scholarly journals Long noncoding RNA SGO1-AS1 inactivates TGFβ signaling by facilitating TGFB1/2 mRNA decay and inhibits gastric carcinoma metastasis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Donglan Huang ◽  
Ke Zhang ◽  
Wenying Zheng ◽  
Ruixin Zhang ◽  
Jiale Chen ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Noncoding Rna ◽  
Mrna Decay ◽  
Expression Profiles ◽  
Regulatory Mechanisms ◽  
Mesenchymal Transition ◽  
Lncrna Expression ◽  
Carcinoma Metastasis

Abstract Background Although thousands of long noncoding RNAs (lncRNAs) have been annotated, only a few lncRNAs have been characterized functionally. In this study, we aimed to identify novel lncRNAs involved in the progression of gastric carcinoma (GC) and explore their regulatory mechanisms and clinical significance in GC. Methods A lncRNA expression microarray was used to identify differential lncRNA expression profiles between paired GCs and adjacent normal mucosal tissues. Using the above method, the lncRNA SGO1-AS1 was selected for further study. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH) were performed to detect SGO1-AS1 expression in GC tissues. Gain-of-function and loss-of-function analyses were performed to investigate the functions of SGO1-AS1 and its upstream and downstream regulatory mechanisms in vitro and in vivo. Results SGO1-AS1 was downregulated in gastric carcinoma tissues compared to adjacent normal tissues, and its downregulation was positively correlated with advanced clinical stage, metastasis status and poor patient prognosis. The functional experiments revealed that SGO1-AS1 inhibited GC cell invasion and metastasis in vitro and in vivo. Mechanistically, SGO1-AS1 facilitated TGFB1/2 mRNA decay by competitively binding the PTBP1 protein, resulting in reduced TGFβ production and, thus, preventing the epithelial-to-mesenchymal transition (EMT) and metastasis. In addition, in turn, TGFβ inhibited SGO1-AS1 transcription by inducing ZEB1. Thus, SGO1-AS1 and TGFβ form a double-negative feedback loop via ZEB1 to regulate the EMT and metastasis. Conclusions SGO1-AS1 functions as an endogenous inhibitor of the TGFβ pathway and suppresses gastric carcinoma metastasis, indicating a novel potential target for GC treatment.

scholarly journals Long Noncoding RNA SGO1-AS1 Inactivates TGFβ Signaling by Facilitating TGFB mRNA Decay and Inhibits Gastric Carcinoma Metastasis

2021 ◽  
Author(s):  
Donglan Huang ◽  
Ke Zhang ◽  
Wenying Zheng ◽  
Ruixin Zhang ◽  
Jiale Chen ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Noncoding Rna ◽  
Mrna Decay ◽  
Expression Profiles ◽  
Regulatory Mechanisms ◽  
Mesenchymal Transition ◽  
Lncrna Expression ◽  
Carcinoma Metastasis

Abstract Background: Although thousands of long noncoding RNAs (lncRNAs) have been annotated, only a limited number of them have been characterized functionally. In this study, we aimed to identify novel lncRNAs involved in the progression of gastric carcinoma (GC) and explore their regulatory mechanisms and clinical significance in GC.Methods: LncRNA expression microarray was used to identify differential lncRNA expression profiles between paired GCs and adjacent normal mucosa tissues. Using the above method, lncRNA SGO1-AS1 was picked out for further study. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH) were performed to detect SGO1-AS1 expression in GC tissues. Gain-of-function and loss-of-function analyses were performed to investigate the functions of SGO1-AS1 and its upstream and downstream regulatory mechanisms in vitro and in vivo. Results: SGO1-AS1 was downregulated in gastric carcinoma tissues compared to adjacent normal tissues, and its downregulation was positively correlated with advanced clinical stage, metastasis status and poor patient prognosis. Functional experiments revealed that SGO1-AS1 inhibited GC cell invasion and metastasis in vitro and in vivo. Mechanistically, SGO1-AS1 facilitated TGFB1/2 mRNA decay by competitively binding the PTBP1 protein, which resulted in reduced TGFβ production and thus prevented the epithelial-to-mesenchymal transition (EMT) and metastasis. In addition, TGFβ in turn could inhibited SGO1-AS1 transcription by inducing ZEB1. Thus, SGO1-AS1 and TGFβ form a double-negative feedback loop via ZEB1 to regulate EMT and metastasis.Conclusions: SGO1-AS1 functions as an endogenous inhibitor of the TGFβ pathway and suppresses gastric carcinoma metastasis, indicating a novel potential target for GC treatment.

