Long non-coding RNA HOTAIR regulates cyclin J via inhibition of microRNA-205 expression in bladder cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Sun X
PROVIDER: S-EPMC4632298 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:The long non-coding RNA HOTAIR is the most differentially expressed gene between upper- and lower-body adipose tissue, yet its functional significance in adipogenesis is unclear. We report that HOTAIR expression is transiently induced during early adipogenic differentiation of gluteofemoral adipose progenitors and repressed in mature adipocytes. Upon adipogenic commitment, HOTAIR regulates protein synthesis pathways and cytoskeleton remodeling with a later impact on mature adipocyte lipid storage capacity. Our results support novel and important functions of HOTAIR in the physiological context of adipogenesis.
| S-EPMC9203762 | biostudies-literature
Project description:BackgroundCisplatin-based chemotherapy is the first line of treatment for bladder cancer. However, cisplatin induces muscle wasting associated with NF-κB and cancer cachexia. HOTAIR, an oncogenic long non-coding RNA (lncRNA), promotes cancer progression in different cancers. Crosstalk between HOTAIR and NF-κB is documented. Prothymosin α (ProT) plays important roles in cancer progression and inflammation. However, the potential link between HOTAIR, ProT, and cisplatin-induced cancer cachexia remains unexplored. Here, we investigated the contribution of HOTAIR in cisplatin-induced cancer cachexia and dissected the potential signaling cascade involving the epidermal growth factor receptor (EGFR), ProT, NF-κB, and HOTAIR.Materials and methodsExpression of ProT and HOTAIR transcripts and their correlations in tumor tissues of bladder cancer patients and bladder cancer cell lines were determined by RT-qPCR. Next, levels of phospho-EGFR, EGFR, phospho-NF-κB, and NF-κB were examined by immunoblot analysis in human bladder cancer cells treated with cisplatin. Expression of HOTAIR in cisplatin-treated cells was also assessed by RT-qPCR. Pharmacological inhibitors and overexpression and knockdown approaches were exploited to decipher the signaling pathway. The murine C2C12 myoblasts were used as an in vitro muscle atrophy model. The syngeneic murine MBT-2 bladder tumor was used to investigate the role of mouse Hotair in cisplatin-induced cancer cachexia.ResultsExpression of ProT and HOTAIR was higher in bladder tumors than in normal adjacent tissues. There were positive correlations between ProT and HOTAIR expression in clinical bladder tumors and bladder cancer cell lines. Cisplatin treatment increased EGFR and NF-κB activation and upregulated ProT and HOTAIR expression in bladder cancer cells. ProT overexpression increased, whereas ProT knockdown decreased, HOTAIR expression. Notably, cisplatin-induced HOTAIR upregulation was abrogated by EGFR inhibitors or ProT knockdown. ProT-induced HOTAIR overexpression was diminished by NF-κB inhibitors. HOTAIR overexpression enhanced, whereas its knockdown reduced, cell proliferation, cachexia-associated pro-inflammatory cytokine expression, and muscle atrophy. Cachexia-associated symptoms were ameliorated in mice bearing Hotair-knockdown bladder tumors undergoing cisplatin treatment.ConclusionsWe demonstrate for the first time a critical role for HOTAIR and identify the involvement of the EGFR-ProT-NF-κB-HOTAIR signaling axis in cisplatin-induced cachexia in bladder cancer and likely other cancers. Our findings also provide therapeutic targets for this disease.
| S-EPMC9724340 | biostudies-literature
Project description:Accumulating evidence highlights the role of long non-coding RNAs (lncRNA) in cellular homeostasis, and their dysregulation in disease settings. Most lncRNAs function by interacting with proteins or protein complexes. While several orthogonal methods have been developed to identify these proteins, each method has its inherent strengths and limitations. Here, we combine two RNA-centric methods ChIRP-MS and RNA-BioID to obtain a comprehensive list of proteins that interact with the well-known lncRNA HOTAIR. Overexpression of HOTAIR has been associated with a metastasis-promoting phenotype in various cancers. Although HOTAIR is known to bind with PRC2 and LSD1 protein complexes, an unbiased and comprehensive method to map its interactome has not yet been performed. Both ChIRP-MS and RNA-BioID data sets show an association of HOTAIR with mitoribosomes, suggesting HOTAIR has functions independent of its (post-)transcriptional mode-of-action.
