TMEM161B-AS1 suppresses proliferation, invasion and glycolysis by targeting miR-23a-3p/HIF1AN signal axis in oesophageal squamous cell carcinoma.
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ABSTRACT:
SUBMITTER: Shi Z
PROVIDER: S-EPMC8278070 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Accumulating evidence has shown that long noncoding RNA GAS5 is a well-known tumor suppressor in the pathogenesis of a variety of human cancers. However, the detailed role of GAS5 in osteosarcoma is still largely unclear. In this study, we found that GAS5 was downregulated in human osteosarcoma tissues and cell lines compared with matched adjacent tissues and normal osteoblast cells. Overexpression of GAS5 could significantly suppress the growth and invasion of osteosarcoma cells, while downregulation of GAS5 promoted cell proliferation and invasion. We confirmed that GAS5 could directly bind with miR-23a-3p by using luciferase reporter gene and RNA immunoprecipitation and pull-down assay. Downregulation of miR-23a-3p repressed cell proliferation and invasion. Overexpression of miR-23a-3p counterbalanced the inhibition effect of GAS5 on cell proliferation and invasion. Further studies indicated that overexpression of GAS5 inhibited cell proliferation and metastasis by regulating phosphatase and tensin homolog (PTEN). PTEN was authenticated as a target of miR-23a-3p. Upregulation of GAS5 or silence of miR-23a-3p increased the level of PTEN, while downregulation of GAS5 or overexpression of miR-23a-3p suppressed the expression of PTEN. In addition, overexpression of GAS5 could neutralize the effect of downregulating PTEN on osteosarcoma cell functions. We proved that GAS5 regulated the viability and invasion of osteosarcoma cells through the PI3K/AKT pathway. Moreover, overexpression of GAS5 could inhibit tumor growth in a xenograft nude mouse model in vivo. In summary, GAS5 functions as a competing endogenous RNA, sponging miR-23a-3p, to promote PTEN expression and suppress cell growth and invasion in osteosarcoma by regulating the PI3K/AKT pathway.
| S-EPMC7784500 | biostudies-literature
Project description:Multiple studies have unveiled that long non-coding RNAs (lncRNAs) play a pivotal role in tumour progression and metastasis. However, the biological role of lncRNA ZEB1-AS1 in oesophageal squamous cell carcinoma (ESCC) remains under investigation, and thus, the current study was to investigate the functions of ZEB1-AS1 in proliferation and invasion of ESCC. Here, we discovered that ZEB1-AS1 and ZEB1 were markedly up-regulated in ESCC tissues and cells relative to their corresponding normal control. ZEB1-AS1 and ZEB1 overexpressions were both related to TNM staging and lymph node metastasis as well as poor prognosis in ESCC. The hypomethylation of ZEB1-AS1 promoter triggered ZEB1-AS1 overexpression in ESCC tissues and cells. In addition, ZEB1-AS1 knockdown mediated by siRNA markedly suppressed the proliferation and invasion in vitro in EC9706 and TE1 cells, which was similar with ZEB1 siRNA treatment, coupled with EMT alterations including the up-regulation of E-cadherin level as well as the down-regulation of N-cadherin and vimentin levels. Notably, ZEB1-AS1 depletion dramatically down-regulated ZEB1 expression in EC9706 and TE1 cells, and ZEB1 overexpression obviously reversed the inhibitory effects of proliferation and invasion triggered by ZEB1-AS1 siRNA. ZEB1-AS1 shRNA evidently inhibited tumour growth and weight, whereas ZEB1 elevation partly recovered the tumour growth in ESCC EC9706 and TE1 xenografted nude mice. In conclusion, ZEB1-AS1 overexpression is tightly involved in the development and progression of ESCC, and it exerts the antitumour efficacy by regulating ZEB1 level in ESCC.
