scholarly journals Circular RNA circ0005276 promotes the proliferation and migration of prostate cancer cells by interacting with FUS to transcriptionally activate XIAP

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Yang Feng ◽  
Yuxuan Yang ◽  
Xiaodan Zhao ◽  
Yameng Fan ◽  
Long Zhou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rna ◽  
Host Gene ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Human Cancers ◽  
Apoptosis Protein ◽  
And Migration ◽  
And Function

Abstract Prostate cancer (PCa) is one of the major men’s malignancies with high mortality worldwide. Circular RNAs (circRNAs) have been shown to serve as essential regulators in human cancers. CircRNA can exert their functions by cooperating with their host genes. In the present study, microarray analysis revealed an upregulated mRNA in PCa samples. X-linked inhibitor of apoptosis protein (XIAP), a key regulator in the progression of human cancers. Through bioinformatics analysis, we determined that XIAP is a host gene for circRNA0005276. Therefore, this study focused on the interaction between circ0005276 and XIAP as well as their functions in PCa progression. The upregulation of XIAP and circ0005276 was determined in PCa tissues and cell lines. Moreover, we confirmed the positive regulation of circ0005276 on XIAP expression. Functionally, we validated that circ0005276 and XIAP promoted cell proliferation, migration and epithelial–mesenchymal transition. Mechanistically, we verified that circ0005276 interacted with FUS binding protein (FUS) so as to activate the transcription of XIAP. Rescue assays were conducted to determine the crucial role of XIAP in circ0005276 and FUS-mediated PCa cellular processes. Collectively, our study revealed the mechanism and function of circ0005276 and its host gene XIAP in PCa progression.

scholarly journals Circular RNA hsa_circ_0003288 induces EMT and invasion by regulating hsa_circ_0003288/miR-145/PD-L1 axis in hepatocellular carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guili Xu ◽  
Peng Zhang ◽  
Hansi Liang ◽  
Yunhua Xu ◽  
Jian Shen ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Circular Rna ◽  
In Vivo Studies ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Huh7 Cells ◽  
And Function

Abstract Background Epithelial-mesenchymal transition (EMT) has been associated with wound healing, tumorigenesis, and metastasis. Circular RNAs (circRNAs) are functional non-coding RNAs involved in multiple human cancers. However, whether and how circRNAs contribute to the EMT in hepatocellular carcinomas (HCC) remains to be deciphered. In this study, we investigated the regulation and function of hsa_circ_0003288 on programmed death-1 ligand 1 (PD-L1) during EMT and HCC invasiveness. Methods Hsa_circ_0003288 expression was measured by real-time quantitative reverse transcriptase PCR (qRT-PCR). Luciferase reporter assays, RNA pull-down assay and fluorescence in situ hybridization (FISH) were used to determine the correlation between hsa_circ_0003288 and miR-145 and between miR-145 and PD-L1. Furthermore, ectopic overexpression and siRNA-mediated downregulation of hsa_circ_0003288, transwell assays, and in vivo studies were used to determine the function of hsa_circ_0003288 on the EMT and invasiveness of L02 and HCC cells. Results miR-145 directly targeted the PD-L1 3′-untranslated region (UTR) region, and hsa_circ_0003288 acted as a miR-145 sponge to regulate PD-L1 expression. Overexpression of hsa_circ_0003288 increased PD-L1 levels and promoted EMT, migration, and invasiveness of L02 cells. These observations were reversed after knockdown of hsa_circ_0003288 in HepG2 and Huh7 cells. Overexpression of PD-L1 rescued EMT, migration, and invasiveness of HepG2 and Huh7 cells after knockdown of hsa_circ_0003288. Furthermore, hsa_circ_0003288 knockdown reduced EMT in in vivo studies. Hsa_circ_0003288/PD-L1 axis was found to mediate the metastatic phenotypes via the PI3K/Akt pathway in HCC. Additionally, expression levels of hsa_circ_0003288 were increased and positively correlated with PD-L1 expression in HCC tissues. Conclusion Our findings demonstrated that hsa_circ_0003288 promoted EMT and invasion of HCC via the hsa_circ_0003288/miR-145/PD-L1 axis through the PI3K/Akt pathway. Targeting hsa_circ_0003288 may be a therapeutic strategy for the treatment of HCC.

scholarly journals EMT Participates in the Regulation of Exosomes Secretion and Function in Esophageal Cancer Cells

