scholarly journals Upregulated Wnt-11 and miR-21 Expression Trigger Epithelial Mesenchymal Transition in Aggressive Prostate Cancer Cells

Biology ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 52 ◽  
Author(s):  
Elif Damla Arisan ◽  
Ozge Rencuzogullari ◽  
Ines Lua Freitas ◽  
Syanas Radzali ◽  
Buse Keskin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Significant Inhibition ◽  
Developmentally Regulated ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Formalin Fixed Paraffin ◽  
Signaling Axis

Prostate cancer (PCa) is the second-leading cause of cancer-related death among men. microRNAs have been identified as having potential roles in tumorigenesis. An oncomir, miR-21, is commonly highly upregulated in many cancers, including PCa, and showed correlation with the Wnt-signaling axis to increase invasion. Wnt-11 is a developmentally regulated gene and has been found to be upregulated in PCa, but its mechanism is unknown. The present study aimed to investigate the roles of miR-21 and Wnt-11 in PCa in vivo and in vitro. First, different Gleason score PCa tissue samples were used; both miR-21 and Wnt-11 expressions correlate with high Gleason scores in PCa patient tissues. This data then was confirmed with formalin-fixed paraffin cell blocks using PCa cell lines LNCaP and PC3. Cell survival and colony formation studies proved that miR-21 involves in cells’ behaviors, as well as the epithelial-mesenchymal transition. Consistent with the previous data, silencing miR-21 led to significant inhibition of cellular invasiveness. Overall, these results suggest that miR-21 plays a significant role related to Wnt-11 in the pathophysiology of PCa.

Wogonoside Inhibits Prostate Cancer Cell Growth and Metastasis via Regulating Wnt/β-Catenin Pathway and Epithelial-Mesenchymal Transition

Pharmacology ◽  
2019 ◽  
Vol 104 (5-6) ◽  
pp. 312-319 ◽  
Author(s):  
Can Wei ◽  
Junfeng Jing ◽  
Yanbin Zhang ◽  
Ling Fang
Keyword(s):  
Prostate Cancer ◽  
Cell Viability ◽  
Epithelial Mesenchymal Transition ◽  
Phase Cell ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Pc3 Cells ◽  
Gsk 3Β

Background: Wogonoside, an effective component of Scutellaria baicalensis extract, has recently become a hot topic for its newly discovered anticancer efficacy, but the underlying pharmacological mechanism is still unclear. In this study, we tested the inhibitory effects of wogonoside in human prostate cancer PC3 cells in vitro and vivo. Methods: The effects of wogonoside on cell viability, cycle progression, invasion, migration, and apoptosis were assessed in vitro. The levels of proteins in related signaling pathways were detected by western blotting assay. Finally, nude mouse tumorigenicity assay was conducted to detect the anticancer effect of wogonoside in vivo. Results: Wogonoside inhibited cell viability, invasive and migratory ability in a time- and dose-dependent manner. Flow cytometry indicated that wogonoside could induce cell apoptosis and S phase cell-cycle arrest. Mechanically, wogonoside suppressed the Wnt/β-catenin signaling pathway, and the level of p-glycogen synthase kinase-3β (GSK-3β; Ser9) was inhibited by wogonoside. The epithelial-mesenchymal transition (EMT) process was also reversed in PC3 cell line after wogonoside treatment. In vivo experiments showed that wogonoside inhibited tumor growth in xenograft mouse models. Conclusion: These findings revealed that wogonoside could suppress Wnt/β-catenin pathway and reversing the EMT process in PC3 cells. GSK-3β acts as a tumor suppressor in prostate cancer. Wogonoside may serve as an effective agent for treating prostate cancer.

scholarly journals MiR-130a-3p inhibits the viability, proliferation, invasion, and cell cycle, and promotes apoptosis of nasopharyngeal carcinoma cells by suppressing BACH2 expression

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Xin Chen ◽  
Bo Yue ◽  
Changming Zhang ◽  
Meihao Qi ◽  
Jianhua Qiu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Down Regulation ◽  
Tissue Samples ◽  
Mesenchymal Transition

