scholarly journals Trophoblast proliferation, migration, and invasion is regulated by the miR-195/EGFR signaling pathway in recurrent spontaneous abortion patients

2019 ◽  
Author(s):  
Xue Bai ◽  
Chunyang Zheng ◽  
Na Ren
Keyword(s):  
Signaling Pathway ◽  
Spontaneous Abortion ◽  
Recurrent Spontaneous Abortion ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Egfr Signaling ◽  
Trophoblast Cells ◽  
Egfr Signaling Pathway

ABSTRACTOBJECTIVETo investigate the effect of the miR-195/EGFR signaling pathway on trophoblasts in patients with recurrent spontaneous abortion, thus providing a clinical basis for the diagnosis and treatment of recurrent spontaneous abortion.METHODSRT-qPCR, western blot, flow cytometry, CCK8, cell scratch assay, transwell, and a dual Luciferase reporter assay were used to detect changes in the miR-195/EGFR signaling pathways in clinical samples and in vitro cultured cells and to explore how these changes affect trophoblasts in affected patients.RESULTSExpression of miR-195 was elevated in villus tissues of patients with recurrent spontaneous abortion, while the expression levels of EGFR and its downstream genes p38 and AKT phosphorylation were down-regulated. In vitro cultured cell experiments showed that miR-195 inhibited the proliferation, migration, and invasion of trophoblast cells. EGFR is a target gene of miR-195, and miR-195 suppresses the expression of EGFR.ConclusionThe miR-195/EGFR signaling pathway regulates the proliferation, migration, and invasion of trophoblast cells, thus playing an important role in recurrent spontaneous abortion.

scholarly journals Foxq1 promotes metastasis of nasopharyngeal carcinoma by inducing vasculogenic mimicry via the EGFR signaling pathway

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Yunfan Luo ◽  
Jie Wang ◽  
Fan Wang ◽  
Xiong Liu ◽  
Juan Lu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Signaling Pathway ◽  
Target Selection ◽  
Vasculogenic Mimicry ◽  
Luciferase Reporter ◽  
Egfr Signaling ◽  
Luciferase Reporter Gene ◽  
Egfr Signaling Pathway ◽  
Novel Target

AbstractIn nasopharyngeal carcinoma (NPC), the treatment of tumor metastasis and recurrence is challenging and is associated with poor clinical efficacy. Vasculogenic mimicry (VM) is a new blood-supply model of malignant tumor that is closely related to tumors’ distant metastasis. Our previous study demonstrated that miR-124 could target Foxq1 to inhibit NPC metastasis. Whether Foxq1 affects metastasis through vasculogenic mimicry is worth consideration. In this study, we show that VM formation positively correlates with the expression of Foxq1, and EGFR, and the TNM stage in 114 NPC patient samples. Meanwhile, we show that VM-positive NPC patients have a poor prognosis. Furthermore, using in vitro and vivo approaches, we confirm that Foxq1 has a significant effect on NPC metastasis through promoting VM formation, which could be effectively inhibited by EGFR inhibitors (Nimotuzumab or Erlotinib). Also a synergistic efficacy of anti-EGFR and anti-VEGF drugs has been found in NPC inhibition. Mechanistically, the luciferase reporter gene and CHIP assays show that Foxq1 directly binds to the EGFR promoter region and regulates EGFR transcription. In conclusion, our results show that Foxq1 is regulated by miR-124 and that it promotes NPC metastasis by inducing VM via the EGFR signaling pathway. Overall, these results provide a new theoretical support and a novel target selection for anti-VM therapy in the treatment of nasopharyngeal carcinoma.

scholarly journals Has-miR-875-5p Inhibits Tumorigenesis by Targeting USF2 via TGF-β Signaling Pathway in Gastric Cancer

2021 ◽  
Author(s):  
Shenshuo Gao ◽  
Zhikai Zhang ◽  
Xubin Wang ◽  
Yan Ma ◽  
Chensheng Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Research Direction ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
New Research

