scholarly journals Astragaloside IV Induced miR-134 Expression Reduces EMT and Increases Chemotherapeutic Sensitivity by Suppressing CREB1 Signaling in Colorectal Cancer Cell Line SW-480

2017 ◽  
Vol 43 (4) ◽  
pp. 1617-1626 ◽  
Author(s):  
Qi Ye ◽  
Li Su ◽  
Dagui Chen ◽  
Wenyi Zheng ◽  
Ye Liu
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cell Migration ◽  
Luciferase Reporter ◽  
Colorectal Cancer Cell Line ◽  
Migration And Invasion ◽  
Astragaloside Iv ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion ◽  
Chemotherapeutic Sensitivity

Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Although chemotherapy is the primary means in colorectal cancer treatment, it is burdenerd by adverse drug effects. Drug-resistance is one of the most important challenges for chemotherapy and epithelial-mesenchymal transition (EMT) plays critical role in the development of drug resistance. Aims: The aim of this study was to investigate the mechanisms underlying the effect of astragaloside IV (AS-IV) on miR-134 expression, EMT and chemotherapeutic sensitivity in CRC. Methods: Cell proliferation, transfection assay, western blot, real-time PCR, cell migration and invasion assay and luciferase reporter assay were used to detect the effects of AS-IV on CRC. Results: AS-IV significantly inhibited CRC cell migration and invasion by inducing miR-134 expression. Moreover, AS-IV and miR-134 increased the sensitivity of CRC tumors to oxaliplatin (OXA) chemotherapy. cAMP responsive element-binding protein 1 (CREB1), which was required for CRC cells migration, invasion and drug sensitivity, was significantly down-regulated by AS-IV. Conclusions: Our results indicated that AS-IV inhibited CRC EMT by inducing miR-134 expression which significantly down-regulated the CREB1 signaling pathway, and therefore increased the sensitivity to chemotherapy. Our findings provided new insight into the mechanisms of chemotherapy-resistant CRC, and may open new therapeutic options in the treatment of this devastating disease.

scholarly journals ASIC1a Stimulates the Resistance of Human Hepatocellular Carcinoma by Promoting Epithelial-mesenchymal Transition via the AKT/GSK3β/Snail Signaling Pathway

2021 ◽  
Author(s):  
Yinci Zhang ◽  
Niandie Cao ◽  
Jiafeng Gao ◽  
Jiaojiao Liang ◽  
Yong Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Cell Migration ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion ◽  
Gsk 3Β ◽  
Hcc Cells

Abstract Background: The main obstacle to the cure of hepatocellular carcinoma (HCC) is multidrug resistance. Acid sensing ion channel 1a (ASIC1a) acts as a critical roles in all stages of cancer progression, especially invasion and metastasis as well as in resistance to therapy. Epithelial to mesenchymal transition (EMT) is a phenomenon in which epithelial cells transform into mesenchymal cells after being stimulated by extracellular factors and is closely related to tumor infiltration and resistance. Methods: Western blotting assay, Immunofluorescence (IF) staining, Immunohistochemistry (IHC) staining, MTT and colony formation assay and scratch healing assay were used to detect the level of ASIC1a and the cell proliferation, migration and invasion capabilities in this research.Results: In this research, we found that the protein of ASIC1a is overexpressed in HCC cancer tissues. In addition, we identified that the levels of ASIC1a are highly expressed in resistant HCC cells. Compared with the parental cells, EMT occurred more frequently in drug-resistant cells. Functional studies demonstrated that inactivation of ASIC1a restrained cell migration and invasion and enhanced the chemosensitivity of cells through EMT. In HCC cells, the overexpression of ASIC1a stimulates the up-regulation of EMT characterization molecular level and proliferation, migration and invasion capabilities and further induces drug resistance, while knocking down ASIC1a with short hairpin RNA (shRNA) has the opposite effect. Further investigations found that ASIC1a increased cell migration and invasion through EMT by regulating α and β-catenin, vimentin and fibronectin expression via AKT/GSK-3β/Snail pathway. Conclusions: Our study demonstrated that ASIC1a acts an important assignment in drug resistance of HCC through EMT via AKT/GSK-3β/Snail pathway, thereby lending a latent therapeutic objective and new ideas regarding to HCC.

scholarly journals MiR-200b Suppresses Gastric Cancer Cell Migration and Invasion by Inhibiting NRG1 through ERBB2/ERBB3 Signaling

