scholarly journals Long Non-Coding RNA HOXA-AS2 Regulates Malignant Glioma Behaviors and Vasculogenic Mimicry Formation via the MiR-373/EGFR Axis

2017 ◽  
Vol 45 (1) ◽  
pp. 131-147 ◽  
Author(s):  
Yana Gao ◽  
Hai Yu ◽  
Yunhui Liu ◽  
Xiaobai Liu ◽  
Jian Zheng ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Cell Viability ◽  
Malignant Glioma ◽  
Cell Lines ◽  
Vasculogenic Mimicry ◽  
Tube Formation ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Expression And Activity

Background/Aims: Vasculogenic mimicry (VM) has been reported to be a novel glioma neovascularization process. Anti-VM therapy provides new insight into glioma clinical management. In this study, we revealed the role of the long non-coding RNA HOXA cluster antisense RNA 2 (HOXA-AS2) in malignant glioma behaviors and VM formation. Methods: Quantitative real-time PCR was performed to determine the expression levels of HOXA-AS2 in glioma samples and glioblastoma cell lines. CD34-periodic acid-Schiff dual-staining was performed to assess VM in glioma samples. CCK-8, transwell, and Matrigel tube formation assays were performed to measure the effects of HOXA-AS2 knockdown on cell viability, migration, invasion, and VM tube formation, respectively. RNA immunoprecipitation, dual-luciferase reporter and Western blot assays were performed to explore the molecular mechanisms underlying the functions of HOXS-AS2 in glioblastoma cells. A nude mouse xenograft model was used to investigate the role of HOXA-AS2 in xenograft glioma growth and VM density. Student’s t-tests, one-way ANOVAs followed by Bonferroni posthoc tests, and chi-square tests were used for the statistical analyses. Results: HOXA-AS2 was upregulated in glioma samples and cell lines and was positively correlated with VM. HOXA-AS2 knockdown attenuated cell viability, migration, invasion, and VM formation in glioma cells and inhibited the expression of vascular endothelial-cadherin (VE-cadherin), as well as the expression and activity of matrix metalloproteinase matrix metalloproteinase (MMP)-2 and MMP-9. miR-373 was downregulated in glioma samples and cell lines and suppressed malignancy in glioblastoma cells. HOXA-AS2 bound to miR-373 and negatively regulated its expression. Epidermal growth factor receptor (EGFR), a target of miR-373, increased the expression levels of VE-cadherin, as well as the expression and activity levels of MMP-2 and MMP-9, via activating phosphatidylinositol 3-kinase/serine/threonine kinase pathways. HOXA-AS2 knockdown combined with miR-373 overexpression yielded optimal tumor suppressive effects and the lowest VM density in vivo. Conclusion: HOXA-AS2 knockdown inhibited malignant glioma behaviors and VM formation via the miR-373/EGFR axis.

scholarly journals The Biological and Clinical Role of the Long Non-Coding RNA LOC642852 in Ovarian Carcinoma

2020 ◽  
Vol 21 (15) ◽  
pp. 5237 ◽  
Author(s):  
Natalie Filippov-Levy ◽  
Reuven Reich ◽  
Ben Davidson
Keyword(s):  
Matrix Metalloproteinase ◽  
Cell Signaling ◽  
Ovarian Carcinoma ◽  
Serous Carcinoma ◽  
Spheroid Formation ◽  
Clinical Role ◽  
Cerna Network ◽  
Non Coding Rna ◽  
Long Non Coding Rna

The objective of the present study was to analyze the biological and clinical role of the long non-coding RNA LOC642852 in ovarian carcinoma (OC). LOC642852 expression was analyzed in seven OC cell lines (OVCAR-3, OVCAR-8, OVCA 433, OVCA 429, OC 238, DOV13, ES-2) and 139 high-grade serous carcinoma (HGSC) specimens (85 effusions, 54 surgical specimens). Following LOC642852 knockout (KO) using the CRISPR/Cas9 system, OVCAR-8 HGSC cells were analyzed for spheroid formation, migration, invasion, proliferation, matrix metalloproteinase (MMP) activity, and expression of cell signaling proteins. OVCAR-8 cells with LOC642852 KO were significantly less motile and less invasive compared to controls, with no differences in spheroid formation, proliferation, or matrix metalloproteinase (MMP) activity. Total Akt and Erk levels were comparable in controls and KO cells, but their phosphorylation was significantly increased in the latter. In clinical specimens, LOC642852 was overexpressed in ovarian tumors and omental/peritoneal metastases compared to effusion specimens (p = 0.013). A non-significant trend for shorter overall (p = 0.109) and progression-free (p = 0.056) survival was observed in patients with HGSC effusions with high LOC642852 levels. Bioinformatics analysis showed potential roles for LOC642852 as part of the TLE3/miR-221-3p ceRNA network and in relation to the FGFR3 protein. In conclusion, LOC642852 inactivation via CRISPR/Cas9 affects cell signaling, motility, and invasion in HGSC cells. LOC642852 is differentially expressed in HGSC cells at different anatomical sites. Its potential role in regulating the TLE3/miR-221-3p ceRNA network and FGFR3 merits further research.

