scholarly journals Long Noncoding RNA Linc00152 Functions as a Tumor Propellant in Pan-Cancer

2017 ◽  
Vol 44 (6) ◽  
pp. 2476-2490 ◽  
Author(s):  
Shouping Xu ◽  
Lin Wan ◽  
Huizi Yin ◽  
Hongbiao Xu ◽  
Wei Zheng ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Dna Hypomethylation ◽  
Normal Tissues ◽  
Super Enhancer ◽  
Pan Cancer

Background/Aims: The oncogenic role of linc00152 in pan-cancer is unclear. Methods: In this study, RNA-Seq of 33 breast specimens was performed, and the expression of linc00152 was validated by qPCR using 50 paired breast cancer tissues and adjacent normal tissues. This result combined with the expression of linc00152 in pan-cancer was revalidated by Gene Expression Omnibus and The Cancer Genome Atlas data. Next, the oncogenic roles of linc00152 in view of prognosis, chemoresistance, genomic and epigenetic regulation, including DNA methylation and histone modification, potential biological function enrichment, and basic molecular function in pan-cancer, were also evaluated in vitro and in vivo. Results: Linc00152 is upregulated in pan-cancer, especially in progressive cancer, and the high expression of linc00152 may lead to a worse prognosis and chemoresistance in pan-cancer patients. Amplification, DNA hypomethylation, promoter-like lncRNA characteristics and super-enhancer regulation are the drivers that lead to the upregulation of linc00152 in pan-cancer. Meanwhile, linc00152 was involved in cancer-related pathways, infection and immune response-associated pathways by enriched analysis using TCGA data. Finally, linc00152 was confirmed to promote the proliferation, migration and invasion in MDA-MB-231, SGC-7901 and 786-O. Moreover, RIP and RNA pull-down assays indicated that linc00152 can bind to EZH2 directly. Conclusion: All of the results indicated that linc00152 acted as an oncogenic propellant from various perspectives, and it may be an effective therapy target in pan-cancer.

scholarly journals Knockdown long noncoding RNA SLC8A1-AS1 attenuate cell invasion and migration in glioma via suppression of Wnt-β catenin signaling pathways

2020 ◽  
Author(s):  
Ling He ◽  
Hui Yang ◽  
Xiao-long Zhu ◽  
Yan Zhang ◽  
Kun Lv
Keyword(s):  
Noncoding Rna ◽  
Epithelial To Mesenchymal Transition ◽  
Glioma Cells ◽  
Neural System ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Validation Experiment

Abstract Background: Glioma, as the most common aggressive malignant tumor in the central nervous system, is still an insurmountable disease in neural system. The potential mechanism of its carcinogenesis remains largely unclear. Methods: In the present study, we identified dysregulated lncRNA solute carrier family 8 member A1 antisense RNA 1 (SLC8A1-AS1) as associated with glioma based on The Cancer Genome Atlas （TCGA）data. Validation experiment was conducted to confirm a high expression level of lncRNA SLC8A1-AS1 in glioma tissues. Results: Down-regulation of lncRNA SLC8A1-AS1 suppressed proliferation, clone formation, migration and invasion of glioma cells in vitro and in vivo. Moreover, lncRNA SLC8A1-AS1 silencing decreased the activity of the Wnt/β-catenin pathway and suppressed the epithelial to mesenchymal transition (EMT) in glioma cells. Conclusions: Collectively, these findings provide a novel insights into the function and mechanism of lncRNA SLC8A1-AS1 in the pathogenesis of glioma and highlight its potential as a therapeutic target for glioma intervention.

scholarly journals Long Noncoding RNA FEZF1-AS1 Promotes Osteosarcoma Progression by Regulating the miR-4443/NUPR1 Axis

2018 ◽  
Vol 26 (9) ◽  
pp. 1335-1343 ◽  
Author(s):  
Chengwei Zhou ◽  
Jianxiang Xu ◽  
Jinti Lin ◽  
Renjin Lin ◽  
Kai Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Migration And Invasion ◽  
Normal Tissues ◽  
Mg63 Cells ◽  
Tumor Growth And Metastasis ◽  
And Migration