Abstract Background: Gastric cancer (GC) is one of the most common malignancies, and more and more evdiences show that the pathogenesis is regulated by various miRNAs.In this study, we investigated the role of miR-875 in GC. Methods:The expression of miR-875-5p was detected in human GC specimens and cell lines by miRNA RT-PCR. The effect of miR-875-5p on GC proliferation was determined by CCK-8 proliferation assay and EDU assay. Migration and invasion were examined by transwell migration and invasion assay and wound healing assay. The interaction between miR-875-5p and its target gene USF2 was verified by a dual luciferase reporter assay. The effects of miR-875-5p in vivo were studied in xenograft nude mice models.Related proteins were detected by Western blot.Results:The results showed that miR-875-5p inhibited the proliferation, migration and invasion of gastric cancer cells in vitro, and inhibited tumorigenesis in vivo. USF2 proved to be a direct target of miR-875-5p. Knockdown of USF2 partially counteracts the effects of miR-875-5p inhibitors.Overexpression of miR-875-5p can inhibit proliferation, migration, and invasion through the TGF-β signaling pathway by down-regulation of USF2 in GC, providing a new research direction for the diagnosis and targeted therapy of GC.Conclusions: MiR-875-5pcan inhibited the progression of GC by directly targeting USF2 and negatively regulating TGF-β signaling pathway.In the future, miR-875-5p is expected to be used as a potential therapeutic target for GC therapy.

scholarly journals Long Non-Coding RNA CCAT2 Promotes the Development of Esophageal Squamous Cell Carcinoma by Inhibiting miR-200b to Upregulate the IGF2BP2/TK1 Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaodan Wu ◽  
Yihui Fan ◽  
Yupeng Liu ◽  
Biao Shen ◽  
Haimin Lu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Non Coding Rna

Long non-coding RNAs (lncRNAs) have been shown to play important roles in human cancers, including esophageal squamous cell carcinoma (ESCC). In the current study, we identified CCAT2 as a relevant lncRNA and investigated its role in the progression of ESCC. RT-qPCR was adopted to detect CCAT2 expression in collected clinical samples, ESCC cell lines, and a normal cell line. We tested the correlation between CCAT2 expression and the prognosis of ESCC. RT-qPCR or immunoblotting was adopted to detect the expression of relevant factors in ESCC tissues or cells. Cell proliferation, apoptosis, migration, and invasion were examined by colony formation assay, flow cytometry, scratch assay, and Transwell assay, respectively, while subcutaneous tumorigenesis in nude mice was adopted to examine the role of CCAT2 in tumorigenesis of ESCC cells in vivo. Bioinformatics analysis, dual luciferase reporter assay, and RIP were conducted for the target relationship profiling. Me-RIP was adopted to detect m6A modification level of TK1 in ESCC tissues or cells. Upregulated CCAT2, IGF2BP2, and TK1 expression and inhibited miR-200b expression were observed in ESCC cells and tissues. CCAT2 bound to miR-200b and reduced its expression, leading to upregulated IGF2BP2 expression. IGF2BP2 improved TK1 mRNA stability to enhance its expression by recognizing its m6A modification. CCAT2 promoted the migration and invasion of ESCC cells in vitro, and tumorigenesis in vivo by upregulating TK1 expression, while overexpression of miR-200b reversed these effects of CCAT2. Overall, this study suggests that CCAT2 competitively binds to miR-200b to alleviate its inhibitory effects on IGF2BP2 expression, resulting in elevated TK1 expression, and an ensuing promotion of the development of ESCC.

scholarly journals EPDR1, Which Is Negatively Regulated by miR-429, Suppresses Epithelial Ovarian Cancer Progression via PI3K/AKT Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhendan Zhao ◽  
Zhiling Wang ◽  
Pengling Wang ◽  
Shujie Liu ◽  
Yingwei Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Figo Stage ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gynecology And Obstetrics

Epithelial ovarian cancer (EOC) is the main pathological type of ovarian cancer. In this study, we found that ependymin-related 1 (EPDR1) was remarkably downregulated in EOC tissues, and low EPDR1 expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage, metastasis, and poor prognosis. We confirmed that EPDR1 overexpression dramatically suppressed EOC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, EPDR1 inhibited EOC tumorigenesis and progression, at least in part, through the repression of the PI3K (Phosphoinositide 3-kinase)/AKT (AKT Serine/Threonine Kinase 1) signaling pathway. Furthermore, the expression and function of EPDR1 were regulated by miR-429, as demonstrated by luciferase reporter assays and rescue experiments. In conclusion, our study validated that EPDR1, negatively regulated by miR-429, played an important role as a tumor-suppressor gene in EOC development via inhibition of the PI3K/AKT pathway. The miR-429/EPDR1 axis might provide novel therapeutic targets for individualized treatment of EOC patients in the future.