scholarly journals SP1 induced Long non-coding RNA AGAP2-AS1 promotes cholangiocarcinoma proliferation via silencing of CDKN1A 

2020 ◽  
Author(s):  
Hao Ji ◽  
Juan Wang ◽  
Binbin Lu ◽  
Juan Li ◽  
Jing Zhou ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Molecular Mechanism ◽  
Cell Lines ◽  
Mrna Degradation ◽  
Biological Role ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Regulate Gene

Abstract Background: LncRNA can regulate gene at various levels such as apparent genetics, alternative splicing, and regulation of mRNA degradation. However, the molecular mechanism of LncRNA in cholangiocarcinoma is still unclear. This deserves further exploration. Methods:We investigated the expression of AGAP2-AS1 in 32 CCA tissues and two CCA cell lines. We found a LncRNA AGAP2-AS1 which induced by SP1 has not been reported in CCA, and Knockdown and overexpression were used to investigate the biological role of AGAP2-AS1 in vitro. CHIP and RIP were performed to verify the putative targets of AGAP2-AS1. Results:AGAP2-AS1 was significantly upregulated in CCA tumor tissues.SP1 induced AGAP2-AS1 plays an important role in tumorigenesis. AGAP2-AS1 knockdown significantly inhibited proliferation and caused apoptosis in CCA cells. In addition, we demonstrated that AGAP2-AS1 promotes the proliferation of CCA. Conclusions: We conclude that the long non-coding RNA AGAP2-AS1 plays a role in promoting the proliferation of cholangiocarcinoma.

scholarly journals Long Non-Coding RNA MALAT1 Decreases the Sensitivity of Resistant Glioblastoma Cell Lines to Temozolomide

2017 ◽  
Vol 42 (3) ◽  
pp. 1192-1201 ◽  
Author(s):  
Hongwei Li ◽  
Xiaoli Yuan ◽  
Dongming Yan ◽  
Dongpeng Li ◽  
Fangxia Guan ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Viability ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Biology ◽  
Glioblastoma Cell ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Glioblastoma Cell Lines

Background/Aim: Multidrug resistance (MDR) is largely responsible for the failure of chemotherapy. The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript (MALAT1) has been reported to be closely related to tumor biology. In the present study, whether MALAT1 contributes to the resistance of glioblastoma cell lines to temozolomide (TMZ) was investigated. Methods: The glioblastoma cell lines U251 and U87 were exposed to increasing concentrations of TMZ to generate TMZ-resistant colonies (the U251/TMZ and U87/TMZ cell lines). The expression levels of MALAT1 and proteins related to epithelial-mesenchymal transition (EMT) were detected by real-time PCR and western blot, respectively. After the transfection of si-MALAT1 or pcDNA-MALAT1, cell viability, mRNA expression of MDR-associated proteins (MDR1, MRP5 and LRP1), and protein expression of EMT related proteins (ZEB1, Snail and SLUG) were evaluated. Results: The expression of MALAT1 was upregulated in the U251/TMZ and U87/TMZ cell lines compared to that in U251 and U87 cell lines, respectively. The treatment of si-MALAT1 decreased MDR1, MRP5, and LRP1 expression, enhanced cell sensitivity to TMZ, and downregulated ZEB1 protein expression, whereas pcDNA-MALAT1 had the opposite effects. However, the effects of si-MALAT1 on MDR -associated protein expression, cell viability, and EMT status were reversed by the transfection of pcDNA-ZEB1, and the effects of pcDNA-MALAT1 were reversed by the transfection of si-ZEB1. In vivo, MALAT1 overexpression enhanced tumors’ TMZ resistance and upregulated ZEB1 expression. Conclusion: MALAT1 decreased the sensitivity of resistant glioma cell lines to TMZ by regulating ZEB1.

