KCNQ1OT1 accelerates gastric cancer progression via miR-4319/DRAM2 axis

Introduction: This work was to explore the connection of KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) and microRNA-4319 (miR-4319), and to investigate the associated underlying mechanisms in gastric cancer (GC) progression. Methods: Quantitative real-time PCR was performed to measure KCNQ1OT1, miR-4319 and DNA-damage regulated autophagy modulator 2 (DRAM2) expression levels in GC cells. Moreover, expression level of KCNQ1OT1 and DRAM2 in GC tissues was analyzed at ENCORI website ( http://starbase.sysu.edu.cn/index.php ). Cell proliferation, colony formation assay and flow cytometry assays were performed to analyze effects of KCNQ1OT1, miR-4319 and DRAM2 on cell growth and death. Dual-luciferase activity reporter assay and RNA immunoprecipitation assay was conducted to verify the interactions of KCNQ1OT1 or DRAM2 and miR-4319. Results and Conclusion: We found KCNQ1OT1 level was increased in tumor tissues and cells. Force the expression of KCNQ1OT1 promotes, while knockdown KCNQ1OT1 inhibits GC cell growth. Further studies indicated miR-4319 functioned as a bridge between KCNQ1OT1 and DRAM2. Finally, we showed KCNQ1OT1/miR-4319/DRAM2 axis regulates GC cell growth in vitro and in vivo. lncRNA KCNQ1OT1 promotes GC progression by sponging miR-4319 to upregulate DRAM2, indicating KCNQ1OT1 might be a promising target for GC treatment.

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Linc00473 potentiates cholangiocarcinoma progression by modulation of DDX5 expression via miR-506 regulation

10.21203/rs.3.rs-25881/v2 ◽

2020 ◽

Author(s):

Lining Huang ◽

Xingming Jiang ◽

Zhenglong Li ◽

Jinglin Li ◽

Xuan Lin ◽

...

Keyword(s):

Cell Lines ◽

Cancer Progression ◽

Luciferase Reporter ◽

Loss Of Function ◽

Qrt Pcr ◽

Competitive Endogenous Rnas ◽

Rna Immunoprecipitation ◽

Underlying Mechanisms

Abstract Background: Cholangiocarcinoma (CCA) is a mortal cancer with high mortality, whereas the function and mechanism of occurrence and progression of CCA are still mysterious. Long non-coding RNAs (lncRNAs) could function as important regulators in carcinogenesis and cancer progression. Growing evidences have indicated that the novel lncRNA linc00473 plays an important role in cancer progression and metastasis. However, its function and molecular mechanism in CCA remain unknown. Methods: The linc00473 expression in CCA tissues and cell lines was analyzed using qRT-PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of linc00473 both in vitro and in vivo. Insights into the underlying mechanisms of competitive endogenous RNAs (ceRNAs) were determined by bioinformatics analysis, dual-luciferase reporter assays, qRT-PCR arrays, RNA immunoprecipitation (RIP) and rescue experiments. Results: Linc00473 was highly expressed in CCA tissues and cell lines. Linc00473 knockdown inhibited CCA growth and metastasis. Furthermore, linc00473 acted as miR-506 sponge and regulated its target gene DDX5 expression. Rescue assays verified that linc00473 modulated the tumorigenesis of CCA by regulating miR-506. Conclusions: The data indicated that linc00473 played an oncogenic role in CCA growth and metastasis, and could serve as a novel molecular target for treating CCA.

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circEVI5 acts as a miR-4793-3p sponge to suppress the proliferation of gastric cancer

Cell Death and Disease ◽

10.1038/s41419-021-04061-4 ◽

2021 ◽

Vol 12 (8) ◽

Author(s):

