scholarly journals Long noncoding RNA TSLNC8 Enhances Pancreatic Cancer Aggressiveness by Regulating CTNNB1 Expression via Association with HuR

2020 ◽  
Author(s):  
Wei Chai ◽  
Ruhai Liu ◽  
Fengshan Li ◽  
Zhiquan Zhang ◽  
Bao Lei
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Cancer Aggressiveness ◽  
Rna Immunoprecipitation ◽  
The Stability ◽  
Proliferation And Invasion

Abstract Background Pancreatic cancer (PC) is one of the most lethal malignancies worldwide. Tumor suppressor long noncoding RNA on chromosome 8p12 (TSLNC8) is a newly identified long noncoding RNA (lncRNA) and play an important role in human cancers. However, the function and molecular mechanism of TSLNC8 in PC progression remains to be elucidated. Methods qRT-PCR was performed to examine the expression pattern of TSLNC8 in PC tissues and cell lines. Overexpression and knockdown experiments were conducted to detect the function of TSLNC8 in PC. The interaction between TSLNC8 and HuR was tested by RNA immunoprecipitation assay. Results Our results showed a significant increase of TSLNC8 expression in PC tissues and cell lines. Upregulation of TSLNC8 expression in PC tissues was closely correlated with TNM stage, distant and lymph node metastasis, and poor prognosis of PC patients. Functional experiments demonstrated that TSLNC8 promoted PC cells proliferation and invasion in vitro, and enhanced PC growth and metastasis in vivo. Mechanistically, TSLNC8 associated with HuR, promoted the binding of HuR with CTNNB1 mRNA and increased the stability of CTNNB1 mRNA, thus activating WNT/β-catenin signaling pathway. Conclusion Our present study revealed that oncogenic lncRNA TSLNC8 positively regulate PC growth and metastasis via HuR-mediated mRNA stability of CTNNB1, extending the understanding of PC pathogenesis regulated by lncRNAs.

scholarly journals Long noncoding RNA TSLNC8 Enhances Pancreatic Cancer Aggressiveness by Regulating CTNNB1 Expression via Association with HuR

2020 ◽  
Author(s):  
Wei Chai ◽  
Ruhai Liu ◽  
Fengshan Li ◽  
Zhiquan Zhang ◽  
Bao Lei
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Cancer Aggressiveness ◽  
Rna Immunoprecipitation ◽  
The Stability ◽  
Proliferation And Invasion

Abstract Background Pancreatic cancer (PC) is one of the most lethal malignancies worldwide. Tumor suppressor long noncoding RNA on chromosome 8p12 (TSLNC8) is a newly identified long noncoding RNA (lncRNA) and play an important role in human cancers. However, the function and molecular mechanism of TSLNC8 in PC progression remains to be elucidated. Methods qRT-PCR was performed to examine the expression pattern of TSLNC8 in PC tissues and cell lines. Overexpression and knockdown experiments were conducted to detect the function of TSLNC8 in PC. The interaction between TSLNC8 and HuR was tested by RNA immunoprecipitation assay. Results Our results showed a significant increase of TSLNC8 expression in PC tissues and cell lines. Upregulation of TSLNC8 expression in PC tissues was closely correlated with TNM stage, distant and lymph node metastasis, and poor prognosis of PC patients. Functional experiments demonstrated that TSLNC8 promoted PC cells proliferation and invasion in vitro, and enhanced PC growth and metastasis in vivo. Mechanistically, TSLNC8 associated with HuR, promoted the binding of HuR with CTNNB1 mRNA and increased the stability of CTNNB1 mRNA, thus activating WNT/β-catenin signaling pathway. Conclusion Our present study revealed that oncogenic lncRNA TSLNC8 positively regulate PC growth and metastasis via HuR-mediated mRNA stability of CTNNB1, extending the understanding of PC pathogenesis regulated by lncRNAs.

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.