scholarly journals Hypoxia downregulated miR-4521 suppresses gastric carcinoma progression through regulation of IGF2 and FOXM1

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Shan Xing ◽  
Zhi Tian ◽  
Wenying Zheng ◽  
Wenjuan Yang ◽  
Nan Du ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Clinical Stage ◽  
Xenograft Model ◽  
Regulatory Mechanisms ◽  
Mesenchymal Transition ◽  
Mouse Xenograft Model

Abstract Background MicroRNAs (miRNAs) show considerable promise as therapeutic agents to improve tumor treatment, as they have been revealed as crucial modulators in tumor progression. However, our understanding of their roles in gastric carcinoma (GC) metastasis is limited. Here, we aimed to identify novel miRNAs involved in GC metastasis and explored their regulatory mechanisms and therapeutic significance in GC. Methods The microRNA expression profiles of GC tumors at different stages and at different metastasis statuses were compared respectively using the stomach adenocarcinoma (STAD) miRNASeq dataset in TCGA. Using the above method, miR-4521 was picked out for further study. miR-4521 expression in GC tissues was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). Highly and lowly invasive cell sublines were established using a repetitive transwell assay. Gain-of-function and loss-of-function analyses were performed to investigate the functions of miR-4521 and its upstream and downstream regulatory mechanisms in vitro and in vivo. Moreover, we investigated the therapeutic role of miR-4521 in a mouse xenograft model. Results In this study, we found that miR-4521 expression was downregulated in GC tissues compared with adjacent normal tissues and that its downregulation was positively correlated with advanced clinical stage, metastasis status and poor patient prognosis. Functional experiments revealed that miR-4521 inhibited GC cell invasion and metastasis in vitro and in vivo. Further studies showed that hypoxia repressed miR-4521 expression via inducing ETS1 and miR-4521 mitigated hypoxia-mediated metastasis, while miR-4521 inactivated the AKT/GSK3β/Snai1 pathway by targeting IGF2 and FOXM1, thereby inhibiting the epithelial-mesenchymal transition (EMT) process and metastasis. In addition, we demonstrated that therapeutic delivery of synthetic miR-4521 suppressed gastric carcinoma progression in vivo. Conclusions Our results suggest an important role for miR-4521 in regulating GC metastasis and hypoxic response of tumor cells as well as the therapeutic significance of this miRNA in GC.

lncRNA CTBP1-AS2 promotes proliferation and migration of glioma by modulating miR-370-3p–Wnt7a-mediated epithelial–mesenchymal transition

2020 ◽  
Vol 98 (6) ◽  
pp. 661-668
Author(s):  
Yongfeng Li ◽  
Jin Zong ◽  
Cong Zhao
Keyword(s):  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Luciferase Assay ◽  
Mesenchymal Transition ◽  
Tumor Tissues ◽  
And Migration ◽  
Proliferation And Migration

Glioma is one of the most common and aggressive malignant primary brain tumors, with a poor 5-year survival rate. The long noncoding RNA (lncRNA) CTBP1-AS2 has been shown to be correlated with the prognosis of cancer, but the role of CTBP1-AS2 in glioma and its concrete mechanism is fully unknown. The clinical data and tissues of glioma patients were analyzed. Cell viability and migration assays were performed. Western blotting and qRT-PCR were adopted for investigation of target protein expressions. Double luciferase assay was used to investigate the interaction between different elements. The lncRNA CTBP1-AS2 had increased expression profiles in tumor tissues, which is associated with poor prognosis. In detail, CTBP1-AS2 knockdown decreased proliferation and migration phenotypes in both U87-MG and LN229 cells. Moreover, CTBP1-AS2 knockdown suppressed the key epithelial–mesenchymal transition (EMT) markers by downregulating Wnt7a-mediated signaling. Furthermore, miR-370-3p functioned as a link that could be absorbed by CTBP1-AS2, thus regulating Wnt7a expression. Lastly, the CTBP1-AS2–miR-370-3p–Wnt7a axis modulated EMT in glioma cells in vitro and in vivo. This study provides new insights that a novel lncRNA, CTBP1-AS2, regulates EMT of glioma by modulating the miR-370-3p–Wnt7a axis.

scholarly journals Long Non-coding RNA LINC01969 Promotes Ovarian Cancer by Regulating the miR-144-5p/LARP1 Axis as a Competing Endogenous RNA

