LncRNA MTX2-6 Suppresses Cell Proliferation by Acting as ceRNA of miR-574-5p to Accumulate SMAD4 in Esophageal Squamous Cell Carcinoma.
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ABSTRACT:
SUBMITTER: Li J
PROVIDER: S-EPMC8044847 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe competitive endogenous RNA (ceRNA) mechanism has been discovered recently and regulating cancer-related gene expressions. The ceRNA network participates in multiple processes, such as cell proliferation and metastasis, and potentially drives the progression of cancer. In this study, we focus on the ceRNA networks of esophageal squamous cell carcinoma and discovered a novel biomarker panel for cancer prognosis.MethodsRNA expression data of esophageal carcinoma from the TCGA database were achieved and constructed ceRNA network in esophageal carcinoma using R packages.ResultsFour miRNAs were discovered as the core of the ceRNA model, including miR-93, miR-191, miR-99b, and miR-3615. Moreover, we constructed a ceRNA network in esophageal carcinoma, which included 4 miRNAs and 6 lncRNAs. After ceRNA network modeling, we investigated six lncRNAs which could be taken together as a panel for prognosis prediction of esophageal cancer, including LINC02575, LINC01087, LINC01816, AL136162.1, AC012073.1, and AC117402.1. Finally, we tested the predictive power of the panel in all TCGA samples.ConclusionsOur study discovered a new biomarker panel which may have potential values in the prediction of prognosis of esophageal carcinoma.
| S-EPMC8486540 | biostudies-literature
Project description:We investigated the role of long non-coding RNA (lncRNA) LOC146880 in esophageal squamous cell carcinoma (ESCC). LOC146880 was significantly upregulated in ESCC tissues (n = 21) and cell lines compared to the corresponding controls. Higher LOC146880 expression correlated with poorer overall survival (OS) of ESCC patients. Moreover, CREB-binding protein (CBP) and H3K27 acetylation levels were significantly higher in the LOC146880 promoter in ESCC cell lines than in the controls. LOC146880 silencing inhibited in vitro proliferation, invasion, migration, and epithelial-mesenchymal transition of ESCC cells. LOC146880 silencing also induced G1-phase cell cycle arrest and apoptosis in ESCC cells. Bioinformatics analysis, dual luciferase reporter assays, and RNA immunoprecipitation assays showed that LOC146880 regulates FSCN1 expression in ESCC cells by sponging miR-328-5p. Moreover, FSCN1 expression correlated with activation of the MAPK signaling pathway in ESCC cells and tissues. In vivo xenograft tumor volume and liver metastasis were significantly reduced in nude mice injected with LOC146880-silenced ESCC cells as compared to those injected with control shRNA-transfected ESCC cells. These findings show that the LOC146880/miR-328-5p/FSCN1/MAPK axis regulates ESCC progression in vitro and in vivo. LOC146880 is thus a promising prognostic biomarker and potential therapeutic target in ESCC.
| S-EPMC8202886 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) are reported act as important regulators in various types of cancer. LncRNA JPX was identified as an oncogenic regulator in lung cancer. However, the function of JPX in the progression of esophageal squamous cell carcinoma (ESCC) remains unclear. In the present study, we found JPX was highly expressed in esophageal tissue from ESCC patients. Functional assays demonstrated that JPX promoted ESCC cell proliferation, migration, and invasion in vitro, and accelerated tumor growth in vivo. Mechanistically, the results showed that JPX functioned as a sponge of miR-516b-5p, which targeted vascular endothelial growth factor A (VEGFA) in ESCC cells. Interactions between miR-516b-5p and JPX or VEGFA were confirmed by luciferase reporter assays. Inhibition of JPX significantly attenuated the cell growth and mobility ability of ESCC cells in vitro. In addition, overexpression of miR-516b-5p abrogated JPX-enhanced proliferation, migration, invasion, and angiogenesis of ESCC cells. Our study demonstrated that JPX played an important role in promoting ESCC progression via the miR-516b-5p/VEGFA pathway, which might serve as a promising novel diagnostic biomarker and therapeutic target for ESCC in clinic.