Long noncoding RNA (lncRNA) FEZF1-AS1 was demonstrated to facilitate cell proliferation and migration in some cancers. However, the functions of FEZF1-AS1 and its molecular mechanism in osteosarcoma remain to be elucidated. In our study, we found that the expression of FEZF1-AS1 was upregulated in osteosarcoma samples and cell lines compared with normal tissues or cells. Besides, we showed that the expression levels of FEZF1-AS1 in osteosarcoma patients were positively correlated with tumor metastasis and TNM stage. Additionally, FEZF1-AS1 knockdown inhibited cell proliferation, migration, and invasion in U2OS and MG63 cells, while upregulation had the opposite effects in vitro. Moreover, FEZF1-AS1 depletion inhibited tumor growth and metastasis in vivo. We found that FEZF1-AS1 sponged miR-4443 to promote NUPR1 expression in U2OS and MG63 cells. Furthermore, knockdown of miR-4443 abrogated FEZF1-AS1 silencing-induced inhibition of cell proliferation, migration, and invasion in osteosarcoma. Finally, we found that restoration of NUPR1 rescued the proliferation, migration, and invasion abilities of FEZF1-AS1-depleted U2OS and MG63 cells. Our study indicated that FEZF1-AS1 could promote osteosarcoma progression by sponging miR-4443 to promote NUPR1 expression. The FEZF1-AS1/miR-4443/NUPR1 axis may act as a novel therapeutic strategy for osteosarcoma treatment.

scholarly journals Knockdown long noncoding RNA SLC8A1-AS1 attenuate cell invasion and migration in glioma via suppression of Wnt-β catenin signaling pathways

2020 ◽  
Author(s):  
Ling He ◽  
Hui Yang ◽  
Xiao-long Zhu ◽  
Yan Zhang ◽  
Kun Lv
Keyword(s):  
Noncoding Rna ◽  
Epithelial To Mesenchymal Transition ◽  
Glioma Cells ◽  
Neural System ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Validation Experiment

Abstract Background Glioma, as the most common aggressive malignant tumor in the central nervous system, is still an insurmountable disease in neural system. The potential mechanism of its carcinogenesis remains largely unclear. Methods In the present study, we identified dysregulated lncRNA solute carrier family 8 member A1 antisense RNA 1 (SLC8A1-AS1) as associated with glioma based on The Cancer Genome Atlas (TCGA)data. Validation experiment was conducted to confirm a high expression level of lncRNA SLC8A1-AS1 in glioma tissues. Results Down-regulation of lncRNA SLC8A1-AS1 suppressed proliferation, clone formation, migration and invasion of glioma cells in vitro and in vivo. Moreover, lncRNA SLC8A1-AS1 silencing decreased the activity of the Wnt/β-catenin pathway and suppressed the epithelial to mesenchymal transition (EMT) in glioma cells. Conclusions Collectively, these findings provide a novel insights into the function and mechanism of lncRNA SLC8A1-AS1 in the pathogenesis of glioma and highlight its potential as a therapeutic target for glioma intervention.

scholarly journals JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chao Jing ◽  
Dandan Liu ◽  
Qingchuan Lai ◽  
Linqi Li ◽  
Mengqian Zhou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Gene Expression Omnibus ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
In Vivo Experiments

Abstract Background Deubiquitinating enzymes (DUBs) play critical roles in various cancers by modulating functional proteins post-translationally. Previous studies have demonstrated that DUB Josephin Domain Containing 1 (JOSD1) is implicated in tumor progression, however, the role and mechanism of JOSD1 in head and neck squamous cell carcinoma (HNSCC) remain to be explored. In this study, we aimed to identify the clinical significance and function of JOSD1 in HNSCC. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to find novel DUBs in HNSCC. Immunohistochemistry assay was performed to determine the expression of JOSD1 in our cohort of 42 patients suffered with HNSCC. Kaplan–Meier analysis was used to identify the correlation between JOSD1 and the prognosis of HNSCC patients. The regulation of BRD4 on JOSD1 was determined by using pharmacological inhibition and gene depletion. The in vitro and in vivo experiments were conducted to elucidate the role of JOSD1 in HNSCC. Results The results of IHC showed that JOSD1 was aberrantly expressed in HNSCC specimens, especially in the chemoresistant ones. The overexpression of JOSD1 indicated poor clinical outcome of HNSCC patients. Moreover, JOSD1 depletion dramatically impaired cell proliferation and colony formation, and promoted cisplatin-induced apoptosis of HNSCC cells in vitro. Additionally, JOSD1 suppression inhibited the tumor growth and improved chemosensitivity in vivo. The epigenetic regulator BRD4 contributed to the upregulation of JOSD1 in HNSCC. Conclusions These results demonstrate that JOSD1 functions as an oncogene in HNSCC progression, and provide a promising target for clinical diagnosis and therapy of HNSCC.