2021 ◽  
Vol 8 ◽  
Author(s):  
Jinxin Chen ◽  
Xiaocen Li ◽  
Lu Yang ◽  
Jingru Zhang
Keyword(s):  
Ovarian Cancer ◽  
Rna Binding ◽  
Expression Profiles ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Lncrna Expression ◽  
Qrt Pcr

Accumulating evidence has shown that long non-coding RNAs (lncRNAs) can be used as biological markers and treatment targets in cancer and play various roles in cancer-related biological processes. However, the lncRNA expression profiles and their roles and action mechanisms in ovarian cancer (OC) are largely unknown. Here, we assessed the lncRNA expression profiles in OC tissues from The Cancer Genome Atlas (TCGA) database, and one upregulated lncRNA, LINC01969, was selected for further study. LINC01969 expression levels in 41 patients were verified using quantitative real-time polymerase chain reaction (qRT-PCR). The in vitro effects of LINC01969 on OC cell migration, invasion, and proliferation were determined by the CCK-8, ethynyl-2-deoxyuridine (EdU), wound healing, and Transwell assays. Epithelial–mesenchymal transition (EMT) was evaluated using qRT-PCR and Western blotting. The molecular mechanisms of LINC01969 in OC were assessed through bioinformatics analysis, RNA-binding protein immunoprecipitation (RIP), dual luciferase reporter gene assays, and a rescue experiment. Finally, in vivo experiments were conducted to evaluate the functions of LINC01969. The results of the current study showed that LINC01969 was dramatically upregulated in OC, and patients with lower LINC01969 expression levels tended to have better overall survival. Further experiments demonstrated that LINC01969 promoted the migration, invasion, and proliferation of OC cells in vitro and sped up tumor growth in vivo. Additionally, LINC01969, which primarily exists in the cytoplasm, boosted LARP1 expression by sponging miR-144-5p and promoted the malignant phenotypes of OC cells. In conclusion, the LINC01969/miR-144-5p/LARP1 axis is a newly identified regulatory signaling pathway involved in OC progression.

scholarly journals Long noncoding RNA LINC00941 promotes pancreatic cancer progression by competitively binding miR-335-5p to regulate ROCK1-mediated LIMK1/Cofilin-1 signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jie Wang ◽  
Zhiwei He ◽  
Jian Xu ◽  
Peng Chen ◽  
Jianxin Jiang
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Cell Lines ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Loss Of Function ◽  
Mesenchymal Transition

AbstractAn accumulation of evidence indicates that long noncoding RNAs are involved in the tumorigenesis and progression of pancreatic cancer (PC). In this study, we investigated the functions and molecular mechanism of action of LINC00941 in PC. Quantitative PCR was used to examine the expression of LINC00941 and miR-335-5p in PC tissues and cell lines, and to investigate the correlation between LINC00941 expression and clinicopathological features. Plasmid vectors or lentiviruses were used to manipulate the expression of LINC00941, miR-335-5p, and ROCK1 in PC cell lines. Gain or loss-of-function assays and mechanistic assays were employed to verify the roles of LINC00941, miR-335-5p, and ROCK1 in PC cell growth and metastasis, both in vivo and in vitro. LINC00941 and ROCK1 were found to be highly expressed in PC, while miR-335-5p exhibited low expression. High LINC00941 expression was strongly associated with larger tumor size, lymph node metastasis, and poor prognosis. Functional experiments revealed that LINC00941 silencing significantly suppressed PC cell growth, metastasis and epithelial–mesenchymal transition. LINC00941 functioned as a molecular sponge for miR-335-5p, and a competitive endogenous RNA (ceRNA) for ROCK1, promoting ROCK1 upregulation, and LIMK1/Cofilin-1 pathway activation. Our observations lead us to conclude that LINC00941 functions as an oncogene in PC progression, behaving as a ceRNA for miR-335-5p binding. LINC00941 may therefore have potential utility as a diagnostic and treatment target in this disease.