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Project description:Long non‑coding RNAs (lncRNAs) are widely studied in cancer pathogenesis. Accumulating evidence has demonstrated that lncRNAs are involved in the cellular progression of colorectal cancer (CRC). However, the regulatory mechanism of lncRNA TMPO‑antisense (AS)1 in CRC has not been fully elucidated. The present study aimed to elucidate the role and regulatory mechanisms of lncRNA TMPO‑AS1 in CRC. In the present study, the expression levels of TMPO‑AS1 and microRNA‑143‑3p (miR‑143‑3p) were detected using reverse transcription‑quantitative PCR assay. The relative protein expression levels were measured via western blot analysis. MTT and Transwell assays were used to determine cell proliferation, migration and invasion, while a luciferase reporter assay was performed to assess the relationship between TMPO‑AS1 and miR‑143‑3p. In addition, a tumor animal model was used to investigate the effect of TMPO‑AS1 on tumor growth in CRC in vivo. TMPO‑AS1 expression was increased and miR‑143‑3p expression was decreased in CRC cells. TMPO‑AS1 knockdown and miR‑143‑3p overexpression significantly inhibited cell proliferation, migration and invasion of CRC cells. Luciferase reporter assay results demonstrated that miR‑143‑3p was a direct target of TMPO‑AS1. Inhibition of miR‑143‑3p could alleviate the suppressive effects of TMPO‑AS1 deletion on cell proliferation, migration and invasion of CRC cells. Furthermore, TMPO‑AS1 deletion could inhibit tumor growth in CRC in vivo. It was concluded that TMPO‑AS1 regulated cell proliferation, migration and invasion of CRC cells by targeting miR‑143‑3p. These findings provided a new regulatory network and therapeutic target for the treatment of CRC.
| S-EPMC7453500 | biostudies-literature
Project description:Tamoxifen (Tam) has long been a top treatment option for breast cancer patients, but the challenge of eliminating cancer recurrence remains. Here, we identify a signalling pathway involving ELOVL2, ELOVL2-AS1, and miR-1233-3p, which contributes to drug resistance in Tam-resistant (TamR) breast cancer. ELOVL2-AS1, a long noncoding RNA, was significantly upregulated by its antisense gene, ELOVL2, which is known to be downregulated in TamR cells. Additionally, ELOVL2-AS1 underwent the most hypermethylation in MCF-7/TamR cells. Furthermore, patients with breast cancer who developed TamR during chemotherapy had significantly lower expression of ELOVL2-AS1 compared to those who responded to Tam. Ectopic downregulation of ELOVL2-AS1 by siRNA both stimulated cancer cell growth and deteriorated TamR. We also found that ELOVL2-AS1 sponges miR-1233-3p, which has pro-proliferative activity and elevates TamR, leading to the activation of potential target genes, such as MYEF2, NDST1, and PIK3R1. These findings suggest that ELOVL2-AS1, in association with ELOVL2, may contribute to the suppression of drug resistance by sponging miR-1233-3p in breast cancer.
| S-EPMC10621244 | biostudies-literature
Project description:Background: Considering the role of immunity and ferroptosis in the invasion, proliferation and treatment of cancer, it is of interest to construct a model of prognostic-related differential expressed immune-related ferroptosis genes (PR-DE-IRFeGs), and explore the ferroptosis-related biological processes in esophageal cancer (ESCA). Methods: Four ESCA datasets were used to identify three PR-DE-IRFeGs for constructing the prognostic model. Validation of our model was based on analyses of internal and external data sets, and comparisons with past models. With the biological-based enrichment analysis as a guide, exploration for ESCA-related biological processes was undertaken with respect to the immune microenvironment, mutations, competing endogenous RNAs (ceRNA), and copy number variation (CNV). The model's clinical applicability was measured by nomogram and correlation analysis between risk score and gene expression, and also immune-based and chemotherapeutic sensitivity. Results: Three PR-DE-IRFeGs (DDIT3, SLC2A3, and GCH1), risk factors for prognosis of ESCA patients, were the basis for constructing the prognostic model. Validation of our model shows a meaningful capability for prognosis prediction. Furthermore, many biological functions and pathways related to immunity and ferroptosis were enriched in the high-risk group, and the role of the TMEM161B-AS1/hsa-miR-27a-3p/GCH1 network in ESCA is supported. Also, the KMT2D mutation is associated with our risk score and SLC2A3 expression. Overall, the prognostic model was associated with treatment sensitivity and levels of gene expression. Conclusion: A novel, prognostic model was shown to have high predictive value. Biological processes related to immune functions, KMT2D mutation, CNV and the TMEM161B-AS1/hsa-miR-27a-3p/GCH1 network were involved in ESCA progression.