2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Chuangui Chen ◽  
Zhao Ma ◽  
Hongjing Jiang
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Promoting Effect ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration ◽  
And Function ◽  
Esophageal Cancer Cells

Epithelial-mesenchymal transition (EMT) is a key step in tumor invasion and distant metastasis. Abundant evidence has documented that exosomes can mediate EMT of tumor cells and endow them with the ability of invasion and migration. However, there are few studies focusing on whether EMT can reverse the secretion of exosomes. In this study, 2 esophageal cancer cells (FLO-1 and SK-GT-4) were selected to compare the migration ability and EMT activation, and to further analyze the secretion ability of exosomes of the 2 cell lines. According to the results, inhibited activation of EMT in FLO-1 cells with relatively high migration ability could effectively reduce the secretion of exosomes. Besides, in SK-GT-4 cells, EMT activation induced by TGF-β could promote the secretion of exosomes. FLO-1 cell derived exosomes exhibited a paracrine effect of promoting the migration of SK-GT-4 cells, and the use of EMT inhibitors could weaken this ability. Furthermore, inhibition of EMT could change the relative content of some miRNAs in exosomes, with a particularly significant downregulation in the expression of miR-196-5p, miR-21-5p and miR-194-5p. Significantly, artificial transfection of the 3 miRNAs into exosomes by electroporation resulted in the recovery of migration-promoting effect of exosomes. Subsequent experiments further revealed that the effect of EMT on these miRNAs could be explained by the intracellular transcription level or the specific sorting mechanism of exosomes. To sum up, our study undoubtedly reveals that EMT has a regulatory effect on exosomes in the quantity and contents in esophageal cancer cells. Significantly, findings in our study provide experimental evidence for the interaction of EMT with the secretion and sorting pathway of exosomes, and also give a new direction for the further study of tumor metastasis.

scholarly journals Hsa_circRNA_102002 facilitates metastasis of papillary thyroid cancer through regulating miR-488-3p/HAS2 axis

2020 ◽  
Author(s):  
Wei Zhang ◽  
Ting Liu ◽  
Tianshu Li ◽  
Xudong Zhao
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Xenograft Model ◽  
Inhibitory Effect ◽  
Circular Rnas ◽  
Papillary Thyroid ◽  
Mesenchymal Transition ◽  
Mouse Xenograft Model ◽  
And Migration

Abstract As important modulators in various physiological processes, circular RNAs (circRNAs) have been increasingly demonstrated in tumors, including papillary thyroid cancer (PTC). Hsa_circRNA_102002 (circ_102002) is a circRNA derived from alternative splicing of ubiquitin-specific peptidase 22 (USP22) transcript, the role of which needs further investigation. Our results suggested the upregulation of circ_102002 in PTC tissues and cells, and its promoting effects on epithelial–mesenchymal transition (EMT) and cell migration. Mechanism studies showed that circ_102002 could sponge microRNA-488-3p (miR-488-3p) and downregulate its expression. The target relationship between miR-488-3p and hyaluronic acid synthetase 2 (HAS2) in PTC was systematically studied. In addition, our results showed that HAS2 overexpression could restore the inhibited cell EMT and migration. Moreover, the inhibitory effect of downregulation of circ_102002 on PTC growth was evaluated in a mouse xenograft model, which involved miR-488-3p and HAS2 regulation. These findings about the signal axis of circ_102002/miR-488-3p/HAS2 may further elucidate the PTC pathogenesis and improve clinical treatment.

Bone Marrow-Derived Mesenchymal Stem Cells (BMSCs)-Derived MicroRNA-378a-3p (miR-378a-3p) Inhibits the Migration of Gestational Trophoblast Cells and Epithelial Mesenchymal Transition via Regulating X-Linked Inhibitor of Apoptosis Protein (XIAP) Pathway

2021 ◽  
Vol 11 (10) ◽  
pp. 1983-1989
Author(s):  
Juan Du ◽  
Qinghong Ji ◽  
Lihua Dong ◽  
Yanping Meng ◽  
Gang Xin
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Migration And Invasion ◽  
Trophoblastic Cell ◽  
Mesenchymal Transition ◽  
Apoptosis Protein ◽  
And Migration ◽  
Injury Progression ◽  
Proliferation And Migration