LncRNA SNHG4 promotes the proliferation, migration, invasiveness, and epithelial–mesenchymal transition of lung cancer cells by regulating miR-98-5p

2019 ◽  
Vol 97 (6) ◽  
pp. 767-776 ◽  
Author(s):  
Yufu Tang ◽  
Lijian Wu ◽  
Mingjing Zhao ◽  
Guangdan Zhao ◽  
Shitao Mao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Lung Cancer Cells ◽  
Mesenchymal Transition ◽  
Gene 4

Long noncoding RNA small nucleolar RNA host gene 4 (SNHG4) is usually up-regulated in cancer and regulates the malignant behavior of cancer cells. However, its role in lung cancer remains elusive. In this study, we silenced the expression of SNHG4 in NCI-H1437 and SK-MES-1, two representative non-small-cell lung cancer cell lines, by transfecting them with siRNA (small interfering RNA) that specifically targets SNHG4. We observed significantly inhibited cell proliferation in vitro and reduced tumor growth in vivo after SNHG4 silencing. SNHG4 knockdown also led to cell cycle arrest at the G1 phase, accompanied with down-regulation of cyclin-dependent kinases CDK4 and CDK6. The migration and invasiveness of these two cell lines were remarkably inhibited after SNHG4 silencing. Moreover, our study revealed that the epithelial–mesenchymal transition (EMT) of lung cancer cells was suppressed by SNHG4 silencing, as evidenced by up-regulated E-cadherin and down-regulated SALL4, Twist, and vimentin. In addition, we found that SNHG4 silencing induced up-regulation of miR-98-5p. MiR-98-5p inhibition abrogated the effect of SNHG4 silencing on proliferation and invasion of lung cancer cells. In conclusion, our findings demonstrate that SNHG4 is required by lung cancer cells to maintain malignant phenotype. SNHG4 probably exerts its pro-survival and pro-metastatic effects by sponging anti-tumor miR-98-5p.

scholarly journals Investigation and Identification of let-7a Related Functional Proteins in Gastric Carcinoma by Proteomics

2012 ◽  
Vol 35 (4) ◽  
pp. 285-295 ◽  
Author(s):  
Yimin Zhu ◽  
Xingyuan Xiao ◽  
Lairong Dong ◽  
Zhiming Liu
Keyword(s):  
Gastric Carcinoma ◽  
Noncoding Rna ◽  
Target Genes ◽  
Rho Gtpase ◽  
Two Dimensional Gel Electrophoresis ◽  
Gastric Carcinoma Cell ◽  
Rna Molecules ◽  
Small Noncoding Rna

MicroRNAs are small noncoding RNA molecules that control expression of target genes. Our previous studies show that let-7a decreased in gastric carcinoma and that up-regulation of let-7a by gene augmentation inhibited gastric carcinoma cell growth bothin vitroandin vivo, whereas it remains largely unclear as to how let-7a affects tumor growth. In this study, proteins associated with the function of let-7a were detected by high throughout screening. The cell line of SGC-7901 stablely overexpressing let-7a was successfully established by gene cloning. Two-dimensional gel electrophoresis (2-DEy was used to separate the total proteins of SGC-7901/let-7a, SGC-7901/EV and SGC-7901, and PDQuest software was applied to analyze 2-DE images. Ten different protein spots were identified by MALDI-TOF-MS, and they may be the proteins associated with let-7a function. The overexpressed proteins included Antioxidant protein 2, Insulin–like growth factor binding protein 2, Protein disulfide isomerase A2, C-1-tetrahydrofolate synthase, Cyclin-dependent kinase inhibitor1 (CDKN1) and Rho–GTPase activating protein 4. The underexpressed proteins consisted of S-phase kinase-associated protein 2 (Spk2), Platelet membrane glycoprotein, Fibronectin and Cks1 protein. Furthermore, the different expression levels of the partial proteins (CDKN1, Spk2 and Fibronectin) were confirmed by western blot analysis. The data suggest that these differential proteins are involved in a novel let-7a signal pathway and these findings provide the basis to investigate the functional mechanisms of let-7a in gastric carcinoma.

scholarly journals Systematic analyses reveal long non-coding RNA (PTAF)-mediated promotion of EMT and invasion-metastasis in serous ovarian cancer

2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Haihai Liang ◽  
Xiaoguang Zhao ◽  
Chengyu Wang ◽  
Jian Sun ◽  
Yingzhun Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Expression Profiles ◽  
In Vivo Studies ◽  
Clinical Samples ◽  
Orthotopic Mouse Model ◽  
Protein Coding ◽  
Mesenchymal Transition ◽  
Protein Coding Genes