2022-02-15 | PXD029057 | Pride
Project description:Breast cancer (BC) is the most common cancer type among women, and morbidity and mortality rates are still very high. Despite new innovative therapeutic approaches for all BC molecular subtypes, the discovery of new molecular biomarkers involved in tumor progression has been fundamental for the implementation of personalized treatment strategies and improvement of patient management. Many experimental studies indicate that long non-coding RNAs (lncRNAs) are strongly involved in BC initiation, metastatic progression, and drug resistance. In particular, aberrant expression of HOX transcript antisense intergenic RNA (HOTAIR) lncRNA plays an important role in BC contributing to its progression and represents a predictor of BC metastasis. For its proven prognostic value, HOTAIR could represent a potential therapeutic target in BC. In the present review, we summarize the role of HOTAIR in cancer progression and drug resistance, in particular in BC, and we illustrate the main approaches for silencing it.
| S-EPMC7281113 | biostudies-literature
Project description:Long non-coding RNA HOTAIR has been reported to play a key role in regulating various biological processes in various cancers. However, the roles and mechanisms of HOTAIR in acute myeloid leukaemia (AML) are still unclear and need to be investigated. In this study, we induced differentiation of four AML cell lines by all-trans retinoic acid (ATRA) and found HOTAIR was significantly upregulated in the process. Chromatin immunoprecipitation (ChIP) assays indicated that C/EBPβ upregulated HOTAIR during ATRA induced differentiation in HL-60 cells. By gain- and loss-of-function analysis, we then observed that HOTAIR expression was positively correlated with ATRA-induced differentiation and negatively regulated G1 phase arrest in HL-60 cells. In addition, we found that HOTAIR promoted ATRA-induced differentiation via the regulation of the cell cycle regulator p21 via miR-17-5p. Moreover, we detected the expression of HOTAIR in 84 de novo AML patients, HOTAIR was found significantly downregulated in the AML patients compared to the iron deficiency anaemia (IDA) control group, negatively correlated with the platelet level in M2 patients. In all, our data suggest that HOTAIR may be subtype-specific in AML-M2 patients, also HOTAIR regulates AML differentiation by C/EBPBβ/HOTAIR/miR-17-5p/p21 pathway. The findings of the present study provide a novel insight into the mechanism of lncRNA-mediated differentiation and indicate that HOTAIR may be a promising therapeutic target for leukaemia, especially for AML with M2 type.Abbreviation: AML: acute myeloid leukaemia; APL: acute promyelocytic leukaemia; ATRA: all-trans retinoic acid; CCK8: cell Counting Kit-8; CDKs: cyclin-dependent kinases ; CeRNA: competing endogenous RNAs; ChIP: chromatin immunoprecipitation; CHX: cycloheximide; FAB: French-American-British; FCM: flow cytometry; HOTAIR: HOX transcript antisense RNA; IDA: iron-deficiency anemia; lncRNA: long non-coding RNA; 3'UTR: 3'untranslated region; MT: Mutation type; WT: Wild type; qRT-PCR: Quantitative real-time PCR.
| S-EPMC8489933 | biostudies-literature
Project description:Colorectal cancer (CRC) is a global healthcare problem. Radioresistance is a huge setback for CRC radiotherapy. In this text, the roles and molecular mechanisms of long non-coding RNA HOTAIR in CRC tumorigenesis and radioresistance were further investigated. ATG12 mRNA, HOTAIR, and microRNA-93 (miR-93) levels were measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay. Protein levels of LC3 I, LC3 II, p62, ATG12, cleaved caspase 3, Bax, and Bcl-2 were detected by western blotting assay in cells and were examined by immunohistochemistry (IHC) assay in tissues. Cell survival fractions, viability, and apoptotic rates were determined by clonogenic survival assay, CCK-8 assay, and flow cytometry analysis, respectively. The relationships of HOTAIR, miR-93, and ATG12 were tested by bioinformatics analysis and luciferase reporter assay. Mouse xenograft tumor models were established to investigate the influence of HOTAIR knockdown on CRC radioresistance in vivo. We found that HOTAIR expression was markedly upregulated in plasma from CRC patients after radiotherapy and CRC cells after irradiation. HOTAIR knockdown, miR-93 overexpression, or ATG12 silencing weakened cell viability, induced cell apoptosis, inhibited cell autophagy, and enhanced cell radiosensitivity in CRC. HOTAIR exerted its functions by downregulating miR-93. Moreover, HOTAIR functioned as a molecular sponge of miR-93 to regulate ATG12 expression. ATG12 protein expression was markedly upregulated and associated with miR-93 and HOTAIR expression in CRC tissues. Furthermore, HOTAIR knockdown enhanced radiosensitivity of CRC xenograft tumors by regulating miR-93/ATG12 axis. In conclusion, HOTAIR knockdown potentiated radiosensitivity through regulating miR-93/ATG12 axis in CRC, further elucidating the roles and molecular basis of HOTAIR in CRC radioresistance.