Lentivirus-Mediated RNA Interference Targeting the Long Noncoding RNA HOTAIR Inhibits Proliferation and Invasion of Endometrial Carcinoma Cells In Vitro and In Vivo

2014 ◽  
Vol 24 (4) ◽  
pp. 635-642 ◽  
Author(s):  
Jiaming Huang ◽  
Peiqi Ke ◽  
Luyan Guo ◽  
Wei Wang ◽  
Hao Tan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Endometrial Cancer ◽  
Endometrial Carcinoma ◽  
Cancer Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Proliferation And Invasion

ObjectiveThe overexpression of long noncoding RNA HOTAIR is associated with various aggressive solid carcinomas. However, its relationship with endometrial carcinoma has not been reported. The present study aimed to investigate the expression of the long noncoding RNA HOTAIR in endometrial carcinoma, its relationship with the carcinoma’s clinicopathologic features, and the biological function of HOTAIR in regulating endometrial cancer cell proliferation and invasion in vitro and in vivo.MethodsThe expression of HOTAIR was detected in different tissues and cell lines by real-time PCR. Lentivirus-mediated HOTAIR-specific shRNAvectors were transfected into endometrial cancer HEC-1A cells. Cell proliferation and colony formation were examined by CCK-8 assays and colony formation assays, respectively. Invasion and migration were examined by Transwell assays. Flow cytometry assay was used to examine the cell cycle. In addition, xenograft model assays were performed to analyze the growth of endometrial cancer cells in vivo.ResultsOur data showed that HOTAIR expression was higher in endometrial cancer cells and tissues than in normal endometrial tissues. HOTAIR expression was closely related to the tumor stage (P= 0.045), myometrial invasion (P= 0.014), and lymph node metastasis (P= 0.033). The down-regulation of HOTAIR resulted in a significant inhibition of cell proliferation, migration, and invasion and in cell cycle arrest at the G0/G1 phase. Furthermore, HOTAIR depletion significantly suppressed the endometrial cancer tumorigenesis in vivo.ConclusionsThis study is the first to suggest that HOTAIR plays an important role in the carcinogenesis of endometrial cancer. Targeting HOTAIR may be a novel therapeutic strategy for endometrial cancer.

scholarly journals Long Noncoding RNA SNHG1 Regulates LMNB2 Expression by Sponging miR-326 and Promotes Cancer Growth in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Wentao Mu ◽  
Lingyu Guo ◽  
Yang Liu ◽  
Hui Yang ◽  
Shanglei Ning ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Tumor Proliferation ◽  
Nude Mouse Model

ObjectiveThe purpose of the study is to explore the potential competing endogenous RNA (ceRNA) network and investigate the molecular mechanism of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in hepatocellular carcinoma (HCC) development.MethodsBy analyzing the data of HCC in The Cancer Genome Atlas (TCGA) database, we included differentially expressed lncRNA and microRNA (miRNA) profiles and constructed ceRNA networks related to the prognosis of HCC patients. qRT-PCR, Western blotting, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), transwell assay, and the nude mouse model were employed to test the effects of SNHG1 and LMNB2 on tumor proliferation and growth in vitro and in vivo.ResultsIn the study, we identified 115 messenger RNAs (mRNAs), 12 lncRNAs, and 37 miRNAs by intersecting differentially expressed genes (DEGs) in TCGA and StarBase databases. Then, SNHG1–miR-326–LMNB2 pathway came into notice after further survival analysis and hub gene screening. Our results showed that SNHG1 expression was upregulated significantly in HCC tissues and cell lines. Downregulation of both LMNB2, the target of miR-326 in HCC, and SNHG1 inhibited tumor proliferation and growth in vitro and in vivo. Furthermore, SNHG1 could regulate LMNB2 expression through binding to miR-326 in HCC cell lines.ConclusionSNHG1 is a promising prognostic factor in HCC, and the SNHG1–miR-326–LMNB2 axis may be a potential therapeutic target for HCC.

scholarly journals LncRNA HOXD-AS1 functions as a ceRNA to promote hepatocellular carcinoma metastasis in zebrafish xenograft models