| S-EPMC8908453 | biostudies-literature
Project description:Here we showed that Osthole, 7-methoxy-8-(3-methyl-2-butenyl) coumarin, a bioactive coumarin derivative extracted from medicinal plants, inhibited migration, invasion, epithelial to mesenchymal transition (EMT) in androgen-independent prostate cancer (AIPC) cells in vitro and metastasis of AIPC in vivo. In patients, high Snail levels were correlated with a higher histological Gleason sum and poor survival rates. Osthole inhibited the TGF-?/Akt/MAPK pathways, reduced Snail-DNA-binding activity and induced E-cadherin. We found that osthole decreased miR-23a-3p. Ectopic miR-23a-3p suppressed E-cadherin 3' untranslated region reporter activity and E-cadherin expression, and relieved the motility suppression caused by osthole treatment.
| S-EPMC4673254 | biostudies-literature
Project description:Objective: For determination of how ADAMTS9-AS1/miR-301b-3p/TGFBR2/JAK STAT signaling axis modulates progression of breast cancer cells. Methods: Target lncRNA was determined by differential analysis of breast cancer expression data and survival analysis. Differentially expressed miRNAs and target mRNAs that had binding sites with target lncRNA were predicted. GSEA software was used to carry out pathway enrichment analysis for mRNAs. Binding of the researched genes were tested with RNA binding protein immunoprecipitation (RIP). How miR-301b-3p bound TGFBR2 mRNA was tested by dual-luciferase method. Transwell, colony formation, EdU approaches were employed for verification of invasion and proliferation of breast cancer cells in each treatment group. Results: Markedly inactivated ADAMTS9-AS1 in breast cancer pertained to patient's prognosis. MiR-301b-3p was capable of binding TGFBR2/ADAMTS9-AS1. However, overexpression of ADAMTS9-AS1 stimulated miR-301b-3p binding ADAMTS9-AS1 and repressed miR-301b-3p binding TGFBR2 mRNA. ADAMTS9-AS1 interference enhanced cancer proliferation and invasion, facilitated levels of KI67, PCNA, MMP-9 and MMP-2, and activated the JAK STAT signaling pathway. While silencing miR-301b-3p reversed the effect of ADAMTS9-AS1 interference. In addition, TGFBR2 interference or restraining JAK STAT signaling counteracted the effect of ADAMTS9-AS1. Conclusion: ADAMTS9-AS1 could sequester miR-301b-3p to inhibit progression of breast cancer via TGFBR2/JAK STAT pathway. This study supplies a rationale for incremental apprehension of ADAMTS9-AS1 in breast cancer progression.
| S-EPMC8652087 | biostudies-literature
Project description:BackgroundColorectal cancer (CRC) is one of the lethal cancers with a high mortality rate worldwide and understanding the mechanisms behind its progression is critical for improving patients' prognosis and developing therapeutics. MiR-500a-3p has been demonstrated to be involved in the progression of several human cancers but its role in CRC remains unclear. The aim of this study is to uncover the expression pattern and mechanisms of action of miR-500a-3p during the CRC progression.MethodsThe expression of miR-500a-3p and Cyclin-dependent kinases 6 (CDK6) in 134 CRC tissues were tested by quantitative PCR (qPCR) and immunohistochemistry staining (IHC), respectively. The effect of miR-500a-3p on cell proliferation was explored in vitro and in vivo. The glycolysis of CRC cells was determined by Mass Spectrometry and Seahorse XF 96 Extracellular Flux Analyzer. A dual-luciferase reporter assay was performed to validate the relationship between miR-500a-3p and CDK6.ResultsmiR-500a-3p was abnormally downregulated in CRC tissues and cell lines and was negatively associated with a worse prognosis. miR-500a-3p mimics impeded CRC cell proliferation in vitro and in vivo. miR-500a-3p inhibited glucose consumption, lactate and ATP production, and down-regulated the expression of hexokinase2 (HK2). In silico prediction combined with western blot and luciferase assay confirmed that CDK6 is a direct target of miR-500a-3p. Overexpression of CDK6 phenotypically rescued the inhibitory effect of miR-500a-3p on the proliferation and glycolysis of CRC cells.ConclusionsOur study revealed a potential tumor-suppressive role of miR-500a-3p in CRC, specifically targeting CDK6 and inhibiting cancer cell proliferation and aerobic glycolysis, which may provide new insights into novel prognostic biomarkers and therapeutic targets for CRC.
