scholarly journals EIF4A3-induced circular RNA PRKAR1B promotes osteosarcoma progression by miR-361-3p-mediated induction of FZD4 expression

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Zhen-hua Feng ◽  
Lin Zheng ◽  
Teng Yao ◽  
Si-yue Tao ◽  
Xiao-an Wei ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
High Throughput ◽  
Crucial Role ◽  
High Throughput Sequencing ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rna ◽  
Potential Therapeutic Target ◽  
Mesenchymal Transition ◽  
Downstream Target ◽  
Underlying Mechanisms

AbstractEmerging evidence indicates that circRNAs are broadly expressed in osteosarcoma (OS) cells and play a crucial role in OS progression. Recently, cancer-specific circRNA circPRKAR1B has been identified by high-throughput sequencing and is recorded in publicly available databases. Nevertheless, the detailed functions and underlying mechanisms of circPRKAR1B in OS remains poorly understood. By functional experiments, we found that circPRKAR1B enhanced OS cell proliferation, migration, and promotes OS epithelial–mesenchymal transition (EMT). Mechanistic investigations suggested that circPRKAR1B promotes OS progression through sponging miR-361-3p to modulate the expression of FZD4. Subsequently, we identified that EIF4A3 promoted cirPRKAR1B formation through binding to the downstream target of circPRKAR1B on PRKAR1B mRNA. Further rescue study revealed that overexpression of the Wnt signalling could impair the onco-suppressor activities of the silencing of circPRKAR1B. Interestingly, further experiments indicated that circPRKAR1B is involved in the sensitivity of chemoresistance in OS. On the whole, our results demonstrated that circPRKAR1B exerted oncogenic roles in OS and suggested the circPRKAR1B/miR-361-3p/FZD4 axis plays an important role in OS progression and might be a potential therapeutic target.

scholarly journals Circular RNA hsa_circ_0007121 regulates proliferation, migration, invasion, and epithelial–mesenchymal transition of trophoblast cells by miR-182-5p/PGF axis in preeclampsia

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 1061-1071
Author(s):  
Shukun Gai ◽  
Li Sun ◽  
Huiying Wang ◽  
Ping Yang
Keyword(s):  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rna ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Relative Level ◽  
Mesenchymal Transition ◽  
Underlying Mechanisms

AbstractBackgroundMounting evidence has revealed that abnormal expression of circular RNAs play pivotal roles in many human diseases including preeclampsia (PE). While human sapiens circular RNA 0007121 (hsa_circ_0007121) has been verified to be downregulated in human placental tissues, the underlying mechanisms were still unclear. This research aims to investigate the effect and underlying mechanisms of hsa_circ_0007121 in preeclampsia.MethodsThe expression of hsa_circ_0007121, microRNA (miR)-182-5p, and placental growth factor (PGF) was assessed by quantitative reverse transcription polymerase chain reaction in PE placentas relative to the expression in normal pregnancy placentas. After transfection, cell counting kit-8 assay was employed to detect cell proliferation. Cell migration and invasion were tested by the transwell assay. The relative level of epithelial–mesenchymal transition (EMT)-related proteins in HTR-8/SVneo cells and PGF in placentas samples were measured by western blot. The relationship between miR-182-5p and hsa_circ_0007121 or PGF was predicated by circular RNA interactome or ENCORI and verified by dual-luciferase reporter assay and RNA immunoprecipitation assay.ResultsThe levels of hsa_circ_0007121 and PGF were significantly declined in PE placental tissues and HTR-8/SVneo cells, whereas miR-182-5p had an opposite result. Downregulation of hsa_circ_0007121 obviously inhibited HTR-8/SVneo cell proliferation, migration, invasion, and EMT, while upregulation of hsa_circ_0007121 promoted this process. Besides, miR-182-5p was a target gene of hsa_circ_0007121 and could target PGF. Further analysis indicated that hsa_circ_0007121 regulated the proliferation, migration, invasion, and EMT of HTR-8/SVneo cells via altering PGF expression by interacting with miR-182-5p.ConclusionHsa_circ_0007121 mediated the progression of PE via miR-182-5p/PGF axis.

scholarly journals Circular RNA CDR1as Inhibits the Metastasis of Gastric Cancer through Targeting miR-876-5p/GNG7 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jiajia Jiang ◽  
Rong Li ◽  
Junyi Wang ◽  
Jie Hou ◽  
Hui Qian ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Luciferase Reporter Gene ◽  
Mesenchymal Transition ◽  
Underlying Mechanisms