| S-EPMC9179376 | biostudies-literature
Project description:BackgroundDysregulated non-coding RNAs exhibit critical functions in various cancers. Nonetheless, the levels and corresponding functions of cirCSNX14 in esophageal squamous cell carcinoma (ESCC) yet remain to be elucidated.MethodsInitially, the aberrant low levels of lncRNA-LET within ESCC tissues are validated via qRT-PCR observations. Moreover, the effects of lncRNA-LET upregulation on cell proliferation in vitro are determined. In addition, a series of assays determining the mechanistic views related to metabolism is conducted. Furthermore, the effects of lncRNA-LET in affecting tumor growth are investigated in vivo in a mouse model. Moreover, the interactions between lncRNA-LET and its networks are predicted and determined by RNA immunoprecipitation-assisted qRT-PCR as well as luciferase reporter assays.ResultsThe downregulation of lncRNA-LET is correlated to the poor prognosis of ESCC patients. Moreover, the upregulated expression of lncRNA-LET could have reduced the cell viability. In vivo tumor inhibition efficacy assays showed that an increase of lncRNA-LET presented excellent inhibitory effects on cancer proliferation as reflected by tumor weight and volume in mice. Finally, the mechanistic views regarding the effects of miR-106b-5p or miR-93-5p and SOCS4 on ESCC are related to the feedback of lncRNA-LET.ConclusionCollectively, this study suggested that lncRNA-LET miR-93-5p or the miR-106b-5p-SOCS4 axis may provide great potential in establishing ESCC therapy.
| S-EPMC9127425 | biostudies-literature
Project description:Long non‑coding RNAs (lncRNAs) and microRNAs (miRNAs) are essential for the progression of tumors, including cutaneous squamous cell carcinoma (CSCC). The present study aimed to examine the competing endogenous RNA (ceRNA) network in CSCC. Differentially expressed genes in CSCC were analyzed using the GSE66359 microarray data set, and the upstream miRNAs and lncRNAs were predicted using online database analysis (TargetScan 7.1, mirDIP 4.1, miRSearch V3.0, miRDB and RNA22 2.0) and were verified in clinical tissues. RNA pull‑down and dual luciferase reporter gene assays were used to verify the targeting relationships among lncRNA human histocompatibility leukocyte antigen complex P5 (HCP5), miR‑138‑5p and enhancer of zeste homolog 2 (EZH2). Cell lines with a high and low HCP5 expression were screened, and a pcDNA‑3.1‑HCP5 overexpression vector, small interfering RNA against HCP5, miR‑138‑5p mimics and miR‑138‑5p inhibitors were transfected into the CSCC cells. Cell viability, invasion, migration, apoptotic rate and autophagy were evaluated. The effects of HCP5 on autophagy and apoptosis of CSCC cells were verified in vivo using Ki67 and TUNEL staining. EZH2 was demonstrated to be upregulated in CSCC cells. miR‑138‑5p target sequences were identified in HCP5 and EZH2. HCP5 was revealed to function as a putative ceRNA of miR‑138‑5p to positively regulate EZH2, and EZH2 was shown to regulate autophagy and apoptosis of CSCC cells through the STAT3/VEGFR2 pathway. HCP5 overexpression decreased miR‑138‑5p levels, increased EZH2 levels and promoted cell malignant behaviors and autophagy but decreased the apoptosis rate. These trends were opposite when HCP5 was silenced. In conclusion, HCP5 may competitively bind to miR‑138‑5p to regulate EZH2 in CSCC cells, promoting autophagy and reducing apoptosis through the STAT3/VEGFR2 pathway. This study may provide a new perspective for understanding the molecular mechanism and treatment of CSCC.
| S-EPMC8253586 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) are being found to play an increasingly important role in the development of tumors. However, their biological functions and the underlying mechanisms remain unclear. Using information from GEO Datasets, we found that the lncRNA LINC00588 was downregulated in osteosarcoma (OS) in bone but was upregulated in the metastatic tumor present in the lung. We assessed the function of LINC00588 using both overexpression and knock-out studies. We performed colony formation assay, CCK-8 assay, flow cytometry, wound healing assay, transwell assay, and RT-qPCR assay and used a xenograft model to investigate the influence of LINC00588 on cell proliferation, viability, cell apoptosis and cycle, migration, invasion, endothelial cell function, EMT (epithelial to mesenchymal transition), and tumor growth, respectively. Overexpression of LINC00588 appeared to inhibit cell proliferation, viability, migration, invasion, endothelial cell function, EMT, and tumor growth but not apoptosis, while we got the opposite result when we knocked down LINC00588. Next, we predicted that LINC00588 bound to miRNA-1972 and significantly downregulated its expression, which we then verified through a luciferase reporter assay. Subsequently, we knocked down miR1972 and performed CCK-8 and transwell assays to demonstrate that downregulation of miRNA-1972 could substantially inhibit the viability and invasion of osteosarcoma cells. The expression of TP53 was downregulated at the protein level but not at the mRNA level after the overexpression of miRNA-1972. Taken together, our findings indicate that LINC00588 plays a role in OS development by downregulating the expression of miRNA-1972, which can, in turn, inhibit the expression of TP53. Hence, we believe that the LINC00588/miRNA-1072/TP53 axis could potentially serve as a therapeutic target or diagnostic biomarker for osteosarcoma.