scholarly journals LINC00958 promotes the proliferation of TSCC via miR-211-5p/CENPK axis and activating the JAK/STAT3 signaling pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bo Jia ◽  
Junfeng Dao ◽  
Jiusong Han ◽  
Zhijie Huang ◽  
Xiang Sun ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Xenograft Model ◽  
Tumor Xenograft ◽  
Luciferase Reporter ◽  
Cell Cycle Regulators ◽  
Normal Tissues ◽  
Stat3 Signaling ◽  
Long Intergenic Noncoding Rna

Abstract Background Tongue squamous cell carcinoma (TSCC) is one of the most common oral tumors. Recently, long intergenic noncoding RNA 00958 (LINC00958) has been identified as an oncogene in human cancers. Nevertheless, the role of LINC00958 and its downstream mechanisms in TSCC is still unknown. Methods The effect of LINC00958 on TSCC cells proliferation and growth were assessed by CCK-8, colony formation, 5-Ethynyl-2′-deoxyuridline (EdU) assay and flow cytometry assays in vitro and tumor xenograft model in vivo. Bioinformatics analysis was used to predict the target of LINC00958 in TSCC, which was verified by RNA immunoprecipitation and luciferase reporter assays. Results LINC00958 was increased in TSCC tissues, and patients with high LINC00958 expression had a shorter overall survival. LINC00958 knockdown significantly decreased the growth rate of TSCC cells both in vitro and in vivo. In mechanism, LINC00958 acted as a ceRNA by competitively sponging miR-211-5p. In addition, we identified CENPK as a direct target gene of miR-211-5p, which was higher in TSCC tissues than that in adjacent normal tissues. Up-regulated miR-211-5p or down-regulated CENPK could abolish LINC00958-induced proliferation promotion in TSCC cells. Furthermore, The overexpression of CENPK promoted the expression of oncogenic cell cycle regulators and activated the JAK/STAT3 signaling. Conclusions Our findings suggested that LINC00958 is a potential prognostic biomarker in TSCC.

scholarly journals PRKAR1B-AS2 Long Noncoding RNA Promotes Tumorigenesis, Survival, and Chemoresistance via the PI3K/AKT/mTOR Pathway

2021 ◽  
Vol 22 (4) ◽  
pp. 1882
Author(s):  
Abdelrahman M. Elsayed ◽  
Emine Bayraktar ◽  
Paola Amero ◽  
Salama A. Salama ◽  
Abdelaziz H. Abdelaziz ◽  
...  
Keyword(s):  
Mouse Model ◽  
Long Noncoding Rna ◽  
Proteomic Analysis ◽  
Noncoding Rna ◽  
Mtor Pathway ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Physical Interaction ◽  
Cisplatin Sensitivity

Many long noncoding RNAs have been implicated in tumorigenesis and chemoresistance; however, the underlying mechanisms are not well understood. We investigated the role of PRKAR1B-AS2 long noncoding RNA in ovarian cancer (OC) and chemoresistance and identified potential downstream molecular circuitry underlying its action. Analysis of The Cancer Genome Atlas OC dataset, in vitro experiments, proteomic analysis, and a xenograft OC mouse model were implemented. Our findings indicated that overexpression of PRKAR1B-AS2 is negatively correlated with overall survival in OC patients. Furthermore, PRKAR1B-AS2 knockdown-attenuated proliferation, migration, and invasion of OC cells and ameliorated cisplatin and alpelisib resistance in vitro. In proteomic analysis, silencing PRKAR1B-AS2 markedly inhibited protein expression of PI3K-110α and abrogated the phosphorylation of PDK1, AKT, and mTOR, with no significant effect on PTEN. The RNA immunoprecipitation detected a physical interaction between PRKAR1B-AS2 and PI3K-110α. Moreover, PRKAR1B-AS2 knockdown by systemic administration of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine nanoparticles loaded with PRKAR1B-AS2–specific small interfering RNA enhanced cisplatin sensitivity in a xenograft OC mouse model. In conclusion, PRKAR1B-AS2 promotes tumor growth and confers chemoresistance by modulating the PI3K/AKT/mTOR pathway. Thus, targeting PRKAR1B-AS2 may represent a novel therapeutic approach for the treatment of OC patients.