Circular RNA CDR1as has been demonstrated to participate in various cancer progressions as miRNA sponges. The exact underlying mechanisms of CDR1as on gastric cancer (GC) metastasis remain unknown. Here, we found that CDR1as knockdown facilitated GC cell migration and invasion while its overexpression inhibited the migration and invasion abilities of GC cells in vitro and in vivo. Moreover, epithelial-mesenchymal transition- (EMT-) associated proteins and MMP2 and MMP9 were downregulated by CDR1as. Bioinformatics analysis combined with dual-luciferase reporter gene assays, western blot, RT-qPCR analysis, and functional rescue experiments demonstrated that CDR1as served as a miR-876-5p sponge and upregulated the target gene GNG7 expression to suppress GC metastasis. In summary, our findings indicate that CDR1as suppresses GC metastasis through the CDR1as/miR-876-5p/GNG7 axis.

scholarly journals LncRNA KRAL suppresses cell growth and increases sensitivity to doxorubicin in osteosarcoma cells by sponging microRNAs-141

2020 ◽  
Vol 18 ◽  
pp. 205873922095990
Author(s):  
Jingwei Cai ◽  
Xiaohui Chen ◽  
Fei Ma ◽  
Jun Qian ◽  
Ming Niu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Luciferase Reporter ◽  
Acquired Drug Resistance ◽  
Mesenchymal Transition ◽  
Downstream Target ◽  
Proliferation Ability ◽  
Enneking Stage

Osteosarcoma (OS) is one of the most common types of malignant tumors characterized by uncontrolled proliferation ability and acquired drug resistance. The previous study indicated that lncRNA KRAL participated in the reversal of 5-FU resistance in liver cancer, but it remains unclear whether lncRNA KRAL involved in doxorubicin (DOX) resistance of osteosarcoma. The expression of lncRNA KRAL and MicroRNAs-141 (miR-141) were detected by RT-qPCR experiment. Also, we used the plasmids transfection to construct the lncRNA KRAL overexpressed OS cell lines. Subsequently, the cell proliferation ability and the sensitivity to DOX in OS cells upon upregulating lncRNA KRAL expression were analyzed via CCK-8 and EDU assay, while western blotting experiment was performed to detect the regulatory mechanism. We found that lncRNA KRAL was downregulated in OS tissues, and the OS patients with OS patients with lower expression of lncRNA KRAL were more likely to have advanced Enneking stage, larger tumor size and distant metastasis. Subsequently, we discovered that upregulation of lncRNA KRAL could inhibit cell proliferation and increase the sensitivity to DOX of OS cells. Interestingly, the western blot results showed that over-expression of lncRNA KRAL could lead to down-expression of P-gp protein and reversal of Epithelial–mesenchymal transition (EMT) pathway. Furthermore, we identified miR-141 as the downstream target gene of lncRNA KRAL, which was further confirmed by the luciferase reporter assay. More importantly, our data demonstrated that addition of miR-141 could reverse cell proliferation and drug sensitivity of lncRNA KRAL-overexpressed OS cells. LncRNA KRAL could suppress cell growth and increases sensitivity to DOX in OS cells by sponging miR-141.

scholarly journals Pterostilbene Alleviates Pulmonary Fibrosis by Regulating ASIC2

2020 ◽  
Author(s):  
Yanfang Peng ◽  
Yingwen Zhang ◽  
Yabing Zhang ◽  
Xiuping Wang ◽  
Yukun Xia ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Western Blot ◽  
High Throughput ◽  
Protein Level ◽  
High Throughput Sequencing ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Mesenchymal Transition ◽  
Tgf Β1

Abstract Background: Idiopathic pulmonary fibrosis (IPF) is a serious chronic disease of the respiratory system, and its current treatment have certain shortcomings and adverse effects. In this study, we evaluate the anti-fibrotic activity of pterostilbene (PTE) using an IPF model induced by TGF-β1 in vitro.Methods: A549 and AEC cells were incubated with 10 ng/ml TGF-β1 to induce lung fibroblast activation. 30 μmol/L PTE was used to treat the cells. The epithelial-mesenchymal transition (EMT), accumulation of extracellular matrix (ECM) and autophagy of cells were suggested by western blot. The apoptosis was proved by flow cytometry analysis and western blot. Transcriptome high-throughput sequencing on A549 cells incubated with TGF-β1 alone or TGF-β1 and PTE (TGF-β1+PTE) was performed, and differentially expressed genes caused by PTE were identified. The ASIC2 overexpression plasmid was used to rescue the protein level of ASIC2 in A549 and AEC cells.Results: TGF-β1 caused the EMT and accumulation of ECM, and blocked the autophagy and apoptosis of A549 and AEC cells. Most importantly, 30 μmol/L PTE inhibited the pulmonary fibrosis induced by TGF-β1. Compared with cells treated with TGF-β1, PTE treatment inhibited the EMT and accumulation of ECM, and rescued cell apoptosis and autophagy. The results of transcriptome high-throughput sequencing performed that PTE greatly reduced the protein level of ASIC2. In addition, compared with the TGF-β1+PTE group, the transfection of ASIC2 overexpression plasmid stimulated the EMT and accumulation of ECM, and inhibited apoptosis and autophagy, suggesting that PTE inhibited pulmonary fibrosis by down-regulating ASIC2. Conclusions: In conclusion, our study suggests that PTE and ASIC2 inhibitors may benefit future IPF treatments.