Meinan Yan ◽

Liling Niu ◽

Jing Liu ◽

Yuan Yao ◽

Hui Li

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Circular Rnas ◽

Tissue Samples ◽

Expression Levels ◽

Rna Immunoprecipitation ◽

Incorporation Assay ◽

Underlying Mechanisms

AbstractCircular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs (ncRNAs) with a covalently closed loop structure. Accumulating evidence shows that circRNAs play vital roles in the growth, metastasis, treatment and prognosis of various cancers. However, the detailed functions and underlying mechanisms of circEVI5 (hsa_circ_0013162) in gastric cancer (GC) remain undocumented. In this study, the expression levels and prognostic value of circEVI5 were validated in GC tissue samples by using qRT-PCR. circEVI5 was significantly downregulated in GC tissues and cells, and low circEVI5 expression was correlated with poor prognosis. Next, in vitro CCK-8 assay, EdU incorporation assay, PI staining cell cycle assay, and in vivo xenograft mouse models were conducted to assess the functions of circEVI5. Gain of function experiments indicated that circEVI5 could inhibit GC cell proliferation and retard the cell cycle. Moreover, bioinformatics prediction showed that circEVI5 binds to miR-4793-3p, while FOXO1 may be a target of miR-4793-3p. Pull-down assays, RNA immunoprecipitation (RIP) assays, luciferase assays, and western blot were used to confirm the interactions between circEVI5, miR-4793-3p, and FOXO1. Functional assays demonstrated that circEVI5 suppressed the proliferation of GC by sponging miR-4793-3p and increasing FOXO1 expression levels. In conclusion, our study demonstrated that circEVI5 can bind miR-4793-3p as a ceRNA to eliminate the negative regulation of FOXO1, therefore suppressing GC proliferation.

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Linc00473 potentiates cholangiocarcinoma progression by modulation of DDX5 expression via miR-506 regulation

10.21203/rs.3.rs-25881/v1 ◽

2020 ◽

Author(s):

Lining Huang ◽

Xingming Jiang ◽

Zhenglong Li ◽

Jinglin Li ◽

Xuan Lin ◽

...

Keyword(s):

Cell Lines ◽

Cancer Progression ◽

Luciferase Reporter ◽

Loss Of Function ◽

Qrt Pcr ◽

Competitive Endogenous Rnas ◽

Rna Immunoprecipitation ◽

Underlying Mechanisms

Abstract Background Cholangiocarcinoma (CCA) is a mortal cancer with high mortality, whereas the function and mechanism of occurrence and progression of CCA are still mysterious. Long non-coding RNAs (lncRNAs) could function as important regulators in carcinogenesis and cancer progression. Growing evidences have indicated that the novel lncRNA linc00473 plays an important role in cancer progression and metastasis. However, its function and molecular mechanism in CCA remain unknown. Methods The linc00473 expression in CCA tissues and cell lines was analyzed using qRT-PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of linc00473 both in vitro and in vivo. Insights into the underlying mechanisms of competitive endogenous RNAs (ceRNAs) were determined by bioinformatics analysis, dual-luciferase reporter assays, qRT-PCR arrays, RNA immunoprecipitation (RIP) and rescue experiments. Results Linc00473 was highly expressed in CCA tissues and cell lines. Linc00473 knockdown inhibited CCA growth and metastasis. Furthermore, linc00473 acted as miR-506 sponge and regulated its target gene DDX5 expression. Rescue assays verified that linc00473 modulated the tumorigenesis of CCA by regulating miR-506. Conclusions The data indicated that linc00473 played an oncogenic role in CCA growth and metastasis, and could serve as a novel molecular target for treating CCA.

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Linc00473 potentiates cholangiocarcinoma progression by modulation of DDX5 expression via miR-506 regulation

10.21203/rs.3.rs-25881/v3 ◽

2020 ◽

Author(s):

Lining Huang ◽

Xingming Jiang ◽

Zhenglong Li ◽

Jinglin Li ◽

Xuan Lin ◽

...

Keyword(s):

Cell Lines ◽

Cancer Progression ◽

Luciferase Reporter ◽

Loss Of Function ◽

Qrt Pcr ◽

Competitive Endogenous Rnas ◽

Rna Immunoprecipitation ◽

Underlying Mechanisms

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Long Non-coding RNA FIRRE Acts as a miR-520a-3p Sponge to Promote Gallbladder Cancer Progression via Mediating YOD1 Expression

Frontiers in Genetics ◽

10.3389/fgene.2021.674653 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shuqing Wang ◽

Yang Wang ◽

Shouhua Wang ◽

Huanjun Tong ◽

Zhaohui Tang ◽

...