The aim of the present study was to explore the mechanism through which miR-130a-3p affects the viability, proliferation, migration, and invasion of nasopharyngeal carcinoma (NPC). Tissue samples were collected from the hospital department. NPC cell lines were purchased to conduct the in vitro and in vivo assays. A series of biological assays including MTT, Transwell, and wound healing assays were conducted to investigate the effects of miR-130a-3p and BACH2 on NPC cells. MiR-130a-3p was down-regulated in both NPC tissues and cell lines, whereas BACH2 was up-regulated in both tissues and cell lines. MiR-130a-3p overexpression inhibited NPC cell viability, proliferation, migration, and invasion but promoted cell apoptosis. The converse was true of BACH2, the down-regulation of which could inhibit the corresponding cell abilities and promote apoptosis of NPC cells. The target relationship between miR-130a-3p and BACH2 was confirmed. The epithelial–mesenchymal transition (EMT) pathway was also influenced by miR-130a-3p down-regulation. In conclusion, miR-130a-3p could bind to BACH2, inhibit NPC cell abilities, and promote cell apoptosis.

scholarly journals SMARCC1 Suppresses Tumor Progression by Inhibiting the PI3K/AKT Signaling Pathway in Prostate Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhao-Ming Xiao ◽  
Dao-Jun Lv ◽  
Yu-zhong Yu ◽  
Chong Wang ◽  
Tao Xie ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Proliferation And Metastasis ◽  
Cell Proliferation And Metastasis

BackgroundSWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily C member 1 (SMARCC1) protein is a potential tumor suppressor in various cancers. However, its role in prostate cancer (PCa) remains controversial. The aim of this study was to determine the biological function of SMARCC1 in PCa and explore the underlying regulatory mechanisms.MethodsThe expression of SMARCC1 was validated in PCa tissues by immunohistochemistry. Meanwhile, function experiments were used to evaluate the regulatory role on cell proliferation and metastasis in PCa cells with SMARCC1 depletion both in vitro and in vivo. The expression levels of relevant proteins were detected by Western blotting.ResultsOur finding showed that SMARCC1 was significantly downregulated in prostate adenocarcinoma, with a higher Gleason score (GS) than that in low GS. The decreased expression of SMARCC1 was significantly correlated with a higher GS and poor prognosis. Additionally, we found that silencing of SMARCC1 dramatically accelerated cell proliferation by promoting cell cycle progression and enhancing cell migration by inducing epithelial mesenchymal transition (EMT). Furthermore, depletion of SMARCC1 facilitated PCa xenograft growth and lung metastasis in murine models. Mechanistically, the loss of SMARCC1 activated the PI3K/AKT pathway in PCa cells.ConclusionSMARCC1 suppresses PCa cell proliferation and metastasis via the PI3K/AKT signaling pathway and is a novel therapeutic target.

scholarly journals MiR-543 Promotes Proliferation and Epithelial-Mesenchymal Transition in Prostate Cancer via Targeting RKIP

2017 ◽  
Vol 41 (3) ◽  
pp. 1135-1146 ◽  
Author(s):  
Yang Du ◽  
Xiu-heng Liu ◽  
Heng-cheng Zhu ◽  
Lei Wang ◽  
Jin-zhuo Ning ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
In Vivo Studies ◽  
Mesenchymal Transition ◽  
Proliferation And Metastasis

Background/Aims: MicroRNAs (miRNAs, miRs) have emerged as important post-transcriptional regulators in various cancers. miR-543 has been reported to play critical roles in hepatocellular carcinoma and colorectal cancer, however, the role of miR-543 in the pathogenesis of prostate cancer has not been fully understood. Methods: Expression of miR-543 and Raf Kinase Inhibitory Protein (RKIP) in clinical prostate cancer specimens, two prostate cancer cell lines, namely LNCAP and C4-2B, were determined. The effects of miR-543 on proliferation and metastasis of tumor cells were also investigated with both in vitro and in vivo studies. Results: miR-543 was found to be negatively correlated with RKIP expression in clinical tumor samples and was significantly upregulated in metastatic prostate cancer cell line C4-2B compared with parental LNCAP cells. Further studies identified RKIP as a direct target of miR-543. Overexpression of miR-543 downregulated RKIP expression and promoted the proliferation and metastasis of cancer cells, whereas knockdown of miR-543 increased expression of RKIP and suppressed the proliferation and metastasis of cancer cells in vitro and in vivo. Conclusion: Our study demonstrates that miR-543 promotes the proliferation and metastasis of prostate cancer via targeting RKIP.

scholarly journals Overexpression of Glypican 5 (GPC5) Inhibits Prostate Cancer Cell Proliferation and Invasion via Suppressing Sp1-Mediated EMT and Activation of Wnt/β-Catenin Signaling