scholarly journals LncRNA FBXL19-AS1 promotes breast cancer cells proliferation and invasion via acting as a molecular sponge to miR-718

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Zhenmin Ding ◽  
Pengcheng Ye ◽  
Xiaohu Yang ◽  
Hongmiao Cai
Keyword(s):  
Breast Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Potential Therapeutic Target ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
Non Coding Rnas ◽  
Underlying Mechanisms ◽  
Proliferation And Invasion

Abstract Long non-coding RNAs (lncRNAs) have been suggested to serve vital roles in tumor initiation and progression. However, the expression and underlying mechanisms of lncRNA FBXL19-AS1 in breast cancer (BC) remain unclear. In the present study, we found that FBXL19-AS1 expression was significantly up-regulated and correlated with advanced clinical features and poor overall survival of BC patients. Functionally, FBXL19-AS1 inhibition suppressed BC cells proliferation, invasion, and epithelial–mesenchymal transition (EMT) processes in vitro and reduced tumor growth in vivo. In addition, we found that FBXL19-AS1 might function as a ceRNA to sponge miR-718, and miR-718 could rescue the effects of FBXL19-AS1 on BC cells progression. Therefore, these findings suggested that FBXL19-AS1 might serve as an oncogenic lncRNA and promoted BC progression by sponging miR-718, indicating FBXL19-AS1 could serve as a potential therapeutic target for BC treatment.

scholarly journals LncRNA SNHG3 Promotes Proliferation and Metastasis of Non-Small-Cell Lung Cancer Cells Through miR-515-5p/SUMO2 Axis

2021 ◽  
Vol 20 ◽  
pp. 153303382110193
Author(s):  
Yongqun Li ◽  
Lipin Gao ◽  
Caiyun Zhang ◽  
Jiguang Meng
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Downstream Target ◽  
Proliferation And Metastasis ◽  
Study Support ◽  
Cancer Tissues ◽  
Nucleolar Rna

Lung cancer is a global disease and a major cause of cancer-related mortality worldwide. Accumulated studies have confirmed the essential role of long non-coding RNAs (lncRNAs) in the occurrence and development of cancers. Meanwhile, there have been reports concerning the role of Small Nucleolar RNA Host Gene 3 (SNHG3) in various cancers. However, there are so far few studies on the function and mechanism of SNHG3 in lung cancer. In the present study, SNHG3 was found to be highly expressed in lung cancer tissues and cells. Downregulation of SNHG3 could inhibit cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process. In addition, SNHG3 was found to have the ability to bind to miR-515-5p. Furthermore, Small Ubiquitin Like Modifier 2 (SUMO2) was identified to be the downstream target of miR-515-5p, which was negatively correlated with miR-515-5p expression. SNHG3 could positively regulate SUMO2 expression by sponging miR-515-5p. In addition, the rescue experiment showed that simultaneous transfection of miR-515-5p or SUMO2 siRNA could reverse the effect of SNHG3 expression on cell proliferation and metastasis. Collectively, our study demonstrates that SNHG3 can act on miR-515-5p in the form of competitive endogenous RNA (ceRNA) to regulate SUMO2 positively and thus affect the proliferation and metastasis of NSCLC cells. Findings in our study support that SNHG3/miR-515-5p/SUMO2 regulatory axis may become a potential therapeutic target for lung cancer.

scholarly journals CARMA3 Promotes Colorectal Cancer Cell Motility and Cancer Stemness via YAP-Mediated NF-κB Activation

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5946
Author(s):  
Ting-Yu Chang ◽  
Cheng-Tien Wu ◽  
Meei-Ling Sheu ◽  
Rong-Sen Yang ◽  
Shing-Hwa Liu
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Stem Cell Markers ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
Cancer Stem Cell Markers ◽  
Underlying Mechanisms