Role of EGFL7/EGFR-signaling pathway in migration and invasion of growth hormone-producing pituitary adenomas

2018 ◽  
Vol 61 (8) ◽  
pp. 893-901 ◽  
Author(s):  
Qian Liu ◽  
Junwen Zhang ◽  
Hua Gao ◽  
Taoyang Yuan ◽  
Jie Kang ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Signaling Pathway ◽  
Pituitary Adenomas ◽  
Migration And Invasion ◽  
Egfr Signaling ◽  
Egfr Signaling Pathway

scholarly journals DRAM1 plays a tumor suppressor role in NSCLC cells by promoting lysosomal degradation of EGFR

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Ji Geng ◽  
Rong Zhang ◽  
Xiao Yuan ◽  
Haidong Xu ◽  
Zhou Zhu ◽  
...  
Keyword(s):  
In Vivo Studies ◽  
Migration And Invasion ◽  
Egfr Signaling ◽  
Lysosomal Degradation ◽  
Cell Lung Carcinoma ◽  
Lung Cancers ◽  
Lysosomal Ph ◽  
Egfr Signaling Pathway

Abstract Lung cancer is the leading cause of cancer-associated mortality worldwide. DNA damage-regulated autophagy modulator 1 (DRAM1) plays an important roles in autophagy and tumor progression. However, the mechanisms by which DRAM1 inhibits tumor growth are not fully understood. Here, we report that DRAM1 was decreased in nonsmall-cell lung carcinoma (NSCLC) and was associated with poor prognosis. We confirmed that DRAM1 inhibited the growth, migration, and invasion of NSCLC cells in vitro. Furthermore, overexpression of DRAM1 suppressed xenografted NSCLC tumors in vivo. DRAM1 increased EGFR endocytosis and lysosomal degradation, downregulating EGFR signaling pathway. On one side, DRAM1 interacted with EPS15 to promote EGFR endocytosis, as evidence by the results of proximity labeling followed by proteomics; on the other, DRAM1 recruited V-ATP6V1 subunit to lysosomes, thereby increasing the assemble of the V-ATPase complex, resulting in decreased lysosomal pH and increased activation of lysosomal proteases. These two actions of DRAM1 results in acceleration of EGFR degradation. In summary, these in vitro and in vivo studies uncover a novel mechanism through which DRAM1 suppresses oncogenic properties of NSCLC by regulating EGFR trafficking and degradation and highlights the potential value of DRAM1 as a prognostic biomarker in lung cancers.

scholarly journals Abnormal Cullin1 neddylation-mediated p21 accumulation participates in the pathogenesis of recurrent spontaneous abortion by regulating trophoblast cell proliferation and differentiation

2020 ◽  
Author(s):  
Xiaohe Sun ◽  
Xiaomei Tong ◽  
Yanqing Hao ◽  
Chao Li ◽  
Yinli Zhang ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
In Vitro Study ◽  
First Trimester ◽  
Trophoblast Cell ◽  
Recurrent Spontaneous Abortion ◽  
Extravillous Trophoblast ◽  
Clinical Samples ◽  
Biological Regulation ◽  
Gata3 Expression

Abstract The study explores the role of neddylation in early trophoblast development and its alteration during the pathogenesis of recurrent spontaneous abortion (RSA). Immunofluorescence and western blot were conducted to evaluate the expression pattern of NEDD8 protein in the first-trimester placentas of healthy control and RSA patients. Neddylated-cullins, especially neddylated-cullin1, were downregulated and their substrate, p21, was accumulated in RSA samples. NEDD8 cytoplasmic recruitment was observed in extravillous trophoblast (EVT) progenitors of RSA placentas. Consistent with the results of clinical samples, neddylation inhibition using MLN4924 in trophoblast cell lines caused obvious p21 accumulation and free NEDD8 cytoplasmic recruitment. Further in vitro study demonstrated neddylation inhibition attenuated proliferation of Jeg-3 cells via p21 accumulation. Moreover, when trophoblast stem (TS) cells derived from first-trimester placentas were cultured for differentiation analyses. MLN4924 impaired the differentiation of TS cells towards EVTs by downregulating HLA-G and GATA3. p21 knockdown could partly rescue MLN4924-suppressed HLA-G and GATA3 expression. In conclusion, cullin1 neddylation-mediated p21 degradation is required for trophoblast proliferation and can affect trophoblast plasticity by affecting HLA-G and GATA3 expression. The results provide insights into the pathological mechanism of RSA and the biological regulation of trophoblast development.