scholarly journals The Long Non-Coding RNA Prader Willi/Angelman Region RNA5 (PAR5) Is Downregulated in Anaplastic Thyroid Carcinomas Where It Acts as a Tumor Suppressor by Reducing EZH2 Activity

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 235 ◽  
Author(s):  
Simona Pellecchia ◽  
Romina Sepe ◽  
Myriam Decaussin-Petrucci ◽  
Cristina Ivan ◽  
Masayoshi Shimizu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Cancer Progression ◽  
P Value ◽  
Thyroid Carcinomas ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
E Cadherin

Anaplastic thyroid carcinoma (ATC) represents one the most aggressive neoplasias in humans, and, nowadays, limited advances have been made to extend the survival and reduce the mortality of ATC. Thus, the identification of molecular mechanism underlying its progression is needed. Here, we evaluated the long non-coding RNA (lncRNA) expression profile of nine ATC in comparison with five normal thyroid tissues by a lncRNA microarray. By this analysis, we identified 19 upregulated and 28 downregulated lncRNAs with a fold change >1.1 or <−1.1 and p-value < 0.05, in ATC samples. Some of them were subsequently validated by qRT-PCR. Then, we investigated the role of the lncRNA Prader Willi/Angelman region RNA5 (PAR5), drastically and specifically downregulated in ATC. The restoration of PAR5 reduces proliferation and migration rates of ATC-derived cell lines indicating that its downregulation contributes to thyroid cancer progression. Our results suggest that PAR5 exerts its anti-oncogenic role by impairing Enhancer of Zeste Homolog 2 (EZH2) oncogenic activity since we demonstrated that PAR5 interacts with it in thyroid cancer cell lines, reducing EZH2 protein levels and its binding on the E-cadherin promoter, relieving E-cadherin from the negative regulation by EZH2. Consistently, EZH2 is overexpressed in ATC, but not in differentiated thyroid carcinomas. The results reported here define a tumor suppressor role for PAR5 in undifferentiated thyroid neoplasias, further highlighting the pivotal role of lncRNAs in thyroid carcinogenesis.

scholarly journals Long non-coding RNA NEAT1 promotes hepatocellular carcinoma cell proliferation through the regulation of miR-129-5p-VCP-IκB

2017 ◽  
Vol 313 (2) ◽  
pp. G150-G156 ◽  
Author(s):  
Luo Fang ◽  
Jiao Sun ◽  
Zongfu Pan ◽  
Yu Song ◽  
Like Zhong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Cell Viability ◽  
Cell Lines ◽  
Target Genes ◽  
Regulatory Mechanism ◽  
Huh7 Cell ◽  
Non Coding Rna ◽  
Target Molecules ◽  
Long Non Coding Rna

Long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) plays an important role in the pathogenesis and development of several types of cancer. However, the functional mechanism of NEAT1 in hepatocellular carcinoma (HCC) remains unclear. NEAT1 and microRNA (miR)-129-5p expression in HCC tissues and cell lines was quantified by means of quantitative PCR. The effects of NEAT1 expression inhibition or upregulation in HCC cell lines were analyzed in terms of cell viability and apoptosis. Biological software was used to predict the binding sites of NEAT1 and miR-129-5p. The expression of the miR-129-5p target molecules valosin-containing protein (VCP) and IκB was detected using Western blotting. The effect of NEAT1 on tumor growth was observed in mouse models of transplanted hepatoma. In the present study, it was concluded that the expression of NEAT1 was significantly increased in the HCC tissues and cell lines. Meanwhile, after downregulating NEAT1 expression in HepG2/Huh7 cell lines, the cell viability was significantly lowered, whereas the corresponding rate of apoptosis was significantly increased. Additionally, it was found that the NEAT1 and miR-129-5p expression showed a negative correlation in HCC tissues. It was further proved that there was a certain negative regulatory mechanism between NEAT1 and miR-129-5p, which was related to the expression of VCP and IκB. The mouse model experiments confirmed that the interference with NEAT1 expression inhibited tumor growth. The study concluded that the overexpression of NEAT1 inhibited the expression of miR-129-5p by regulating VCP/IκB, thereby promoting the proliferation of HCC cells. This study provides new insights into the pathogenesis of HCC, as well as identifying new target genes for diagnosis and treatment. NEW & NOTEWORTHY The results provide strong evidence that upregulated NEAT1 promotes the proliferation of cancer cells in hepatocellular carcinoma (HCC) and this regulatory mechanism depends on the microRNA (miR)-129-5p-valosin-containing protein-IκB axis. The study also indicates that NEAT1 could be a potential therapeutic target for HCC.