CARD-recruited membrane-associated protein 3 (CARMA3) is overexpressed in various cancers and is associated with cancer cell proliferation, metastasis, and tumor progression; however, the underlying mechanisms of CARMA3 in colorectal cancer (CRC) metastasis remain unclear. Here, we found that higher CARMA3 expression was correlated with poor overall survival and metastasis in CRC patients from the TNMplot database and Human Tissue Microarray staining. Elevating CARMA3 expression promoted cell proliferation, epithelial-mesenchymal transition (EMT) induction, migration/invasion abilities, sphere formation, and cancer stem cell markers expression. Knockdown of CARMA3 decreased these processes via the EMT-related transcription factor Slug. Moreover, CARMA3 depletion significantly reduced tumor growth in mice that were consistent with the in vitro results. CRC migration/invasion could be regulated by CARMA3/YAP/Slug signaling axis using genetic inhibition of Yes-associated protein (YAP). Interestingly, CARMA3 induced activation of nuclear factor (NF)-κB through YAP expression, contributing to upregulation of Slug. YAP expression positively correlated with CARMA3, NF-κB, and Slug gene expression and poor clinical outcomes in CRC patients. Our findings demonstrate for the first time that CARMA3 plays an important role in CRC progression, which may serve as a potential diagnostic biomarker and candidate therapeutic target for CRC treatment.

Modulation of CD44, EGFR and RAC Pathway Genes (WAVE Complex) in Epithelial Cancers

2019 ◽  
Vol 25 (8) ◽  
pp. 833-848
Author(s):  
Pranathi Tata ◽  
Piyush Gondaliya ◽  
Aditya Sunkaria ◽  
Akshay Srivastava ◽  
Kiran Kalia
Keyword(s):  
Cell Proliferation ◽  
Receptor Tyrosine Kinase ◽  
Crucial Role ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Biology ◽  
Mesenchymal Transition ◽  
Epithelial Cancers ◽  
Cancer Hallmarks ◽  
Proliferation And Invasion ◽  
Wave Complex

Cancer hallmarks help in understanding the diversity of various neoplasms. Epithelial cancers play an immense role in the tumor biology through Epithelial-Mesenchymal Transition (EMT) process. Receptor tyrosine kinase, as well as phosphatidyl ionositol-3 kinase pathways, play an important role in the regulation of cell proliferation, survival, and differentiation during EMT. Till date, numerous studies have shown modulation in the expression profile of potential targets like CD44, EGFR, and Rac in epithelial cancers. CD44 interacts with EGFR and recruits other molecules which further activate the Rac pathway intermediates. This review mainly focused on modulation of genes like CD44, EGFR, and Rac pathway intermediates which play a crucial role in the tumor progression, metastasis, proliferation, and invasion characteristics in epithelial cancers with EMT properties. Hence, targeting Rac pathway might be a more strategically relevant approach in treating epithelial cancers.

scholarly journals Pterostilbene alleviates pulmonary fibrosis by regulating ASIC2

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yanfang Peng ◽  
Yingwen Zhang ◽  
Yabing Zhang ◽  
Xiuping Wang ◽  
Yukun Xia
Keyword(s):  
Pulmonary Fibrosis ◽  
Western Blot ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Alveolar Epithelial Cells ◽  
Mesenchymal Transition ◽  
Tgf Β1

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a serious chronic disease of the respiratory system, but its current treatment has certain shortcomings and adverse effects. In this study, we evaluate the antifibrotic activity of pterostilbene (PTE) using an in vitro IPF model induced by transforming growth factor (TGF)-β1. Methods A549 and alveolar epithelial cells (AECs) were incubated with 10 ng/ml TGF-β1 to induce lung fibroblast activation. Then, 30 μmol/L of PTE was used to treat these cells. The epithelial–mesenchymal transition (EMT), extracellular matrix (ECM) accumulation, and autophagy in cells were evaluated by western blot. Apoptosis was validated by flow cytometry analysis and western blot. Transcriptome high-throughput sequencing was performed on A549 cells incubated with TGF-β1 alone or TGF-β1 and PTE (TGF-β1 + PTE), and differentially expressed genes in PTE-treated cells were identified. The acid sensing ion channel subunit 2 (ASIC2) overexpression plasmid was used to rescue the protein levels of ASIC2 in A549 and AECs. Results TGF-β1 caused EMT and ECM accumulation, and blocked the autophagy and apoptosis of A549 and AECs. Most importantly, 30 μmol/L of PTE inhibited pulmonary fibrosis induced by TGF-β1. Compared with TGF-β1, PTE inhibited EMT and ECM accumulation and rescued cell apoptosis and autophagy. The results of transcriptome high-throughput sequencing revealed that PTE greatly reduced the protein level of ASIC2. Compared with the TGF-β1 + PTE group, the transfection of ASIC2 overexpression plasmid stimulated the EMT and ECM accumulation and inhibited apoptosis and autophagy, suggesting that PTE inhibited pulmonary fibrosis by downregulating ASIC2. Conclusions This study suggests that PTE and ASIC2 inhibitors may have potential as IPF treatments in the future.

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