The components of the in vivo microenvironment are BMSCs and miRNAs that have a critical role in the development of pregnancy. Our aim was to further investigate the effect of the miRNAs of BMSC origin on pregnancy injury. Exosomal miR-378a-3p secreted by BMSCs was identified by electron microscopy and miR-378a-3p expression was measured during gestational injury. Target scan detects the correlation of XIAP and miR-378a-3p which was confirmed by luciferase activity along with analysis of cell growth by MTT assay and cell invasion by Transwell and EMT expression. Exosomal miR-378a-3p derived from BMSCs promoted proliferation and migration and invasion of trophoblast. miR-378a-3p targeted XIAP and its overexpression could significantly increase EMT switching. The miR-378a-3p/XIAP axis is critical in trophoblastic cell migration and EMT and is involved in pregnancy injury progression, indicating that it might be a novel potential target for the treatment of pregnancy injury.

scholarly journals Periostin Mediates TGF-β-Induced Epithelial Mesenchymal Transition in Prostate Cancer Cells

2015 ◽  
Vol 36 (2) ◽  
pp. 799-809 ◽  
Author(s):  
Qingfeng Hu ◽  
Shijun Tong ◽  
Xiaojun Zhao ◽  
Weihong Ding ◽  
Yuancheng Gou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Western Blot ◽  
Cancer Cells ◽  
Cell Invasion ◽  
Associated Factors ◽  
Epithelial Mesenchymal Transition ◽  
Prostate Cancer Cells ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration

Background: In our previous study, we found that periostin was upregulated in prostate cancer, and its expression could be modulated by TGF-β. TGF-β could upregulate periostin expression in some cells, and both TGF-β and periostin could induce epithelial mesenchymal transition (EMT). We aimed to study the effect of periostin in the process of TGF-β-induced EMT in prostate cancer cells. Methods: We constructed a lentivirus vector containing the periostin gene and transduced it into PC3 and DU145 cells. After confirming periostin overexpression by PCR and Western blotting, we used an MTT assay to establish a growth curve to measure cell proliferation. Additionally, we performed transwell and wound healing assays to measure cell invasion and migration, respectively. Lastly, we measured the expression of EMT associated factors using Western blot analysis to test the effect of periostin on EMT in prostate cancer cells. Results: PCR and Western blot analyses confirmed that periostin was upregulated after infection with the periostin lentiviral vector. Periostin overexpression promoted increased cell proliferation, invasion, and migration as measured by MTT, transwell, and wound healing assays, respectively. Western blot analysis illustrated that periostin overexpression increased the expression of EMT associated factors, and periostin overexpression activated Akt and GSK-3β, which could be inhibited using a PI3K inhibitor. Additionally, TGF-β increased the levels of STAT3, Twist1 and periostin, while both STAT3 shRNA and Twist1 shRNA inhibited periostin expression. However, STAT3 shRNA also decreased Twist1 expression. Although reduction of STAT3, Twist1 or periostin levels with shRNA inhibited TGF-β-induced overexpression of EMT associated factors, periostin overexpression could reverse such inhibition by interfering with STAT3 and Twist1. Similarly, periostin overexpression also reversed inhibition of cell invasion induced by interference of STAT3 and Twist1. Conclusion: Our findings indicate that periostin is an important mediator of TGF-β-induced EMT and suggest that periostin is a potential therapeutic target for suppressing the metastatic progression of prostate cancer.

scholarly journals The Significance of Circular RNA DDX17 in Prostate Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Qi Lin ◽  
Jian Cai ◽  
Qin-Quan Wang
Keyword(s):  
Prostate Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Tissue Samples ◽  
Inorganic Pyrophosphate ◽  
Mesenchymal Transition ◽  
Rna Immunoprecipitation ◽  
Reporter Assays