2021 ◽  
Author(s):  
Ying Zhang ◽  
Xiaolu Wang ◽  
Feng Qin ◽  
Shaochang Jia
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Noncoding Rna ◽  
Xenograft Model ◽  
Cerna Network ◽  
Xenograft Models ◽  
Proliferation And Invasion ◽  
Hcc Cells

Abstract Background: A few studies have shown that long noncoding RNA (lncRNA) HOXD cluster antisense RNA 1 (HOXD-AS1) plays an important role in hepatocellular carcinoma (HCC) metastasis as a competing endogenous RNA (ceRNA), but there is little in vivo evidence. This study aims to explore the zebrafish HCC xenograft as an in vivo metastasis model to verify the ceRNA network of HOXD-AS1. Methods: The quantitative reverse transcription PCR (qRT-PCR) assay was used to assess the expression level of HOXD-AS1 in HCC cell lines. Knockdown of HOXD-AS1 or miR-130a-3p was performed by transfecting small interfering RNA (siRNA) or microRNA (miRNA) inhibitor, respectively. The proliferation and invasion of HCC cells in vitro were analyzed by CCK-8 and transwell assays. The growth and metastasis of HCC cells in vivo were assessed by zebrafish xenograft models.Results: We verified that HOXD-AS1 was overexpressed in all tested HCC cell lines than the normal hepatic cells. Silence of HOXD-AS1 suppressed cell proliferation and invasion in Hep3B and Huh7 HCC cell lines in vitro. In zebrafish xenograft models, knockdown of HOXD-AS1 also reduced the growth and metastasis of the two HCC cells. Moreover, downregulation of miR-130a-3p not only increased the HCC metastasis, but also rescued the metastasis which inhibited by silence of HOXD-AS1 in vitro and in vivo.Conclusions: Our study demonstrates the metastasis role of the HOXD-AS1/miR-130a-3p ceRNA network in HCC cells in vitro and in vivo, and these findings suggest that zebrafish xenograft model could be used for ceRNA mechanism verification in tumor metastasis.

Long noncoding RNA Linc01296 promotes hepatocellular carcinoma development through regulation of the miR-26a/PTEN axis

2020 ◽  
Vol 401 (3) ◽  
pp. 407-416 ◽  
Author(s):  
Libin Zhang ◽  
Jing Hu ◽  
Menghui Hao ◽  
Liang Bu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Malignant Tumors ◽  
Cell Counting ◽  
Tumor Xenograft ◽  
Migration And Invasion

AbstractLong noncoding RNA 01296 (Lnc01296) is dysregulated in malignant tumors. However, the detailed effect of Linc01296 on hepatocellular carcinoma (HCC) remains largely unknown. In this study, we identified the biological role of Linc01296 in HCC. The levels of Linc01296 in HCC tissues and a panel of cell lines were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of Linc01296 on HCC progression were explored using a Cell Counting Kit-8 (CCK-8), flow cytometry, migration and Transwell invasion assays. The interactions among Linc01296, miR-26a and PTEN were determined using luciferase, RNA immunoprecipitation (RIP) and Western blot assays. Tumor xenograft models were utilized to confirm the in vivo functional roles of Linc01296 in HCC development. Linc01296 expression was increased in both HCC tissue samples and cell lines. Knockdown of Linc01296 suppressed HCC cell processes, such as proliferation, migration and invasion, and enhanced apoptosis in vitro; these effects were reversed by a miR-26a mimic or PTEN overexpression. Furthermore, knockdown of Linc01296 suppressed HCC growth in vivo. These findings indicated that Linc01296 is involved in HCC progression via regulating miR-26a/PTEN.

scholarly journals The role of long noncoding RNA AL161431.1 in the development and progression of pancreatic cancer

2021 ◽  
Author(s):  
Gang Ma ◽  
Guichen Li ◽  
Wufeng Fan ◽  
Yuanhong Xu ◽  
Shaowei Song ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Clinical Samples ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells

Abstract Pancreatic cancer is known for its notorious fast progression and poor prognosis. Long noncoding RNA (lncRNA) AL161431.1 has been reported to be involved in the pathogenesis of different cancers. In this study, we explored the role of lncRNA AL161431.1 in the development and progression of pancreatic cancer by bioinformatic analysis, in vitro and in vivo experiments in pancreatic cancer BxPC-3 and SW1990 cells, as well as clinical samples. We found that lncRNA AL161431.1 was highly expressed in pancreatic cancer cells and tissues. Knock down of lncRNA AL161431.1 led to increased cancer cell death and cell cycle arrest. Xenograft growth of SW1990 cells with stable knockdown of lncRNA AL161431.1 in mice was significantly slower than that of SW1990 cells with scrambled control shRNA. Finally, we showed the involvement of lncRNA AL161431.1 in pancreatic cancer was related to its promotion of epithelial mesenchymal transition process.

scholarly journals The Role of Long Noncoding RNA AL161431.1 in the Development and Progression of Pancreatic Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Gang Ma ◽  
Guichen Li ◽  
Wufeng Fan ◽  
Yuanhong Xu ◽  
Shaowei Song ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Clinical Samples ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells

Pancreatic cancer is known for its notorious fast progression and poor prognosis. Long noncoding RNA (lncRNA) AL161431.1 has been reported to be involved in the pathogenesis of different cancers. In this study, we explored the role of lncRNA AL161431.1 in the development and progression of pancreatic cancer by bioinformatic analysis, in vitro and in vivo experiments in pancreatic cancer BxPC-3 and SW1990 cells, as well as clinical samples. We found that lncRNA AL161431.1 was highly expressed in pancreatic cancer cells and tissues. Knock down of lncRNA AL161431.1 led to increased cancer cell death and cell cycle arrest. Xenograft growth of SW1990 cells with stable knockdown of lncRNA AL161431.1 in mice was significantly slower than that of SW1990 cells with scrambled control shRNA. Finally, we showed the involvement of lncRNA AL161431.1 in pancreatic cancer was related to its promotion of epithelial mesenchymal transition process.

scholarly journals Long noncoding RNA SNHG14 promotes hepatocellular carcinoma progression by regulating miR-876-5p/SSR2 axis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Zhibin Liao ◽  
Hongwei Zhang ◽  
Chen Su ◽  
Furong Liu ◽  
Yachong Liu ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Animal Experiments ◽  
Luciferase Reporter ◽  
Western Blot Assay ◽  
Downstream Target ◽  
Protein Levels ◽  
Elevated Expression ◽  
Rna Immunoprecipitation

Abstract Background Aberrant expressions of long noncoding RNAs (lncRNAs) have been demonstrated to be related to the progress of HCC. The mechanisms that SNHG14 has participated in the development of HCC are obscure. Methods Quantitative real-time PCR (qRT-PCR) was used to measure the lncRNA, microRNA and mRNA expression level. Cell migration, invasion and proliferation ability were evaluated by transwell and CCK8 assays. The ceRNA regulatory mechanism of SNHG14 was evaluated by RNA immunoprecipitation (RIP) and dual luciferase reporter assay. Tumorigenesis mouse model was used to explore the roles of miR-876-5p in vivo. The protein levels of SSR2 were measured by western blot assay. Results In this study, we demonstrated that SNHG14 was highly expressed in HCC tissues, meanwhile, the elevated expression of SNHG14 predicted poor prognosis in patients with HCC. SNHG14 promoted proliferation and metastasis of HCC cells. We further revealed that SNHG14 functioned as a competing endogenous RNA (ceRNA) for miR-876-5p and that SSR2 was a downstream target of miR-876-5p in HCC. Transwell, CCK8 and animal experiments exhibited miR-876-5p inhibited HCC progression in vitro and in vivo. By conducting rescue experiments, we found the overexpression of SSR2 or knocking down the level of miR-876-5p could reverse the suppressive roles of SNHG14 depletion in HCC. Conclusion SNHG14 promotes HCC progress by acting as a sponge of miR-876-5p to regulate the expression of SSR2 in HCC.

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