Dataset Information

Long noncoding RNA HOXC-AS3 indicates a poor prognosis and regulates tumorigenesis by binding to YBX1 in breast cancer.

ABSTRACT: Multiple studies have highlighted the importance of long noncoding RNAs in tumorigenesis. However, the molecular mechanisms underlying the role of lncRNAs in breast cancer are not well understood. Recently, the lncRNA HOXC-AS3 has drawn significant attention due to its regulatory effects on the tumorigenesis of human cancers. However, the potential molecular mechanisms whereby it mediates breast cancer progression remain unknown. Based on public breast cancer expression data and using bioinformatics methods, we discovered significantly upregulated expression levels of HOXC-AS3 in diseased tissues. We verified this result in breast cancer samples and found that the expression of HOXC-AS3 was well correlated with the prognosis of breast cancer. In vitro and in vivo experimental evidence suggests that HOXC-AS3 has the potential to regulate tumorigenesis. Further, mechanistic studies demonstrated the potential of HOXC-AS3 in the transcriptional activation of TK1 via its binding to YBX1. Furthermore, the silencing of TK1 reversed HOXC-AS3-mediated increase in breast cancer cell growth and migration. In conclusion, these results indicated the potential value of HOXC-AS as a prognostic biological marker for breast cancer, and possibly, as a therapeutic target.

SUBMITTER: Su J

PROVIDER: S-EPMC7653616 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Long noncoding RNA HOXC-AS3 indicates a poor prognosis and regulates tumorigenesis by binding to YBX1 in breast cancer.

Su Jun J Yu Bo B Zhang Chongguo C Yi Peiqiang P Li Huan H Xu Cheng C Cao Lu L Chen Peizhan P Li Min M Shen Kunwei K Chen Jiayi J

American journal of translational research 20201015 10

Multiple studies have highlighted the importance of long noncoding RNAs in tumorigenesis. However, the molecular mechanisms underlying the role of lncRNAs in breast cancer are not well understood. Recently, the lncRNA HOXC-AS3 has drawn significant attention due to its regulatory effects on the tumorigenesis of human cancers. However, the potential molecular mechanisms whereby it mediates breast cancer progression remain unknown. Based on public breast cancer expression data and using bioinforma ...[more]

PMID: 33194034

Similar Datasets

Project description:BackgroundColorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide, however, the mechanisms of CRC progression remain obscure. The present study investigated the clinical significance and functional role of long noncoding RNA (lncRNA) GIHCG in CRC.MethodsExpression of GIHCG was detected by quantitative real time polymerase chain reaction (qRT-PCR) in seven CRC cell lines and 110 CRC tissues. Comparison of clinicopathological characteristics in the high GIHCG expression group and the low GIHCG expression group was performed. The overall survival (OS) and progression-free survival (PFS) of the patients were depicted with Kaplan-Meier test and compared with Log-rank test. Univariate and multivariate analyses were carried out to detect the risk factors for poor OS and PFS. In addition, expression of GIHCG was silenced with siRNAs in LoVo cells and overexpressed with pcDNA3.1-GIHCG vector in SW480 cells, respectively. And the Transwell assay, Matrigel assay, colony formation assay and Cell Counting Kit-8 assay (CCK-8) were performed to investigate the role of GIHCG in the migration, invasion and proliferation of CRC cells. Besides, the role of GIHCG in chemoresistance was also detected.ResultsGIHCG was overexpressed in seven CRC cell lines and 110 CRC tissues. High GIHCG expression was correlated with lymphovascular invasion, lymph node metastasis, distant metastasis and advanced TNM stages. Moreover, patients with high GIHCG expression had much poorer OS and PFS rates. Besides, high GIHCG expression was identified as an independent risk factor for poor OS and PFS. The Transwell assay and the Matrigel assay discovered that GIHCG deficiency inhibited cell migration and invasion, while ectopic expression of GIHCG promoted migration and invasion. Besides, the colony formation assay and the CCK-8 assay verified that GIHCG increased cell proliferation ability. By establishing 5-fluorouracil (5-FU) and Oxaliplatin (Oxa)-resistant LoVo cells and SW480 cells, we found chemoresistant CRC cells had much higher expression levels of GIHCG. Also, GIHCG facilitated cell survival under 5-FU or Oxa treatment. Furthermore, silencing of GIHCG notably reduced the improved cell survival rates of 5-FU or Oxa-resistant LoVo cells compared with control cells.ConclusionGIHCG contributes to cancer progression and chemoresistance and indicates poor prognosis in CRC. GIHCG may be a promising prognostic biomarker and therapeutic target in CRC.