Keyword(s):

Gallbladder Cancer ◽

Cancer Progression ◽

Clinical Stage ◽

Luciferase Reporter ◽

Tumor Tissues ◽

Rna Immunoprecipitation ◽

Reporter Assays ◽

And Migration

ObjectivesThe role of lncRNAs in gallbladder cancer (GBC) remains poorly understood. In this study, we explored the function of functional intergenic repeating RNA element (FIRRE) in GBC.Materials and MethodsWhole transcriptome resequencing was performed in three pairs of GBC tissues and adjacent non-tumor tissues. lncRNA FIRRE expression was verified by real-time PCR. The function of FIRRE in GBC was evaluated by experiments in vitro and in vivo. The mechanism of FIRRE was investigated via fluorescent in situ hybridization, RNA pull-down, dual luciferase reporter assays, and RNA immunoprecipitation.ResultsFIRRE level was dramatically increased in GBC tissues compared to that in the adjacent non-tumor tissues. High expression of FIRRE was closely related to clinical stage and poor prognosis in GBC patients. Moreover, FIRRE remarkably enhanced proliferation and migration, and inhibited apoptosis of GBC cells. Mechanistically, FIRRE modulated YOD1 expression by sponging miR-520a-3p, thus contributing to the development of GBC.ConclusionOur data revealed that FIRRE might act as a novel mediator in GBC progression by sponging miR-520a-3p and regulating YOD1. FIRRE might be regarded as a potential diagnostic marker or target for GBC treatment.

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HOXC-AS1-MYC regulatory loop contributes to the growth and metastasis in gastric cancer

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-019-1482-7 ◽

2019 ◽

Vol 38 (1) ◽

Cited By ~ 2

Author(s):

Yangyang Dong ◽

Xinyu Li ◽

Zhibin Lin ◽

Wenbing Zou ◽

Yan Liu ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Growth ◽

Luciferase Reporter ◽

Gene Expressions ◽

In Vivo Experiments ◽

Promising Target ◽

Reporter Assays ◽

Regulatory Loop

Abstract Background Gastric cancer (GC) is one of the most prevalent and deadly malignancies worldwide. Accumulating reports have indicated the participation of long non-coding RNAs (lncRNAs) in the onset and progression of GC. Methods GSE109476 data was utilized to screen out lncRNAs dysregulated in GC. Gene expressions were determined by qRT-PCR and western blot. Both in vitro and in vivo experiments were carried out to assess the function of HOXC-AS1 in GC. The association between genes was verified via RIP, ChIP, CoIP, RNA pull down and luciferase reporter assays, as appropriate. Results HOXC-AS1 was discovered to be upregulated in GC and located both in cytoplasm and in nucleus in GC cells. Functionally, inhibition of HOXC-AS1 restrained GC cell growth and metastasis both in vitro and in vivo. Moreover, HOXC-AS1 was proved to be trans-activated by c-MYC in GC. In return, HOXC-AS1 positively regulated MYC expression in GC through targeting miR-590-3p/MYC axis in cytoplasm and modulating BRG1/β-catenin complex-activated MYC transcription in nucleus. Furthermore, the rescue assays verified that MYC mediated HOXC-AS1-affected GC progression. Conclusion Our research illustrated a feedback loop of HOXC-AS1-MYC in aggravating GC cell growth and metastasis, highlighting HOXC-AS1 as a promising target for GC diagnosis and treatment.

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MiR-375 reduces the stemness of gastric cancer cells through triggering ferroptosis

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02394-7 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Haiwei Ni ◽

Hai Qin ◽

Cheng Sun ◽

Yichen Liu ◽

Guojing Ruan ◽

...