scholarly journals Sp1 Induced Long Non-coding Rna Agap2-as1 Promotes Cholangiocarcinoma Proliferation via Silencing of Cdkn1a

2020 ◽  
Author(s):  
Hao Ji ◽  
Juan Wang ◽  
Binbin Lu ◽  
Juan Li ◽  
Jing Zhou ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Molecular Mechanism ◽  
Cell Lines ◽  
Biological Role ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Regulate Gene

Abstract Background: LncRNA can regulate gene at various levels such as apparent genetics, alternative splicing, and regulation of mRNA degradation.However, the molecular mechanism of LncRNA in cholangiocarcinoma is still unclear.This deserves further exploration.Methods: We investigated the expression of AGAP2-AS1 in 32 CCA tissues and two CCA cell lines. We found a LncRNA AGAP2-AS1 which induced by SP1 has not been reported in cholangiocarcinoma and studied itKnockdown and overexpression were used to investigate the biological role of AGAP2-AS1 in vitro. CHIP and RIP were performed to verify the putative targets of AGAP2-AS1.Results: AGAP2-AS1 was significantly upregulated in 32 CCA tumor tissues.SP1 induced AGAP2-AS1 plays an important role in tumorigenesis.AGAP2-AS1 knockdown significantly inhibited proliferation and caused apoptosis in CCA cells. In addition, we demonstrated that AGAP2-AS1 acts as an oncogene in CCA.Conclusions: We conclude that the long non-coding RNA AGAP2-AS1 plays a role in promoting the proliferation of cholangiocarcinoma.

snoRNA23 enhances the progression of hepatocellular carcinoma via regulation of the Wnt/?-catenin pathway

2021 ◽  
Vol 67 (2) ◽  
pp. 155-160
Author(s):  
Shengxian Qiao ◽  
Xu Zhang ◽  
Zhichao Wu ◽  
Lei Zhang ◽  
Shaojie Sun
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Viability ◽  
Colony Formation ◽  
Lymphatic Vessel ◽  
Tube Formation ◽  
Ductal Adenocarcinoma ◽  
Vessel Formation ◽  
Non Coding Rna ◽  
Hcc Cells

Small nucleolar non-coding RNA(snoRA)23 is upregulated in human pancreatic ductal adenocarcinoma. However, to the best of our knowledge, the role of snoRA23 in hepatocellular carcinoma progression has not been determined. MTT and colony formation assays were used to assess the cell viability and proliferation of HCC cells with snoRA23 knocked down, respectively, and a lymphatic vessel formation assay was used to determine tube formation ability of Human dermal lymphatic endothelial cells treated with conditioned media from HCC cell cultures. The results showed that snoRA23 knockdown attenuated cell viability, colony formation,and lymphatic vessel formation in HCC cells. snoRA23 was correlated with the prolonged overall survival of patients with HCC. Additionally, snoRA23 knockdown downregulated the Wnt/?-catenin signaling pathway by decreasing Wnt3a expression and ?-catenin levels.?-methylacyl-CoA racemase (AMACR) levels were notably decreased by snoRA23 depletion. Finally, it was confirmed that AMACR overexpression partially rescued snoRA23-modulated HCC tumorigenesis. The results of the present study provide further insight into the role of non-coding RNAs in the development and progression of HCC.

scholarly journals Non-coding RNA Activated by DNA Damage: Review of Its Roles in the Carcinogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Soudeh Ghafouri-Fard ◽  
Tahereh Azimi ◽  
Bashdar Mahmud Hussen ◽  
Atefe Abak ◽  
Mohammad Taheri ◽  
...  
Keyword(s):  
Dna Damage ◽  
Clinical Outcome ◽  
Cell Lines ◽  
Genome Integrity ◽  
Akt Pathway ◽  
Poor Clinical Outcome ◽  
Over Expression ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Long intergenic non-coding RNA 00657 (LINC00657) or “non-coding RNA activated by DNA damage” (NORAD) is an extremely conserved and copious long non-coding RNA (lncRNA). This transcript has pivotal role in the preservation of genome integrity. Several researches have appraised the role of NORAD in the evolution of human cancers with most of them indicating an oncogenic role for this lncRNA. Several miRNAs such as miR-199a-3p, miR-608, miR−155−5p, miR-590-3p, miR-495-3p, miR-608, miR-202-5p, miR-125a-3p, miR-144-3p, miR−202−5p, and miR-30a-5p have been recognized as targets of NORAD in different cancer cell lines. In addition, NORAD has interactions with cancer-related pathways, particularly STAT, TGF-β, Akt/mTOR, and PI3K/AKT pathway. Over-expression of NORAD has been related with poor clinical outcome of patients with diverse types of neoplasms. Collectively, NORAD is a prospective marker and target for combating cancer.