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Tonglei Xu ◽  
Fangliang Xie ◽  
Dazhou Xu ◽  
Weidong Xu ◽  
Xuming Ge ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Epithelial Mesenchymal Transition ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Neuregulin 1 ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion ◽  
Erbb3 Signaling

Purpose. Accumulating evidence indicates that miRNAs (miRs) play crucial roles in the modulation of tumors development. However, the accurately mechanisms have not been entirely clarified. In this study, we aimed to explore the role of miR-200b in the development of gastric cancer (GC). Methods. Western blot and RT-PCR were applied to detect epithelial-mesenchymal transition (EMT) marker expression and mRNA expression. Transwell assay was used for measuring the metastasis and invasiveness of GC cells. TargetScan system, luciferase reporter assay, and rescue experiments were applied for validating the direct target of miR-200b. Results. MiR-200b was prominently decreased in GC tissues and cells, and its downregulation was an indicator of poor prognosis of GC patients. Reexpression of miR-200b suppressed EMT along with GC cell migration and invasion. Neuregulin 1 (NRG1) was validated as the target of miR-200b, and it rescued miR-200b inhibitory effect on GC progression. In GC tissues, the correlation of miR-200b with NRG1 was inverse. Conclusion. MiR-200b suppressed EMT-related migration and invasion of GC through the ERBB2/ERBB3 signaling pathway via targeting NRG1.

scholarly journals miR-215 Inhibits Colorectal Cancer Cell Migration and Invasion via Targeting Stearoyl-CoA Desaturase

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Xinhua Xu ◽  
Yan Ding ◽  
Jun Yao ◽  
Zhiping Wei ◽  
Haipeng Jin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Target Gene ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Reporter Assay ◽  
Cell Migration And Invasion ◽  
Stearoyl Coa Desaturase

Background. This study was aimed at exploring the effects of miR-215 and its target gene stearoyl-CoA desaturase (SCD) on colorectal cancer (CRC) cell migration and invasion. Methods. Here, we analyzed the relationship between miR-215 and SCD, as well as the regulation of miR-215 on CRC cells. We constructed wild-type and mutant plasmids of SCD to identify whether SCD was a target gene of miR-215 by using a luciferase reporter assay. The expression of miR-215 and SCD was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. MTT, wound healing, and Transwell assays were applied to determine the effect of miR-215 on CRC cell proliferation, migration, and invasion. Results. It was found that miR-215 expression was significantly decreased in CRC tissue while SCD was highly expressed compared with those in adjacent normal tissue. The luciferase reporter assay indicated that SCD was a direct target gene of miR-215. Functional analysis revealed that miR-215 overexpression significantly inhibited CRC cell proliferation, migration, and invasion in vitro. In addition, the result of rescue experiments showed that overexpression of SCD could promote the proliferation, migration, and invasion of CRC cells, and the carcinogenic effect of SCD could be inhibited by miR-215. Conclusions. Taken together, our findings suggested that miR-215 could inhibit CRC cell migration and invasion via targeting SCD. The result could eventually contribute to the treatment for CRC.

scholarly journals FOXF2-Mediated lncRNA LINC02532 Promotes Gastric Cancer Cell Migration and Invasion By Decreasing SOX7 mRNA Stability

2021 ◽  
Author(s):  
Cheng Zhang ◽  
Chun-Dong Zhang ◽  
Jun-Peng Pei ◽  
Yong-Zhi Li ◽  
Maimaititusun Yusupu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcriptional Regulation ◽  
Cell Migration ◽  
Mrna Stability ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion

Abstract Background LncRNAs are known to play a crucial role in the initiation and progression of human diseases, especially cancers. Our previous study demonstrated that dysregulation of LINC02532 facilitated the malignant phenotype of gastric cancer (GC). However, the potential molecular mechanisms regarding the upstream and downstream regulation of LINC02532 in GC progression remain unclear. Methods RNA-Seq and clinical data from public databases were used for gene expression and clinical analyses. The subcellular location of LINC02532 was predicted by the bioinformatics tools and further validated by the RNA-Fluorescence in situ hybridization (FISH) assay. The effect of FOXF2/LINC02532/SOX7 axis in GC cell migration and invasion was evaluated using in vitro and in vivo assays. The transcriptional regulation role of FOXF2 and the mRNA stability of SOX7 were explored by dual-luciferase reporter assay and Actinomycin-D drug assay. Results We found that high LINC02532 expression was associated with poor prognosis of GC. Furthermore, a Cox regression model indicated that LINC02532 was an independent prognostic factor for GC patients. Using in vitro and in vivo assays, we found that LINC02532 promoted GC cell migration and invasion, as well as tumour growth and metastasis in nude mice. Mechanistically, LINC02532 decreased SOX7 mRNA stability by binding to its 3’UTR, resulting in reduced SOX7 expression. In addition, FOXF2 was identified as a transcriptional factor of LINC02532 and was shown to repress LINC02532 expression by negative transcriptional regulation. Conclusions Together, these findings show that LINC02532 promotes GC progression through epithelial–mesenchymal transition (EMT). Cross-talk between the FOXF2/LINC02532/SOX7 axis may provide a novel target for the treatment and prognostic prediction of GC.