| S-EPMC8896266 | biostudies-literature
Project description:Glioblastoma (GBM) is one of the most prevalent and aggressive central nervous tumors with high mobility and mortality. The prognosis of patients with GBM is poor. It is therefore essential to explore the therapeutic strategies for the treatment of GBM. Previous studies have demonstrated that the long non‑coding RNA (lncRNA) Kinectin 1‑Antisense RNA 1 (KTN1‑AS1) can participate in the development of several types of cancer. However, the underlying mechanism of KTN1‑AS1 in GBM remains unknown. The present study aimed to determine the potential role of KTN1‑AS1 in GBM. In this study, reverse transcription quantitative PCR analysis was conducted and the results demonstrated that KTN1‑AS1 was upregulated in GBM tissues and cell lines compared with normal tissues and astrocytes (NHA). Furthermore, KTN1‑AS1 knockdown decreased the viability and invasive ability of glioma cells in vitro and in vivo. In addition, high level of KTN1‑AS1 was correlated with poor prognosis in TCGA GBM database. Furthermore, microRNA‑505‑3p (miR‑505‑3p) was a promising target of KTN1‑AS1, and the suppressing effects of miR‑505‑3p on cell proliferation and invasive ability was reversed by downregulating KTN1‑AS1. Taken together, the results from the present provided novel insights into the roles of KTN1‑AS1 in GBM, and suggested that the KTN1‑AS1/miR‑505‑3p axis may be considered as a novel therapeutic target for the treatment of patients with GBM.
| S-EPMC7640367 | biostudies-literature
Project description:BackgroundGlioblastoma multiforme (GBM) is the most common primary CNS tumor, characterized by high mortality and heterogeneity. However, the related lncRNA signatures and their target microRNA (miRNA) for GBM are still mostly unknown. Therefore, it is critical that we discover lncRNA markers in GBM and their biological activities.Materials and methodsGBM-related RNA-seq data were obtained from the Cancer Genome Atlas (TCGA) database. The "edger" R package was used for differently expressed lncRNAs (DELs) identification. Then, we forecasted prospective miRNAs that might bind to lncRNAs by Cytoscape software. Survival analysis of those miRNAs was examined by the starBase database, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the miRNAs' target genes was conducted by the Gene Set Enrichment Analysis (GSEA) database and R software. Moreover, the proliferative ability of unc-5 netrin receptor B antisense RNA 1 (UNC5B-AS1) cells was evaluated by Cell Counting Kit-8 (CCK-8) analysis. Mechanistically, the regulatory interaction between UNC5B-AS1 and miRNA in GBM biological processes was studied using CCK-8 analysis.ResultsOur results indicated that overexpression of UNC5B-AS1 has been shown to suppress GBM cell growth. Mechanistically, miR-24-3p in GBM was able to alleviate the anti-oncogenic effects of UNC5B-AS1 on cell proliferation.ConclusionThe discovery of the novel UNC5B-AS1-miR-24-3p network suggests possible lncRNA and miRNA roles in the development of GBM, which may have significant ramifications for the analysis of clinical prognosis and the development of GBM medications.
| S-EPMC11003007 | biostudies-literature