scholarly journals miR-29a-3p inhibits endometrial cancer cell proliferation, migration and invasion by targeting VEGFA/CD C42/PAK1

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aizhi Geng ◽  
Lin Luo ◽  
Fengyun Ren ◽  
Ling Zhang ◽  
Haiying Zhou ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Signaling Pathway ◽  
Scratch Test ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Ec Cells ◽  
Formation Experiment

Abstract Background This study aimed to investigate the mechanism of miR-29a-3p in regulating endometrial cancer (EC) progression. Methods A total of 72 EC patients were enrolled. EC cells were transfected. Cells proliferation, cloning ability, migration and invasion were researched by MTT assay, colony formation experiment, cell scratch test and Transwell experiment respectively. Dual-luciferase reporter assay was performed. Xenograft experiment was conducted using nude mice. miR-29a-3p, VEGFA, CDC42, PAK1 and p-PAK1 expression in cells/tissues was investigated by qRT-PCR and Western blot. Results miR-29a-3p expression was aberrantly reduced in EC patients, which was associated with poor outcome. miR-29a-3p inhibited EC cells proliferation, cloning formation, migration and invasion (P <  0.05 or P <  0.01 or P <  0.001). miR-29a-3p inhibited CDC42/PAK1 signaling pathway activity in EC cells (P <  0.01). VEGFA expression was directly inhibited by miR-29a-3p. miR-29a-3p suppressed EC cells malignant phenotype in vitro and growth in vivo by targeting VEGFA/CDC42/PAK1 signaling pathway (P < 0.05 or P < 0.01). Conclusion miR-29a-3p inhibits EC cells proliferation, migration and invasion by targeting VEGFA/CDC42/PAK1 signaling pathway.

scholarly journals Quercetin Attenuates Podocyte Apoptosis of Diabetic Nephropathy Through Targeting EGFR Signaling

2022 ◽  
Vol 12 ◽  
Author(s):  
Yiqi Liu ◽  
Yuan Li ◽  
Liu Xu ◽  
Jiasen Shi ◽  
Xiujuan Yu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Growth Factor Receptor ◽  
Network Pharmacology ◽  
Egfr Signaling ◽  
Egfr Signaling Pathway ◽  
Novel Approach ◽  
Apoptotic Protein ◽  
Epidermal Growth

Podocytes injury is one of the leading causes of proteinuria in patients with diabetic nephropathy (DN), and is accompanied by podocytes apoptosis and the reduction of podocyte markers such as synaptopodin and nephrin. Therefore, attenuation of podocyte apoptosis is considered as an effective strategy to prevent the proteinuria in DN. In this study, we evaluated the anti-podocyte-apoptosis effect of quercetin which is a flavonol compound possessing an important role in prevention and treatment of DN and verified the effect by using db/db mice and high glucose (HG)-induced mouse podocytes (MPs). The results show that administration of quercetin attenuated the level of podocyte apoptosis by decreasing the expression of pro-apoptotic protein Bax, cleaved caspase 3 and increasing the expression of anti-apoptotic protein Bcl-2 in the db/db mice and HG-induced MPs. Furthermore, epidermal growth factor receptor (EGFR) was predicted to be the potential physiological target of quercetin by network pharmacology. In vitro and vivo experiments confirmed that quercetin inhibited activation of the EGFR signaling pathway by decreasing phosphorylation of EGFR and ERK1/2. Taken together, this study demonstrates that quercetin attenuated podocyte apoptosis through inhibiting EGFR signaling pathway, which provided a novel approach for further research of the mechanism of quercetin in the treatment of DN.

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