2018 ◽  
Vol 26 (4) ◽  
pp. 565-572 ◽  
Author(s):  
Yu Sun ◽  
Kai Xu ◽  
Miao He ◽  
Guilian Fan ◽  
Hongming Lu
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Cell Proliferation ◽  
Mesenchymal Transition ◽  
The Family ◽  
Signaling Activation ◽  
Proliferation And Invasion

Glypican 5 (GPC5) belongs to the family of heparan sulfate proteoglycans (HSPGs). It was initially known as a regulator of growth factors and morphogens. Recently, there have been reports on its correlation with the tumorigenic process in the development of some cancers. However, little is known about its precise role in prostate cancer (PCa). In the present study, we explored the expression pattern and biological functions of GPC5 in PCa cells. Our results showed that GPC5 was lowly expressed in PCa cell lines. Upregulation of GPC5 significantly inhibited PCa cell proliferation and invasion in vitro as well as attenuated tumor growth in vivo. We also found that overexpression of GPC5 inhibited the epithelial‐mesenchymal transition (EMT) and Wnt/β-catenin signaling activation, which was mediated by Sp1. Taken together, we suggest GPC5 as a tumor suppressor in PCa and provide promising therapeutic strategies for PCa.

scholarly journals SP1 Initiates Epithelial-Mesenchymal Transition of CTCs and Inhibits Metastasis in Prostate Cancer

2021 ◽  
Author(s):  
Mei Yang ◽  
Hui Liu ◽  
Guo Ping Qiu ◽  
Fei Gao
Keyword(s):  
Prostate Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Clinical Trial Registry ◽  
Mesenchymal Transition ◽  
Bioinformatics Software ◽  
Local Pca

Abstract Background: Circulating tumor cells （CTCs）are the basis of cancer metastasis. Till now, the role of different subtypes of CTCs in metastasis is unclear. Methods: We used the CanpatrolTM technique to isolate CTCs from 102 prostate cancer (PCa) patients. The EMT markers of CTCs were detected by FISH and classified CTCs into Epethial (E-CTCs), Mesenchymal (M-CTCs) and Mesenchymal/Epethial-CTCs (M/E-CTCs). Further, the potential EMT related molecules regulators were predicted by bioinformatics software, and SP1 was identified as the key EMT regulator. Then overexpress SP1 of PCa cells to verify the effect of SP1 on the EMT regulation and PCa metastasis. Results: The count of Total-CTCs, E-CTCs, and M/E-CTCs in metastatic PCa was significantly higher than that in local PCa. Although M-CTCs was not significantly different between local and metastatic PCa, the ratio of M-CTCs/Total-CTCs in metastatic PCa was markedly lower than that in local PCa. We found that Total-CTCs is an independent risk factor for PCa metastasis. Overexpression of SP1 initiated EMT of PCa cells and enhanced the invasion in vitro. Injecting overexpression SP1 PCa cells via tail vein, generating M-CTCs in vivo, we found the ability of M-CTCs to form lung metastasis was significantly inhibited compared with that of the control PCa-CTCs. Conclusion: Our study suggested Total-CTCs >14 predict PCa metastasis. M/E-CTCs might facilitate to PCa metastasis; however, M-CTCs might not. SP1 is an EMT regulator, which has the potential role of regulating the EMT of CTCs, thus changing the proportion of subtypes of CTCs. It is a potential therapeutic target.（Trial registration: Chinese Clinical Trial Registry. Registered 30 JUNE 2020, http://www.chictr.org.cn/registry.aspx）

scholarly journals Knockdown of microRNA-214-3p Promotes Tumor Growth and Epithelial-Mesenchymal Transition in Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5875
Author(s):  
Patrice Cagle ◽  
Nikia Smith ◽  
Timothy O. Adekoya ◽  
Yahui Li ◽  
Susy Kim ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Protein Tyrosine Kinase ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Oncogenic Signaling ◽  
Mesenchymal Transition