scholarly journals MiR-27b-3p promotes migration and invasion in colorectal cancer cells by targeting HOXA10

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Xiangling Yang ◽  
Junxiong Chen ◽  
Yao Liao ◽  
Lanlan Huang ◽  
Chuangyu Wen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Tumor Progression ◽  
Luciferase Reporter Assay ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Reporter Assay ◽  
Integrin Β1 ◽  
Cell Migration And Invasion

Abstract Purpose: Dysregulation of microRNAs (miRNAs) contributes to tumor progression via the regulation of the expression of specific oncogenes and tumor suppressor genes. One such example, miR-27b-3p, has reportedly been involved in tumor progression in many types of cancer. The aim of the present study was to delve into the role and the underlying mechanism of miR-27b-3p in colorectal cancer (CRC) cells. Methods: In the present study, we detected the expression level of miR-27b-3p by RT-PCR. The effect of miR-27b-3p overexpression on cell proliferation in CRC cells was evaluated by cell counting and Edu assays. Transwell migration and invasion assays were used to examine the effects of cell migration and invasion. Bioinformatics, luciferase reporter assay and western blot assay were performed to identify the target of miR-27b-3p. Results: Here, we have demonstrated that although miR-27b-3p can affect cell morphology, it has no observable effect on the proliferation of CRC cells. However, it significantly promotes the migration and invasion of CRC cells. We discovered that HOXA10 was a newly identified target of miR-27b-3p in CRC cells, as confirmed by bioinformatics, western blots and dual luciferase reporter assay. Furthermore, the overexpression of miR-27b-3p or the suppression of HOXA10 can activate the integrin β1 signaling pathway. In conclusion, our results reveal a new function of miR-27b-3p that demonstrates its ability to promote CRC cell migration and invasion by targeting the HOXA10/integrin β1 cell signal axis. Conclusion: This may provide a mechanism to explain why miR-27b-3p promotes CRC cell migration and invasion.

scholarly journals MicroRNA-202 inhibits cell migration and invasion through targeting FGF2 and inactivating Wnt/β-catenin signaling in endometrial carcinoma

2019 ◽  
Vol 39 (10) ◽  
Author(s):  
Ping Chen ◽  
Tianrong Xing ◽  
Qingdong Wang ◽  
Ai Liu ◽  
Haiping Liu ◽  
...  
Keyword(s):  
Cell Migration ◽  
Endometrial Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion ◽  
Direct Target Gene ◽  
Ec Cells

Abstract Recently, many mircroRNAs (miRNAs) involved in the development and progression of cancer have been reported to regulate cell growth and metastasis, including microRNA-202 (miR-202). The purpose of the present study was to elucidate the effect of miR-202 on endometrial carcinoma (EC) cell migration and invasion. First, qRT-PCR showed that miR-202 was down-regulated in EC tissues, which was associated with poor prognosis in EC patients. Functionally, transwell assay indicated that miR-202 inhibited cell migration and invasion in EC cells. In addition, miR-202 also blocked epithelial–mesenchymal transition (EMT) through suppressing N-cadherin and Vimentin expressions and promoting E-cadherin expression. Moreover, the dual-luciferase reporter assay showed that fibroblast growth factor 2 (FGF2) is a direct target gene for miR-202 in EC cells. Furthermore, up-regulation of FGF2 attenuated the inhibitory effect of miR-202 on cell migration and invasion in EC. Besides that, miR-202 inactivated the Wnt/β-catenin signaling by suppressing β-catenin expression in EC. In conclusion, miR-202 inhibited cell migration and invasion by targeting FGF2 and inactivating the Wnt/β-catenin signaling in EC.

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