Keyword(s):

Gastric Cancer ◽

Ectopic Expression ◽

Luciferase Reporter ◽

Gastric Cancer Cells ◽

Stress Markers ◽

In Vivo Experiments ◽

Rna Immunoprecipitation ◽

Underlying Mechanisms

Abstract Background Gastric cancer stem cells (CSCs) are the main causes of metastasis and drug resistance. We previously indicated that miR-375 can inhibit Helicobacter pylori-induced gastric carcinogenesis; here, we aim to explore the effects and mechanisms of miR-375 on gastric cancer (GC) cell stemness. Methods Lentivirus infection was used to construct GC cells with ectopic expression of miR-375. In vitro and in vivo experiments, including analysis of tumor spheroid formation, CD44+ sub-population with stemness, stemness marker expression, and tumor-initiating ability, were performed to evaluate the effects of miR-375 on the stemness of GC cells. Furthermore, microarray and bioinformatics analysis were performed to search the potential targets of miR-375 in GC cells. Luciferase reporter, RNA immunoprecipitation, and RNA-FISH assays were carried out to verify the targeting of miR-375. Subsequently, combined with tissue microarray analysis, erastin-resistant GC cells, transmission electron microscopy, a series of agonists and oxidative stress markers, the underlying mechanisms contributing to miR-375-mediated effects were explored. Results MiR-375 reduced the stemness of GC cells in vitro and in vivo. Mechanistically, SLC7A11 was identified as a direct target of miR-375 and miR-375 attenuated the stemness of GC cells mainly through triggering SLC7A11-dependent ferroptosis. Conclusion MiR-375 can trigger the ferroptosis through targeting SLC7A11, which is essential for miR-375-mediated inhibition on GC cell stemness. These results suggest that the miR-375/SLC7A11 regulatory axis could serve as a potential target to provoke the ferroptosis and thus attenuate the stemness of GC cells.

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Novel Findings of Anti-cancer Property of Propofol

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666170912120327 ◽

2018 ◽

Vol 18 (2) ◽

pp. 156-165 ◽

Cited By ~ 8

Author(s):

Jiaqiang Wang ◽

Chien-shan Cheng ◽

Yan Lu ◽

Xiaowei Ding ◽

Minmin Zhu ◽

...

Keyword(s):

General Anesthesia ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Intravenous Anesthetic ◽

The Past ◽

Anti Cancer ◽

Underlying Mechanisms ◽

Recent Attention

Background: Propofol, a widely used intravenous anesthetic agent, is traditionally applied for sedation and general anesthesia. Explanation: Recent attention has been drawn to explore the effect and mechanisms of propofol against cancer progression in vitro and in vivo. Specifically, the proliferation-inhibiting and apoptosis-inducing properties of propofol in cancer have been studied. However, the underlying mechanisms remain unclear. Conclusion: This review focused on the findings within the past ten years and aimed to provide a general overview of propofol's malignance-modulating properties and the potential molecular mechanisms.

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Knockout of Ajuba Attenuates the Growth and Migration of Hepatocellular Carcinoma Cells

Cytogenetic and Genome Research ◽

10.1159/000512264 ◽

2020 ◽

Vol 160 (11-12) ◽

pp. 650-658

Author(s):

Yichen Le ◽

Yi He ◽

Meirong Bai ◽

Ying Wang ◽

Jiaxue Wu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Growth ◽

Cancer Progression ◽

Normal Liver ◽

Cell Growth And Migration ◽

And Migration ◽

Hcc Cells

Ajuba has been found to be mutated or aberrantly regulated in several human cancers and plays important roles in cancer progression via different signaling pathways. However, little is known about the role of Ajuba in hepatocellular carcinoma (HCC). Here, we found an upregulation of Ajuba expression in HCC tissues compared with normal liver tissues, while a poor prognosis was observed in HCC patients with high Ajuba expression. Knockout of Ajuba in HCC cells inhibited cell growth in vitro and in vivo, suppressed cell migration, and enhanced the cell apoptosis under stress. Moreover, re-expression of Ajuba in Ajuba-deficient cells could restore the phenotype of Ajuba-deficient cells. In conclusion, these results indicate that Ajuba is upregulated in HCC and promotes cell growth and migration of HCC cells, suggesting that Ajuba could possibly be a new target for HCC diagnosis and treatment.

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

Cell Death and Disease ◽

10.1038/s41419-020-03316-w ◽

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.

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