| S-EPMC7060216 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) refer to a group of RNAs that are usually more than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs are involved in different regulatory processes, such as regulation of gene expression. Different lncRNAs exist throughout the genome. LncRNAs are also known for their roles in different human diseases such as cancer. HOTAIR is an lncRNA that plays a role as an oncogenic molecule in different cancer cells, such as breast, gastric, colorectal, and cervical cancer cells. Therefore, HOTAIR expression level is a potential biomarker for diagnostic and therapeutic purposes in several cancers. This RNA takes part in epigenetic regulation of genes and plays an important role in different cellular pathways by interacting with Polycomb Repressive Complex 2 (PRC2). In this review, we describe the molecular function and regulation of HOTAIR and its role in different types of cancers.
| S-EPMC4383848 | biostudies-other
Project description:A recent study characterized the long non-coding RNA (lncRNA) ELF3-antisense RNA 1 (ELF3-AS1) as an oncogenic lncRNA in bladder cancer. The present study aimed to investigate the role of ELF3-AS1 in osteosarcoma (OS). It was found that ELF3-AS1 was upregulated in OS tissues, and ELF3-AS1 expression level increased with increasing clinical stage. In OS tissues, Kruppel-like factor 12 (KLF12) was positively correlated with ELF3-AS1, while microRNA (miR)-205 was negatively correlated with ELF3-AS1. ELF3-AS1 overexpression resulted in the upregulation of KLF12, but the downregulation of miR-205. Overexpression of miR-205 caused downregulation of KLF12, but had no significant effects on ELF3-AS1 expression. Overexpression of KLF12 showed no significant impact on ELF3-AS1 and miR-205. ELF3-AS1 and KLF12 overexpression resulted in an increased proliferation rate in OS cells, while miR-205 played an opposite role and attenuated the effects of ELF3-AS1 overexpression. ELF3-AS1 overexpression promoted the methylation of the miR-205 gene. Therefore, ELF3-AS1 may promote OS cell proliferation by upregulating KLF12 through the methylation of the miR-205 gene.
| S-EPMC7039168 | biostudies-literature
Project description:A number of recent studies have focused on the association between long non-coding RNAs (lncRNAs) and cancer. HOX transcript antisense RNA (HOTAIR), an lncRNA that functions as a transcriptional modulator, has been implicated in various fundamental biological activities. HOTAIR mediates the trimethylation of histone H3 at lysine 27 and the demethylation of histone H3 dimethyl Lys4 by recruiting the polycomb repressive complex 2 and the lysine-specific demethylase 1/co-repressor of RE1-silencing transcription factor (coREST)/REST complex to the target gene promoters, which leads to gene silencing. Overexpression of HOTAIR in hepatocellular carcinoma (HCC) is strongly associated with an unfavorable prognosis for patients with HCC. HOTAIR promotes the carcinogenic activity of HCC cells through the suppression of RNA binding motif protein 38, triggering the epithelial-mesenchymal transition, and by interacting with microRNAs that act as tumor suppressors. In the present review, the role of the lncRNA HOTAIR in HCC is examined. The potential use of HOTAIR as a biomarker to achieve more accurate prognostic predictions and as an effective therapeutic target for HCC is then discussed.
| S-EPMC5529952 | biostudies-other
Project description:Long non-coding RNA has been involved in cancer progression, and high HOX transcript antisense intergenic RNA (HOTAIR) is thought to be a poor prognostic indicator in tumorigenesis of multiple types of cancer. Hence, the present study further reveals its prognostic value in tumor malignancy. A systematic review of PubMed and Web of Science was carried out to select literatures relevant to the correlation between HOTAIR expression levels and clinical outcome of various tumors. Overall survival (OS), metastasis-free survival (MFS), recurrence-free survival (RFS), and disease-free survival (DFS) were subsequently analyzed. Data from studies directly reporting a hazard ratio (HR) and the corresponding 95% confidence interval (CI) or a P value as well as survival curves were pooled in the current meta-analysis. A total of 2255 patients from 19 literatures almost published in 2011 or later were included in the analysis. The results suggest that HOTAIR was highly associated with HR for OS of 2.33 (95%CI = 1.77-3.09, Pheterogeneity = 0.016). Stratified analyses indicate that elevated levels of HOTAIR appears to be a powerful prognostic biomarker for patients with colorectal cancer (HR = 3.02, 95CI% = 1.84-4.95, Pheterogeneity = 0.699) and esophageal squamous cell carcinomas (HR = 2.24, 95CI% = 1.67-3.01, Pheterogeneity = 0.711), a similar effect was also observed in analysis method and specimen, except for ethnicity. In addition, Hazard ratios for up-regulation of HOTAIR for MFS, RFS, and DFS were 2.32 (P<0.001), 1.98 (P = 0.369), and 3.29 (P = 0.001), respectively. In summary, the high level of HOTAIR is intimately associated with an adverse OS in numerous cancers, suggesting that HOTAIR may act as a potential biomarker for the development of malignancies.
| S-EPMC4193855 | biostudies-literature