Circular RNA DDX17 (circDDX17) has been demonstrated as a tumor suppressor in colorectal cancer. However, mechanisms underlying circDDX17 effects in cases of prostate cancer (PCa) are not well understood. Thus, herein, we determined measures of circDDX17 expression by use of the TCGA database. Expression of circDDX17 in prostate cancer-afflicted tissue samples was determined by qRT-PCR. Functionally, circDDX17 induced remarkable inhibition of cell colonizing ability, invasion, and epithelial-mesenchymal transition (EMT) progression in vitro. Mechanistically, dual-luciferase reporter assays, RNA immunoprecipitation, and RNA pull-down experiments helped verify interactions between circDDX17 and miR-346. Low expression of circDDX17 occurred in TCGA PCa samples. Furthermore, circDDX17 expression was downregulated significantly in PCa. These results suggested that circDDX17 suppressed PC cell mobility, proliferation, and invasion. Mechanistic experiments indicated that circDDX17 might serve as a ceRNA of miR-346 to relieve repressive effects of miR-346 upon phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP). LHPP expression itself was downregulated in TCGA PCa samples. Overall, our findings indicated that the circDDX17/miR-346/LHPP pathway inhibited the progression of prostate cancer and that circDDX17 may be a new potential therapeutic or diagnostic target for treating and diagnosing prostate cancer. As our study also demonstrated for the first time that LHPP might act as an anticancer gene in prostate cancer, the findings could have wide-ranging implications for the treatment of this affliction.

scholarly journals CircACAP2 promotes cell proliferation and migration in lung adenocarcinoma via LASP1-mediated TGF‐β/Smad3 pathway

2021 ◽  
Author(s):  
Jianyu Xu ◽  
Jianli Ma ◽  
Bixi Guan ◽  
Jian Li ◽  
Yan Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Regulatory Mechanism ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Lung adenocarcinoma (LUAD), a common malignant tumor, has led to a great number of deaths around the world. Circular RNAs (circRNAs) have been certified as essential players in the progression of diverse cancers. CircRNA ACAP2 (hsa_circ_0068568) is an oncogene in several cancers. However, the role of circACAP2 in LUAD remains unknown. This study revealed that the expression of circACAP2 was significantly elevated in LUAD tissues and cell lines, especially in the tissues of LUAD patients at advanced stage. Additionally, circACAP2 enhanced cell proliferation, migration, invasion abilities and epithelial-mesenchymal transition (EMT) process in LUAD. Moreover, miR-342-3p interacted with circACAP2 in LUAD cells. Importantly, we found that miR-342-3p targeted LIM and SH3 protein 1 (LASP1), and circACAP2 positively regulated LASP1 expression by competing for miR-342-3p in LUAD. Further, it was confirmed that circACAP2 promoted the malignant behaviors and stimulated the activation of TGF-β/Smad3 pathway in LUAD by modulating the miR-342-3p/LASP1 axis. To conclude, the molecular regulatory mechanism of circACAP2 in LUAD was under discussion in the current study. The findings revealed that circACAP2 facilitated malignant phenotypes in LUAD via the activation of the TGF‐β/Smad3 pathway.

scholarly journals SPP1 Promotes Enzalutamide Resistance and EMT Activation in CRPC Progression via PI3K/AKT and ERK1/2 Pathways

2021 ◽  
Author(s):  
Xiaocong Pang ◽  
Junling Zhang ◽  
Xu He ◽  
Yanlun Gu ◽  
Wei Yu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Strong Relationship ◽  
Castration Resistant Prostate Cancer ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Castration Resistant ◽  
And Migration

Abstract The bottleneck arising from castration-resistant prostate cancer (CRPC) treatment is its high metastasis potential and anti-androgen drug resistance, which severely affects survival time of prostate cancer (PCa) patients. In our previous study, we firstly revealed SPP1 was a potential hub signature for predicting metastatic CRPC (mCRPC) development. Herein, we integrated multiple databases to explore the association of SPP1 expression with prognosis, survival, metastatic levels in CRPC progression, and also investigated SPP1 expression in PCa tissues and cell lines. Next, PCa cell lines with overexpression or depletion of SPP1 were established to study the effect of SPP1 on enzalutamide sensitivity, and adhesion and migration of prostate cancer cell lines and further explore the underlying regulatory mechanisms. Bioinformatics analysis, PCR, immunohistochemical staining and western blot results suggested SPP1 upregulation had strong relationship with the malignant progression of CRPC. SPP1 knockdown repressed enzalutamide sensitivity, invasion and migration of prostate cancer cells in vitro. Importantly, upregulating SPP1 promoted, while silencing SPP1 attenuated epithelial-mesenchymal-transition (EMT). Our results further demonstrate that SPP1 overexpression maintains the activation of PI3K/AKT signaling and ERK1/2 pathways. Overall, our findings unraveled the functional role and clinical significance of SPP1 in PCa progression, and help to discover new potential targets against mCRPC.

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