scholarly journals Long Non-Coding RNA MALAT1 Protects Human Osteoblasts from Dexamethasone-Induced Injury via Activation of PPM1E-AMPK Signaling

2018 ◽  
Vol 51 (1) ◽  
pp. 31-45 ◽  
Author(s):  
Jian-bo Fan ◽  
Yingzi Zhang ◽  
Wei Liu ◽  
Xin-hui Zhu ◽  
Da-wei Xu ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Osteoblastic Cells ◽  
Blue Staining ◽  
Osteoblastic Cell ◽  
Human Osteoblasts ◽  
Ampk Signaling ◽  
Non Coding Rna ◽  
Primary Human Osteoblasts ◽  
Long Non Coding Rna

Background/Aims: Dexamethasone (Dex) induces injuries to human osteoblasts. In this study, we tested the potential role of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) in this process. Materials: Two established human osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts were treated with Dex. Lnc-MALAT1 expression was analyzed by quantitative real-time polymerase chain reaction assay. Cell viability, apoptosis, and death were tested by the MTT assay, histone-DNA assay, and trypan blue staining assay, respectively. AMP-activated protein kinase (AMPK) signaling was evaluated by western blotting and AMPK activity assay. Results: Lnc-MALAT1 expression was downregulated by Dex treatment in the established osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts. The level of Lnc-MALAT1 was decreased in the necrotic femoral head tissues of Dex-administered patients. In osteoblastic cells and primary human osteoblasts, forced overexpression of Lnc-MALAT1 using a lentiviral vector (LV-MALAT1) inhibited Dex-induced cell viability reduction, cell death, and apoptosis. Conversely, transfection with Lnc-MALAT1 small interfering RNA aggravated Dex-induced cytotoxicity. Transfection with LV-MALAT1 downregulated Ppm1e (protein phosphatase, Mg2+/ Mn2+-dependent 1e) expression to activate AMPK signaling. Treatment of osteoblasts with AMPKα1 short hairpin RNA or dominant negative mutation (T172A) abolished LV-MALAT1-induced protection against Dex-induced cytotoxicity. Furthermore, LV-MALAT1 induced an increase in nicotinamide adenine dinucleotide phosphate activity and activation of Nrf2 signaling. Dex-induced reactive oxygen species production was significantly attenuated by LV-MALAT1 transfection in osteoblastic cells and primary osteoblasts. Conclusion: Lnc-MALAT1 protects human osteoblasts from Dex-induced injuries, possibly via activation of Ppm1e-AMPK signaling.

scholarly journals SP1 induced long non-coding RNA AGAP2-AS1 promotes cholangiocarcinoma proliferation via silencing of CDKN1A

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Hao Ji ◽  
Juan Wang ◽  
Binbin Lu ◽  
Juan Li ◽  
Jing Zhou ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Molecular Mechanism ◽  
Cell Lines ◽  
Mrna Degradation ◽  
Non Coding Rna ◽  
Tumor Tissues ◽  
Long Non Coding Rna ◽  
Regulate Gene

Abstract Background LncRNA can regulate gene at various levels such as apparent genetics, alternative splicing, and regulation of mRNA degradation. However, the molecular mechanism of LncRNA in cholangiocarcinoma is still unclear. This deserves further exploration. Methods We investigated the expression of AGAP2-AS1 in 32 CCA tissues and two CCA cell lines. We found a LncRNA AGAP2-AS1 which induced by SP1 has not been reported in CCA, and Knockdown and overexpression were used to investigate the biological role of AGAP2-AS1 in vitro. CHIP and RIP were performed to verify the putative targets of AGAP2-AS1. Results AGAP2-AS1 was significantly upregulated in CCA tumor tissues. SP1 induced AGAP2-AS1 plays an important role in tumorigenesis. AGAP2-AS1 knockdown significantly inhibited proliferation and caused apoptosis in CCA cells. In addition, we demonstrated that AGAP2-AS1 promotes the proliferation of CCA. Conclusions We conclude that the long non-coding RNA AGAP2-AS1 plays a role in promoting the proliferation of cholangiocarcinoma.

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