Abnormal expression of microRNA miR-214-3p (miR-214) is associated with multiple cancers. In this study, we assessed the effects of CRISPR/Cas9 mediated miR-214 depletion in prostate cancer (PCa) cells and the underlying mechanisms. Knockdown of miR-214 promoted PCa cell proliferation, invasion, migration, epithelial-mesenchymal transition (EMT), and increased resistance to anoikis, a key feature of PCa cells that undergo metastasis. The reintroduction of miR-214 in miR-214 knockdown cells reversed these effects and significantly suppressed cell proliferation, migration, and invasion. These in vitro studies are consistent with the role of miR-214 as a tumor suppressor. Moreover, miR-214 knockout increased tumor growth in PCa xenografts in nude mice supporting its anti-oncogenic role in PCa. Knockdown of miR-214 increased the expression of its target protein, Protein Tyrosine Kinase 6 (PTK6), a kinase shown to promote oncogenic signaling and tumorigenesis in PCa. In addition, miR-214 modulated EMT as exhibited by differential regulation of E-Cadherin, N-Cadherin, and Vimentin both in vitro and in vivo. RNA-seq analysis of miR-214 knockdown cells revealed altered gene expression related to PCa tumor growth pathways, including EMT and metastasis. Collectively, our findings reveal that miR-214 is a key regulator of PCa oncogenesis and is a potential novel therapeutic target for the treatment of the disease.

scholarly journals Loss of p63 and its microRNA-205 target results in enhanced cell migration and metastasis in prostate cancer

2012 ◽  
Vol 109 (38) ◽  
pp. 15312-15317 ◽  
Author(s):  
Paola Tucci ◽  
Massimiliano Agostini ◽  
Francesca Grespi ◽  
Elke K. Markert ◽  
Alessandro Terrinoni ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Epithelial Mesenchymal Transition ◽  
Inhibitory Effect ◽  
Data Set ◽  
Mesenchymal Transition ◽  
Metastatic Behavior ◽  
A Cell

p63 inhibits metastasis. Here, we show that p63 (both TAp63 and ΔNp63 isoforms) regulates expression of miR-205 in prostate cancer (PCa) cells, and miR-205 is essential for the inhibitory effects of p63 on markers of epithelial–mesenchymal transition (EMT), such as ZEB1 and vimentin. Correspondingly, the inhibitory effect of p63 on EMT markers and cell migration is reverted by anti–miR-205. p53 mutants inhibit expression of both p63 and miR-205, and the cell migration, in a cell line expressing endogenous mutated p53, can be abrogated by pre–miR-205 or silencing of mutated p53. In accordance with this in vitro data, ΔNp63 or miR-205 significantly inhibits the incidence of lung metastasis in vivo in a mouse tail vein model. Similarly, one or both components of the p63/miR-205 axis were absent in metastases or colonized lymph nodes in a set of 218 human prostate cancer samples. This was confirmed in an independent clinical data set of 281 patients. Loss of this axis was associated with higher Gleason scores, an increased likelihood of metastatic and infiltration events, and worse prognosis. These data suggest that p63/miR-205 may be a useful clinical predictor of metastatic behavior in 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 Wnt-11 Expression Promotes Invasiveness and Correlates with Survival in Human Pancreatic Ductal Adeno Carcinoma

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 921 ◽  
Author(s):  
Dart ◽  
Arisan ◽  
Owen ◽  
Hao ◽  
Jiang ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Ductal Adenocarcinoma ◽  
Boyden Chamber ◽  
Mrna Levels ◽  
Rna Seq ◽  
Developmentally Regulated ◽  
Mesenchymal Transition ◽  
Adeno Carcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer, proving difficult to manage clinically. Wnt-11, a developmentally regulated gene producing a secreted protein, has been associated with various carcinomas but has not previously been studied in PDAC. The present study aimed to elucidate these aspects first in vitro and then in a clinical setting in vivo. Molecular analyses of Wnt-11 expression as well as other biomarkers involved qRT-PCR, RNA-seq and siRNA. Proliferation was measured by MTT; invasiveness was quantified by Boyden chamber (Matrigel) assay. Wnt-11 mRNA was present in three different human PDAC cell lines. Wnt-11 loss affected epithelial-mesenchymal transition and expression of neuronal and stemness biomarkers associated with metastasis. Indeed, silencing Wnt-11 in Panc-1 cells significantly inhibited their Matrigel invasiveness without affecting their proliferative activity. Consistently with the in vitro data, human biopsies of PDAC showed significantly higher Wnt-11 mRNA levels compared with matched adjacent tissues. Expression was significantly upregulated during PDAC progression (TNM stage I to II) and maintained (TNM stages III and IV). Wnt-11 is expressed in PDAC in vitro and in vivo and plays a significant role in the pathophysiology of the disease; this evidence leads to the conclusion that Wnt-11 could serve as a novel, functional biomarker PDAC.

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