scholarly journals Potential Role of microRNA-183 as a Tumor Suppressor in Hepatocellular Carcinoma

2018 ◽  
Vol 51 (5) ◽  
pp. 2065-2072 ◽  
Author(s):  
Wei Bian ◽  
Hongfei Zhang ◽  
Miao Tang ◽  
Shaojun Zhang ◽  
Lichao Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Metastatic Progression ◽  
Mesenchymal Transition ◽  
Reporter Assays

Background/Aims: Disseminated tumors, known as metastases, are responsible for ninety-percent of mortality due to cancer. Epithelial to mesenchymal transition, a phenomenon required for morphological conversion of non-motile discoid shaped epithelial cells to highly motile spindle-shaped mesenchymal cells, is thought to be a pre-requisite for metastatic progression. Metastasis-associated 1 (MTA1) protein is a prime inducer of EMT and metastatic progression in all solid tumors including hepatocellular carcinoma (HCC). However, the molecular mechanisms that regulate the expression and function of MTA1 in HCC have not been elucidated. Methods: In silico prediction algorithms were used to find microRNAs (miRNAs) that may target MTA1. We examined the relationship between the expression of MTA1 and miR-183 using quantitative real time PCR. We also determined the levels of the MTA1 protein using immunohistochemistry. Reporter assays, in the presence and absence of the miR-183 mimic, were used to confirm MTA1 as a bona fide target of miR183. The effect of miR-183 on HCC pathogenesis was determined using a combination of in vitro migration and invasion assay, together with in vivo xenograft experiments. The correlation between miR-183 and MTA1 expression was also studied in samples from HCC patients, and in The Cancer Genome Atlas dataset. Results: Analysis of the sequence database revealed that MTA1 is a putative target of miR-183. MTA1 protein and RNA expression showed opposite trends to miR-183 expression in breast, renal, prostate, and testicular tissue samples from cancer patients, and in the metastatic HCC cell line HepG2. An inverse correlation was also observed between MTA1 (high) and miR-183 (low) expression within samples from HHC patients and in the TCGA dataset. Reporter assays in HepG2 cells showed that miR-183 could inhibit translation of a reporter harboring the wild-type, but not the mutant miR-183 3’-untranslated region (UTR). In addition, miR-183 significantly inhibited in vitro migration and invasion in HepG2 cells, and in vivo hepatic metastasis. Conclusion: Our results reveal a novel post-transcriptional regulatory mechanism for MTA1 expression via miR-183, which is suppressed during HCC pathogenesis.

scholarly journals lncRNA NORAD Contributes to Colorectal Cancer Progression by Inhibition of miR-202-5p

2018 ◽  
Vol 26 (9) ◽  
pp. 1411-1418 ◽  
Author(s):  
Jie Zhang ◽  
Xiao-Yan Li ◽  
Ping Hu ◽  
Yuan-Sheng Ding
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Cancer Metastasis ◽  
Cellular Proliferation ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Competing Endogenous Rna

Previous study indicates that long noncoding RNA NORAD could serve as a competing endogenous RNA to pancreatic cancer metastasis. However, its role in colorectal cancer (CRC) needs to be investigated. In the present study, we found that the expression of NORAD was significantly upregulated in CRC tissues. Furthermore, the expression of NORAD was positively related with CRC metastasis and patients’ poor prognosis. Knockdown of NORAD markedly inhibited CRC cell proliferation, migration, and invasion but induced cell apoptosis in vitro. In vivo experiments also indicated an inhibitory effect of NORAD on tumor growth. Mechanistically, we found that NORAD served as a competing endogenous RNA for miR-202-5p. We found that there was an inverse relationship between the expression of NORAD and miR-202-5p in CRC tissues. Moreover, overexpression of miR-202-5p in SW480 and HCT116 cells significantly inhibited cellular proliferation, migration, and invasion. Taken together, our study demonstrated that the NORAD/miR-202-5p axis plays a pivotal function on CRC progression.

scholarly journals Curcumol inhibits malignant biological behaviors and TMZ-resistance of glioma cells via reducing long noncoding RNA FoxD2-As1 promoted EZH2 activation