| S-EPMC7107012 | biostudies-literature
Project description:BackgroundThe long non-coding (lnc) RNA activated by small nucleolar RNA host gene 16 (SNHG16), which has been reported to play a vital role in a number of different types of cancer, is a novel lncRNA. However, following an osteosarcoma (OS) study, the expression pattern, biological roles, clinical values and potential molecular mechanism of SNHG16 remain unclear. In the current study, we aimed to examine its expression and possible function in osteosarcoma (OS).MethodCell proliferation was measured by colony formation assay and Cell Counting Kit-8 (CCK-8) in vitro, and xenograft transplantation assay in vivo. Meanwhile, we used transwell chambers to test cell migration and invasion was evaluated. Cell cycle and apoptosis was evaluated by flow cytometry assay. Immunoblotting and qPCR analysis was carried out to detect protein and gene expression, respectively. Luciferase reporter assay was used to predict the potential downstream genes.ResultsThe present study demonstrated that SNHG16 is highly expressed in both the tissues of patients with OS, as well as OS cell lines, and its expression level was positively correlated with clinical stage and poor overall survival. Functional assays revealed that the depletion of SNHG16 inhibits OS growth, OS cell progression and promotes apoptosis both in vivo and in vitro. In addition, the present study revealed that microRNA-1285-3p expression levels can be decreased by SNHG16 acting as a 'sponge', and that this pathway takes part in OS tumor growth in vivo, and OS cell proliferation, invasion, migration and apoptosis in vitro.ConclusionsThe results from the present study demonstrate the role of lncRNA SNHG16 in OS progression, which is SNHG16 might exert oncogenic role in osteosarcoma (OS) by acting as a ceRNA of miR-1285-3p, and it may become a novel target in OS therapy.
| S-EPMC8022398 | biostudies-literature
Project description:Dysregulation of microRNAs (miRNAs) has been associated with malignant behavior in a variety of cancers. Our previous study demonstrated that miRNA expression profiles are predictors for patients with advanced non-small cell lung cancer (NSCLC). We also showed that miRNAs are involved in small-cell lung cancer metastasis. Here, we used qRT-PCR to re-analyze our previous microarray results using serum samples from 75 patients with NSCLC. Surprisingly, we found that miR-574-5p and miR-874 were overexpressed in patients with metastatic advanced NSCLC but not in patients with non-metastatic advanced NSCLC. Additionally, miR-574-5p expression was correlated between matched serum and tissue samples from 68 patients. However, these 2 miRNAs are not prognostic factors for NSCLC. Transwell and wound-healing assays showed that miR-574-5p promotes the migration and invasion of NSCLC cells. Furthermore, miR-574-5p enhanced the tyrosine phosphorylation of β-catenin by repressing PTPRU expression in vitro. In conclusion, this study explored the expression of miR-574-5p in clinical samples and its molecular mechanisms in the metastasis of advanced NSCLC.
| S-EPMC5071770 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) are emerging as important regulators of the processes involved in cancer development and progression. The molecular mechanism by which lncRNAs regulate the progression of osteosarcoma has not been clearly elucidated. The role of NR_136400, which is an uncharacterized lncRNA, has not been previously reported in osteosarcoma (OS). In the present study, we demonstrated that NR_136400 was downregulated in OS cells and that its downregulation promoted OS cell proliferation, apoptosis, and invasion. NR_136400 downregulation facilitated EMT by inhibiting the expression of E-cadherin and elevating the expression of ZEB1, Snail, and fibronectin. In vivo experiments using a xenograft tumor mouse model revealed that NR_136400 downregulation promoted tumor growth in OS. Mechanistic investigations demonstrated that NR_136400 competitively bound to miR-8081 and then upregulated the protein expression of TUSC5. Taken together, a newly identified regulatory mechanism of the lncRNA NR_136400/miR-8081/TUSC5 axis was systematically studied in OS, providing a promising target for therapeutic treatment.
| S-EPMC7242660 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) can regulate gene expression at different levels and are widely participate in various physiological and pathological processes. Emerging evidences suggests that a number of differentially expressed lncRNAs are involved in tumorigenesis. However, the function and expression regulation of a vast majority of these unique RNAs is little known. Here, we found that the lncRNA Ras suppressor protein 1 pseudogene 2 (RSU1P2) is upregulateded in cervical cancer tissues and has a tumour-promoting role. We revealed that RSU1P2 acts as a competitive endogenous RNA (ceRNA) through regulating the expression of IGF1R, N-myc and EphA4. The mechanism of this regulation is via competition for the shared microRNA let-7a. This competition promotes the malignant phenotype of cervical carcinoma cells. The transcription factor N-myc forms a positive feedback loop with RSU1P2 by in turn activating its expression, thereby enhancing its oncogenic capacity. Hence, cancer-selective targeting of RSU1P2 could have strong benefits.
| S-EPMC5546439 | biostudies-literature