Abstract Background A deeper mechanistic understanding of epithelial-to-mesenchymal transition (EMT) regulation is needed to improve current anti-metastasis strategies in ovarian cancer (OvCa). This study was designed to investigate the role of lncRNAs in EMT regulation during process of invasion-metastasis in serous OvCa to improve current anti-metastasis strategies for OvCa. Methods We systematically analyzes high-throughput gene expression profiles of both lncRNAs and protein-coding genes in OvCa samples with integrated epithelial (iE) subtype and integrated mesenchymal (iM) subtype labels. Mouse models, cytobiology, molecular biology assays and clinical samples were performed to elucidate the function and underlying mechanisms of lncRNA PTAF-mediated promotion of EMT and invasion-metastasis in serous OvCa. Results We constructed a lncRNA-mediated competing endogenous RNA (ceRNA) regulatory network that affects the expression of many EMT-related protein-coding genes in mesenchymal OvCa. Using a combination of in vitro and in vivo studies, we provided evidence that the lncRNA PTAF-miR-25-SNAI2 axis controlled EMT in OvCa. Our results revealed that up-regulated PTAF induced elevated SNAI2 expression by competitively binding to miR-25, which in turn promoted OvCa cell EMT and invasion. Moreover, we found that silencing of PTAF inhibited tumor progression and metastasis in an orthotopic mouse model of OvCa. We then observed a significant correlation between PTAF expression and EMT markers in OvCa patients. Conclusions The lncRNA PTAF, a mediator of TGF-β signaling, can predispose OvCa patients to metastases and may serve as a potential target for anti-metastatic therapies for mesenchymal OvCa patients.

scholarly journals lncRNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression via miR-655-3p

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 931-943
Author(s):  
Yuxin Zhao ◽  
Zhaoxia Wang ◽  
Meili Gao ◽  
Xuehong Wang ◽  
Hui Feng ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Xenograft Tumor ◽  
Competing Endogenous Rna ◽  
Mesenchymal Transition ◽  
Downstream Target ◽  
Lncrna Malat1 ◽  
Xenograft Tumor Growth

Abstract Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was reported as an oncogene in many tumors including retinoblastoma (RB). This research mainly focused on the functions and mechanism of MALAT1 in RB. MALAT1 was upregulated in RB tissues and cells, and it served as a competing endogenous RNA (ceRNA) and inhibited miRNA-655-3p (miR-655-3p) expression, which eventually regulated the expression of miR-655-3p downstream target ATPase Family AAA Domain Containing 2 (ATAD2). The level of ATAD2 significantly increased, while that of miR-655-3p remarkably decreased in RB tissues and cells. MALAT1 depletion inhibited cell proliferation, metastasis, and epithelial–mesenchymal transition (EMT), but promoted apoptosis in vitro and blocked xenograft tumor growth in vivo. MALAT1 exerted its oncogenic functions in RB by regulating miR-655-3p/ATAD2 axis.

scholarly journals C1orf61 promotes hepatocellular carcinoma metastasis and affects the therapeutic response to sorafenib

2020 ◽  
Author(s):  
You Yu ◽  
Zhimeng Wang ◽  
Zan Huang ◽  
Xianying Tang ◽  
Wenhua Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Therapeutic Response ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Molecular Events ◽  
Carcinoma Metastasis ◽  
And Migration

Abstract Background C1orf61 is a specific transcriptional activator that is highly up-regulated during weeks 4–9 of human embryogenesis, the period in which most organs develop. We have previously demonstrated that C1orf61 acts as a tumor activator in human hepatocellular carcinoma (HCC) tumorigenesis and metastasis. However, the underlying molecular mechanisms of tumor initiation and progression in HCC remain obscure. Methods In this study, we demonstrated that the pattern of C1orf61 expression was closely correlated with metastasis in liver cancer cells. Gene expression profiling analysis indicated that C1orf61 regulated diverse genes related to cell growth, migration, invasion and epithelial-mesenchymal transition (EMT). Results Results showed that C1orf61 promotes hepatocellular carcinoma metastasis by inducing cellular EMT in vivo and in vitro. Moreover, C1orf61-induced cellular EMT and migration are involved in the activation of the STAT3 and Akt cascade pathways. We also found that C1orf61 was associated with HBV infection-induced cell migration in HCC. In addition, C1orf61 expression improved the efficacy of the anticancer therapy sorafenib in HCC patients. For the first time, we report a regulatory pathway by which C1orf61 promoted cancer cell metastasis and regulated the therapeutic response to sorafenib. Conclusions These findings increased our understanding of the molecular events that regulate metastasis and treatment in HCC.

Sign in / Sign up

Export Citation Format

Share Document