA in influencing the expression of coding genes.
| S-EPMC10665705 | biostudies-literature
Project description:Long non-coding RNA urothelial carcinoma-associated 1 (UCA1) has a role in various common types of human malignancy, including cholangiocarcinoma; however, the expression and function of UCA1 in intrahepatic cholangiocarcinoma (ICC) has remained elusive. In the present study, it was observed that UCA1 expression was significantly upregulated in ICC tissues and cell lines compared with that in the adjacent non-tumour tissues and a human intrahepatic biliary epithelial cell line, respectively. The increased expression of UCA1 was significantly associated with lymph node metastasis and clinical T-stage in ICC. Furthermore, the ICC patients with high expression of UCA1 had a shorter survival time when compared with that of patients with low UCA1 expression. Knockdown of UCA1 caused a significant decrease in ICC cell proliferation and invasion, while ectopic overexpression of UCA1 significantly promoted the proliferation and invasion of ICC cells. Furthermore, it was revealed that UCA1 directly binds to microRNA (miR)-122 to negatively regulate its expression in ICC cells. In addition, miR-122 mimics abrogated the promoting effects of UCA1 on ICC cell proliferation and invasion. In addition, an inverse correlation between miR-122 and UCA1 expression in ICC tissues was observed. In conclusion, the present study demonstrates that the lncRNA UCA1 promotes ICC cell proliferation and invasion at least in part by targeting miR-122, suggesting that the UCA1/miR-122 interaction may become a potential therapeutic target for the treatment of ICC.
| S-EPMC6566031 | biostudies-literature
Project description:Whole genome and transcriptome sequencing technologies have led to the identification of many long non-coding RNAs (lncRNAs) and stimulated the research of their role in health and disease. LncRNAs participate in the regulation of critical signaling pathways including cell growth, motility, apoptosis, and differentiation; and their expression has been found dysregulated in human tumors. Thus, lncRNAs have emerged as new players in the initiation, maintenance and progression of tumorigenesis. PVT1 (plasmacytoma variant translocation 1) lncRNA is located on chromosomal 8q24.21, a large locus frequently amplified in human cancers and predictive of increased cancer risk in genome-wide association studies (GWAS). Combined, colorectal and gastric adenocarcinomas are the most frequent tumor malignancies and also the leading cause of cancer-related deaths worldwide. PVT1 expression is elevated in gastrointestinal tumors and correlates with poor patient prognosis. In this review, we discuss the mechanisms of action underlying PVT1 oncogenic role in colorectal and gastric cancer such as MYC upregulation, miRNA production, competitive endogenous RNA (ceRNA) function, protein stabilization, and epigenetic regulation. We also illustrate the potential role of PVT1 as prognostic biomarker and its relationship with resistance to current chemotherapeutic treatments.
| S-EPMC7005105 | biostudies-literature
Project description:Liver cancer (LC) is one of the primary contributors of cancer-associated death worldwide. Long non-coding RNAs (lncRNAs) have been shown to participate in almost every aspect of cell biology and serve fundamental roles in carcinogenesis and cancer progression, including in LC. However, the clinical significance and functional role of the lncRNA breast cancer anti-estrogen resistance 4 (BCAR4) in LC have not yet been identified. The present study measured the expression levels of BCAR4 in LC cells and tissues, and discovered that BCAR4 was upregulated in LC tissues compared with adjacent normal tissues. Furthermore, high BCAR4 expression was associated with the presence of multiple tumors and advanced Tumor-Node-Metastasis stages (III/IV). Survival analysis found that high BCAR4 expression indicated poor overall survival (OS) and progression-free survival (PFS). By analyzing the risk factors of poor OS and PFS using univariate analysis and multivariate analysis, high BCAR4 expression was revealed to be an independent risk factor of poor prognosis. In addition, the role of BCAR4 was further investigated in vitro, which revealed overexpression of BCAR4 to markedly promote the proliferation, migration and invasion of LC cells. Conversely, the loss of BCAR4 expression repressed the proliferation, migration and invasion of LC cells. In conclusion, BCAR4 is overexpressed in LC and is associated with LC progression. Therefore, BCAR4 may be used as a potential prognostic marker in LC.
| S-EPMC7400972 | biostudies-literature
Project description:Cholangiocarcinoma is a devastating liver cancer characterized by high aggressiveness and therapy resistance, resulting in poor prognosis. Long non-coding RNAs and signals imposed by oncogenic pathways, such as transforming growth factor β (TGFβ), frequently contribute to cholangiocarcinogenesis. Here, we explore novel effectors of TGFβ signaling in cholangiocarcinoma. LINC00313 is identified as a novel TGFβ target gene. Gene expression and genome-wide chromatin accessibility profiling reveal that nuclear LINC00313 transcriptionally regulates genes involved in Wnt signaling, such as the transcriptional activator TCF7. LINC00313 gain-of-function enhances TCF/LEF-dependent transcription, promotes colony formation in vitro and accelerates tumour growth in vivo. Genes affected by LINC00313 over-expression in CCA tumours are associated with KRAS and TP53 mutations and reduce overall patient survival. Mechanistically, ACTL6A and BRG1, subunits of the SWI/SNF chromatin remodelling complex, interact with LINC00313 and affect TCF7 and SULF2 transcription. We propose a model whereby TGFβ induces LINC00313 in order to regulate expression of hallmark Wnt pathway genes, in co-operation with SWI/SNF. By modulating key genes of the Wnt pathway, LINC00313 fine-tunes Wnt/TCF/LEF-dependent transcriptional responses and promotes cholangiocarcinogenesis.
| S-SCDT-10_1038-S44319-024-00075-Z | biostudies-other