2021 ◽  
Author(s):  
Xuyang Lv ◽  
Jiangchuan Sun ◽  
Linfeng Hu ◽  
Ying Qian ◽  
Chunlei Fan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Noncoding Rna ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Self Renewal

Abstract Background: Although curcumol has been shown to possess antitumor effects in several cancers, its effects on glioma are largely unknown. Recently, lncRNAs have been reported to play an oncogenic role through epigenetic modifications. Therefore, here, we investigated whether curcumol inhibited glioma progression by reducing FOXD2-AS1-mediated enhancer of zeste homolog 2 (EZH2) activation.Methods: MTT, colony formation, flow cytometry, Transwell, and neurosphere formation assays were used to assess cell proliferation, cell cycle, apoptosis, the percentage of CD133+ cells, the migration and invasion abilities, and the self-renewal ability. qRT-PCR, western blotting, immunofluorescence, and immunohistochemical staining were used to detect mRNA and protein levels. Isobologram analysis and methylation-specific PCR were used to analyze the effects of curcumol on TMZ resistance in glioma cells. DNA pull-down and Chip assays were employed to explore the molecular mechanism underlying the functions of curcumol in glioma cells. Tumorigenicity was determined using a xenograft formation assay. Results: Curcumol inhibited the proliferation, metastasis, self-renewal ability, and TMZ resistance of glioma cells in vitro and in vivo. FOXD2-AS1 was highly expressed in glioma cell lines, and its expression was suppressed by curcumol treatment in a dose- and time-dependent manner. The forced expression of FOXD2-AS1 abrogated the effect of curcumol on glioma cell proliferation, metastasis, self-renewal ability, and TMZ resistance. Moreover, the forced expression of FOXD2-AS1 reversed the inhibitory effect of curcumol on EZH2 activation.Conclusions: We showed for the first time that curcumol is effective in inhibiting malignant biological behaviors and TMZ-resistance of glioma cells by suppressing FOXD2-AS1-mediated EZH2 activation on anti-oncogenes. Our findings offer the possibility of exploiting curcumol as a promising therapeutic agent for glioma treatment and may provide an option for the clinical application of this natural herbal medicine.

scholarly journals LINC00958 promotes the proliferation of TSCC via miR-211-5p/CENPK axis and activating the JAK/STAT3 signaling pathway

2021 ◽  
Author(s):  
Bo Jia ◽  
Junfeng Dao ◽  
Jiusong Han ◽  
Zhijie Huang ◽  
Xiang Sun ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Xenograft Model ◽  
Tumor Xenograft ◽  
Luciferase Reporter ◽  
Cell Cycle Regulators ◽  
Normal Tissues ◽  
Stat3 Signaling ◽  
Long Intergenic Noncoding Rna

Abstract ​ Background: Tongue squamous cell carcinoma (TSCC) is one of the most common oral tumors. Recently, long intergenic noncoding RNA 00958 (LINC00958) has been identified as an oncogene in human cancers. Nevertheless, the role of LINC00958 and its downstream mechanisms in TSCC is still unknown. Methods: The expression levels of LINC00958 in human TSCC tissues and adjacent normal tissues were detected. The effect of LINC00958 on TSCC cells proliferation and growth were assessed by CCK-8, colony formation, 5-Ethynyl-2’-deoxyuridline (EdU) assay, and flow cytometry assays in vitro and tumor xenograft model in vivo. Bioinformatics analysis was used to predict the target of LINC00958 in TSCC, which was verified by RNA immunoprecipitation and luciferase reporter assays. Results: We found LINC00958 was increased in TSCC tissues, and patients with high LINC00958 expression had a shorter overall survival. LINC00958 knockdown significantly decreased the growth rate of TSCC cells both in vitro and in vivo . In mechanism, LINC00958 acted as a competing endogenous RNA (ceRNA) by competitively sponging miR-211-5p. In addition, we identified centromere protein K (CENPK) as a direct target gene of miR-211-5p, which was higher in TSCC tissues than that in adjacent normal tissues. Up-regulated miR-211-5p or down-regulated CENPK could abolish LINC00958-induced proliferation promotion in TSCC cells. Conclusion: Furthermore, CENPK promoted the expression of oncogenic cell cycle regulators and activated the JAK/STAT3 signaling. Our findings suggest that LINC00958 is a potential prognostic biomarker in TSCC.

Sign in / Sign up

Export Citation Format

Share Document