Project description:BackgroundGastric cancer is the second leading cause of cancer death and remains a major clinical challenge due to poor prognosis and limited treatment options. Long noncoding RNAs (lncRNAs) have emerged recently as major players in tumor biology and may be used for cancer diagnosis, prognosis, and potential therapeutic targets. Although downregulation of lncRNA GAS5 (Growth Arrest-Specific Transcript) in several cancers has been studied, its role in gastric cancer remains unknown. Our studies were designed to investigate the expression, biological role and clinical significance of GAS5 in gastric cancer.MethodsExpression of GAS5 was analyzed in 89 gastric cancer tissues and five gastric cancer cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of GAS5. The effect of GAS5 on proliferation was evaluated by MTT and colony formation assays, and cell apoptosis was evaluated by hochest stainning. Gastric cancer cells transfected with pCDNA3.1 -GAS5 were injected into nude mice to study the effect of GAS5 on tumorigenesis in vivo. Protein levels of GAS5 targets were determined by western blot analysis. Differences between groups were tested for significance using Student's t-test (two-tailed).ResultsWe found that GAS5 expression was markedly downregulated in gastric cancer tissues, and associated with larger tumor size and advanced pathologic stage. Patients with low GAS5 expression level had poorer disease-free survival (DFS; P = 0.001) and overall survival (OS; P < 0.001) than those with high GAS5 expression. Further multivariable Cox regression analysis suggested that decreased GAS5 was an independent prognostic indicator for this disease (P = 0.006, HR = 0.412; 95%CI = 2.218-0.766). Moreover, ectopic expression of GAS5 was demonstrated to decrease gastric cancer cell proliferation and induce apoptosis in vitro and in vivo, while downregulation of endogenous GAS5 could promote cell proliferation. Finally, we found that GAS5 could influence gastric cancer cells proliferation, partly via regulating E2F1 and P21 expression.ConclusionOur study presents that GAS5 is significantly downregulated in gastric cancer tissues and may represent a new marker of poor prognosis and a potential therapeutic target for gastric cancer intervention.

Project description:BackgroundDysregulation of long non-coding RNAs (lncRNAs) is responsible for cancer initiation and development, positioning lncRNAs as not only biomarkers but also promising therapeutic targets for cancer treatment. A growing number of lncRNAs have been reported in hepatocellular carcinoma (HCC), but their functional and mechanistic roles remain unclear.MethodsGene Set Enrichment Analysis was used to investigate the molecular mechanism of UPK1A antisense RNA 1 (UPK1A-AS1). Cell Counting Kit-8 assays, EdU assays, flow cytometry, western blotting, and xenograft assays were used to confirm the role of UPK1A-AS1 in the proliferation of HCC cells in vitro and in vivo. Bioinformatics analyses and quantitative polymerase chain reaction (qRT-PCR) were performed to explore the interplay between UPK1A-AS1 and enhancer of zeste homologue 2 (EZH2). RNA immunoprecipitation (RIP), RNA pull-down assays, western blotting, and qRT-PCR were conducted to confirm the interaction between UPK1A-AS1 and EZH2. The interaction between UPK1A-AS1 and miR-138-5p was examined by luciferase reporter and RIP assays. Finally, the expression level and prognosis value of UPK1A-AS1 in HCC were analyzed using RNA sequencing data from The Cancer Genome Atlas datasets.ResultsWe showed that UPK1A-AS1, a newly identified lncRNA, promoted cellular proliferation and tumor growth by accelerating cell cycle progression. Cell cycle-related genes, including CCND1, CDK2, CDK4, CCNB1, and CCNB2, were significantly upregulated in HCC cells overexpressing UPK1A-AS1. Furthermore, overexpression of UPK1A-AS1 could protect HCC cells from cis-platinum toxicity. Mechanistically, UPK1A-AS1 interacted with EZH2 to mediate its nuclear translocation and reinforce its binding to SUZ12, leading to increased H27K3 trimethylation. Targeting EZH2 with specific small interfering RNA impaired the UPK1A-AS1-mediated upregulation of proliferation and cell cycle progression-related genes. Moreover, miR-138-5p was identified as a direct target of UPK1A-AS1. Additionally, UPK1A-AS1 was significantly upregulated in HCC, and the upregulation of UPK1A-AS1 predicted poor prognosis for patients with HCC.ConclusionsOur study revealed that UPK1A-AS1 promotes HCC development by accelerating cell cycle progression through interaction with EZH2 and sponging of miR-138-5p, suggesting that UPK1A-AS1 possesses substantial potential as a novel biomarker for HCC prognosis and therapy.

Dataset Information

Long noncoding RNA HOXC-AS3 indicates a poor prognosis and regulates tumorigenesis by binding to YBX1 in breast cancer.

Publications

Long noncoding RNA HOXC-AS3 indicates a poor prognosis and regulates tumorigenesis by binding to YBX1 in breast cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets