scholarly journals TRIM50 Suppresses Pancreatic Cancer Progression and Reverses the Epithelial-Mesenchymal Transition via Facilitating the Ubiquitous Degradation of Snail1

2021 ◽  
Vol 11 ◽  
Author(s):  
Rongkun Li ◽  
Lili Zhu ◽  
Yangxizi Peng ◽  
Xiaoxin Zhang ◽  
Chunhua Dai ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Poor Survival ◽  
Mesenchymal Transition ◽  
Functional Roles ◽  
Pancreatic Cancer Cells ◽  
Tripartite Motif ◽  
Cancer Tissues

Emerging evidence suggests that the tripartite motif (TRIM) family play important roles in tumor development and progression. Tripartite motif-containing 50 (TRIM50) is a member of the TRIM family, but little is known regarding its expression and potential functional roles in cancer. In this study, we first analyzed the expression pattern and clinical significance of TRIM50 in pancreatic cancer and found that TRIM50 expression is significantly reduced in pancreatic cancer tissues and its downregulation is associated with poor survival for pancreatic cancer patients. Functionally, TRIM50 overexpression in pancreatic cancer cells decreases their proliferation and motility capabilities and reverses the epithelial-mesenchymal transition (EMT) process, whereas TRIM50 depletion had the opposite effects. Mechanically, TRIM50 directly interacts with Snail1, a key regulator of EMT, and acts as an E3 ubiquitin ligase to target Snail1 for ubiquitous degradation. The function of TRIM50 in suppressing cell migration and EMT depends on TRIM50-promoted Snail1 degradation. In conclusion, our findings identify TRIM50 as a tumor suppressor that inhibits pancreatic cancer progression and reverses EMT via degrading Snail1 and provide new insights into the progression of pancreatic cancer.

scholarly journals Golgi Phosphoprotein 73: The Driver of Epithelial-Mesenchymal Transition in Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yiming Liu ◽  
Xinyang Hu ◽  
Shiyao Liu ◽  
Sining Zhou ◽  
Zhi Chen ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Secretory Protein ◽  
Multifunctional Protein ◽  
Mesenchymal Transition ◽  
Functional Roles ◽  
Research Fields ◽  
Cancer Tissues ◽  
Related Proteins

Golgi phosphoprotein 73 (GP73, also termed as GOLM1 or GOLPH2) is a glycosylated protein residing on cis-Golgi cisternae and highly expressed in various types of cancer tissues. Since GP73 is a secretory protein and detectable in serum derived from cancer patients, it has been regarded as a novel serum biomarker for the diagnosis of different cancers, especially hepatocellular carcinoma (HCC). However, the functional roles of GP73 in cancer development are still poorly understood. In recent years, it has been discovered that GP73 acts as a multifunctional protein-facilitating cancer progression, and strikingly, it has been identified as a leading factor promoting epithelial-mesenchymal transition (EMT) of cancer cells and causing cancer metastasis. In this review, we have overviewed the latest findings of the functional roles of GP73 in elevating cancer progression, especially in facilitating EMT and cancer metastasis through modulating expression, transactivation, and trafficking of EMT-related proteins. In addition, unsolved research fields of GP73 have been lightened, which might be helpful to elucidate the regulatory mechanisms of GP73 on EMT and provide potential approaches in therapeutics against cancer metastasis.

scholarly journals PIK3R3 Promotes Metastasis of Pancreatic Cancer via ZEB1 Induced Epithelial-Mesenchymal Transition

2018 ◽  
Vol 46 (5) ◽  
pp. 1930-1938 ◽  
Author(s):  
Yun-Peng Peng ◽  
Yi Zhu ◽  
Ling-Di Yin ◽  
Ji-Shu Wei ◽  
Xin-Chun Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Cancer ◽  
Regulatory Subunit ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells ◽  
Cancer Tissues

Background/Aims: PIK3R3 is a regulatory subunit of phosphatidylinositol 3-kinase (PI3K) which plays an essential role in the metastasis of several types of cancer. However, whether PIK3R3 can promote the metastasis of pancreatic cancer (PC) is still unclear. In this study, we characterized the role of PIK3R3 in metastasis of PC and underlying potential mechanisms. Methods: RT-PCR, western blot, immunofluorescence (IF) and immunohistochemistry (IHC) were applied to investigate the expression of genes and proteins in different cell lines and tissues. To assess the function of PIK3R3 and related mechanisms, the cells with RNAi-mediated knockdown or overexpression were used to perform a series of in vitro and in vivo assays. Results: PIK3R3 was significantly overexpressed in pancreatic cancer tissues, especially in metastatic cancer tissues, as well as in pancreatic cancer cells. Functional assays suggested that overexpression or knockdown of PIK3R3 could respectively promote or suppress the migration and invasion of PC cells in vitro and in vivo. Further mechanism related studies demonstrated that ERK1/2-ZEB1 pathway-triggered epithelial-mesenchymal transition (EMT) might be responsible for the PIK3R3-induced PC cell migration and invasion. Conclusion: PIK3R3 could promote the metastasis of PC by facilitating ZEB1 induced EMT, and could act as a potential therapeutic target to limit PC metastasis.

scholarly journals MiR-203a-3p Inhibits Pancreatic Cancer Cell Proliferation, EMT, and Apoptosis by Regulating SLUG

2020 ◽  
Vol 19 ◽  
pp. 153303381989872 ◽  
Author(s):  
Ning An ◽  
Bo Zheng
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Transition Process ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Messenger Rnas ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells ◽  
Cancer Tissues

Objective: The aim of the present research is to study the roles of miR-203a-3p on cell proliferation, migration, invasion, and epithelial–mesenchymal transition in pancreatic cancer. Methods: Transcription profiles were acquired from Gene Expression Omnibus database, which was used to screen out the differentially expressed microRNAs and messenger RNAs in pancreatic cancer. Pancreatic cancer tissues were used to verify the bioinformatics results by quantitative real-time polymerase chain reaction. The relationship between miR-203a-3p and SLUG was examined by TargetScan software, dual-luciferase reporter assay, and RNA immunoprecipitation. The Cell Counting Kit-8, wound healing, and transwell assays were conducted to investigate the proliferation, migration, and invasion capability of pancreatic cancer cells, respectively. The expression of epithelial–mesenchymal transition–related proteins was determined by the Western blot assay. Xenograft assay was performed to verify findings from in vitro assays. Results: Bioinformatic analysis found that a total of 113 microRNAs and 1749 messenger RNAs expressed differentially in pancreatic cancer tissues. Among these microRNAs, the expression of miR-203a-3p was significantly decreased in both pancreatic cancer tissues and cells. On the other hand, the SLUG expression was remarkably upregulated in pancreatic cancer tissues and cells in comparison with normal tissues and cells. Moreover, TargetScan software, dual-luciferase reporter assay, and RNA immunoprecipitation revealed that SLUG was a target of miR-203a-3p. The upregulation of miR-203a-3p expression inhibited the proliferation, migration, and invasion ability of pancreatic cancer cells by suppressing the epithelial–mesenchymal transition process via sponging SLUG. Conclusion: These findings indicate that downregulation of miR-203a-3p in pancreatic cancer cells leads to high expression of SLUG, which promotes epithelial–mesenchymal transition process and induces cancer progression.

scholarly journals N6-Methyladenosine Regulates the Expression and Secretion of TGFβ1 to Affect the Epithelial–Mesenchymal Transition of Cancer Cells

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 296 ◽  
Author(s):  
Jiexin Li ◽  
Feng Chen ◽  
Yanxi Peng ◽  
Ziyan Lv ◽  
Xinyao Lin ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Transforming Growth Factor Β ◽  
Dimer Formation ◽  
Mesenchymal Transition ◽  
Functional Roles ◽  
Key Factor ◽  
The Relationship

N6-methyladenosine (m6A) is the most abundant modification on eukaryotic mRNA, which regulates all steps of the mRNA life cycle. An increasing number of studies have shown that m6A methylation plays essential roles in tumor development. However, the relationship between m6A and the progression of cancers remains to be explored. Here, we reported that transforming growth factor-β (TGFβ1)-induced epithelial–mesenchymal transition (EMT) was inhibited in methyltransferase-like 3 (METTL3) knockdown (Mettl3Mut/−) cells. The expression of TGFβ1 was up-regulated, while self-stimulated expression of TGFβ1 was suppressed in Mettl3Mut/− cells. We further revealed that m6A promoted TGFB1 mRNA decay, but impaired TGFB1 translation progress. Besides this, the autocrine of TGFβ1 was disrupted in Mettl3Mut/− cells via interrupting TGFβ1 dimer formation. Lastly, we found that Snail, which was down-regulated in Mettl3Mut/− cells, was a key factor responding to TGFβ1-induced EMT. Together, our research demonstrated that m6A performed multi-functional roles in TGFβ1 expression and EMT modulation, suggesting the critical roles of m6A in cancer progression regulation.

scholarly journals LncRNA SNHG12 contributes proliferation, invasion and epithelial–mesenchymal transition of pancreatic cancer cells by absorbing miRNA-320b

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Wei Cao ◽  
Guoxiong Zhou
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Small Nuclear Rna ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells ◽  
Cancer Tissues ◽  
Western Blotting Assay ◽  
Proliferation And Invasion ◽  
Early Diagnostic

Abstract Pancreatic cancer is a kind of malignant carcinoma with high mortality, which is devoid of early diagnostic biomarker and effective therapeutic methods. Recently, long non-coding RNAs (lncRNAs) have been reported as a crucial role in regulating the development of various kinds of tumors. Here, we found lncRNA small nuclear RNA host gene 12 (SNHG12) is highly expressed in pancreatic cancer tissues and cell lines through qRT-PCR, which suggested that SNHG12 possibly accelerates the progression of pancreatic cancer. Further study revealed that SNHG12 promoted cancer cells growth and invasion via absorbing miR-320b. Flow cytometry and transwell chamber assay were utilized to verify the promoting effects on proliferation and invasion that SNHG12 acts in pancreatic cancer cells. Evidence that SNHG12 increased cell invasive ability through up-regulated EMT process was lately obtained by Western blotting assay. Consequently, we extrapolated that SNHG12/miR-320b could be invoked as a promising early diagnostic hallmark and therapeutic strategy for pancreatic cancer.

scholarly journals CircRNA circ_0092314 Induces Epithelial-Mesenchymal Transition of Pancreatic Cancer Cells via Elevating the Expression of S100P by Sponging miR-671

2021 ◽  
Vol 11 ◽  
Author(s):  
Qian Shen ◽  
Gang Zheng ◽  
Yi Zhou ◽  
Jin Tong ◽  
Sanpeng Xu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Downstream Target ◽  
Normal Tissues ◽  
Pancreatic Cancer Cells

BackgroundCircular RNAs (circRNAs) is a novel class of non-coding RNAs that regulate gene expression during cancer progression. Circ_0092314 is a newly discovered circRNA that was upregulated in pancreatic cancer (PAAD) tissues. However, the detailed functions and underlying mechanisms of circ_0092314 in PAAD cells remain unclear.MethodsWe first determined the expression of circ_0092314 in PAAD and normal tissues and further investigated the functional roles of circ_0092314 in regulating epithelial-mesenchymal transition (EMT) of PAAD cells. We also assessed the regulatory action of circ_0092314 on the microRNA-671 (miR-671) and its target S100P.ResultsCirc_0092314 was markedly upregulated in PAAD tissues and cells, and its overexpression was closely correlated with worse prognosis of PAAD patients. Functionally, circ_0092314 promotes proliferation, invasion and EMT in vitro and tumor growth in vivo. Mechanistically, we demonstrated that circ_0092314 directly binds to miR-671 and relieve its suppression of the downstream target S100P, which induces EMT and activates the AKT signaling pathway. The tumor-promoting effects caused by overexpression of circ_0092314 could be revered by re-expression of miR-671 in PAAD cells.ConclusionsOverall, our study demonstrates that circ_0092314 exerts critical roles in promoting the EMT features of PAAD cells, and provides insight into how elevated expression of circ_0092314 might influence PAAD progression.

scholarly journals αvβ3 Integrin induces partial EMT independent of TGF-β signaling

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yoshinobu Kariya ◽  
Midori Oyama ◽  
Takato Suzuki ◽  
Yukiko Kariya
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Αvβ3 Integrin ◽  
Poor Survival ◽  
Mesenchymal Transition ◽  
Intermediate States ◽  
Tgf Β1

AbstractEpithelial–mesenchymal transition (EMT) plays a pivotal role for tumor progression. Recent studies have revealed the existence of distinct intermediate states in EMT (partial EMT); however, the mechanisms underlying partial EMT are not fully understood. Here, we demonstrate that αvβ3 integrin induces partial EMT, which is characterized by acquiring mesenchymal phenotypes while retaining epithelial markers. We found αvβ3 integrin to be associated with poor survival in patients with lung adenocarcinoma. Moreover, αvβ3 integrin-induced partial EMT promoted migration, invasion, tumorigenesis, stemness, and metastasis of lung cancer cells in a TGF-β-independent fashion. Additionally, TGF-β1 promoted EMT progression synergistically with αvβ3 integrin, while a TGF-β signaling inhibitor showed no effect on αvβ3 integrin-induced partial EMT. Meanwhile, the microRNA-200 family abolished the αvβ3 integrin-induced partial EMT by suppressing αvβ3 integrin cell surface expression. These findings indicate that αvβ3 integrin is a key inducer of partial EMT, and highlight a new mechanism for cancer progression.

scholarly journals Long noncoding RNA LINC00941 promotes pancreatic cancer progression by competitively binding miR-335-5p to regulate ROCK1-mediated LIMK1/Cofilin-1 signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jie Wang ◽  
Zhiwei He ◽  
Jian Xu ◽  
Peng Chen ◽  
Jianxin Jiang
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Cell Lines ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Loss Of Function ◽  
Mesenchymal Transition

AbstractAn accumulation of evidence indicates that long noncoding RNAs are involved in the tumorigenesis and progression of pancreatic cancer (PC). In this study, we investigated the functions and molecular mechanism of action of LINC00941 in PC. Quantitative PCR was used to examine the expression of LINC00941 and miR-335-5p in PC tissues and cell lines, and to investigate the correlation between LINC00941 expression and clinicopathological features. Plasmid vectors or lentiviruses were used to manipulate the expression of LINC00941, miR-335-5p, and ROCK1 in PC cell lines. Gain or loss-of-function assays and mechanistic assays were employed to verify the roles of LINC00941, miR-335-5p, and ROCK1 in PC cell growth and metastasis, both in vivo and in vitro. LINC00941 and ROCK1 were found to be highly expressed in PC, while miR-335-5p exhibited low expression. High LINC00941 expression was strongly associated with larger tumor size, lymph node metastasis, and poor prognosis. Functional experiments revealed that LINC00941 silencing significantly suppressed PC cell growth, metastasis and epithelial–mesenchymal transition. LINC00941 functioned as a molecular sponge for miR-335-5p, and a competitive endogenous RNA (ceRNA) for ROCK1, promoting ROCK1 upregulation, and LIMK1/Cofilin-1 pathway activation. Our observations lead us to conclude that LINC00941 functions as an oncogene in PC progression, behaving as a ceRNA for miR-335-5p binding. LINC00941 may therefore have potential utility as a diagnostic and treatment target in this disease.

scholarly journals LncRNA-ZFAS1 Induces Epithelial-Mesenchymal Transition of Pancreatic Cancer Cells During Nutrient Deprivation by Promoting AMPK-Mediated Phosphorylation and Stabilization Of ZEB1 Protein

2021 ◽  
Author(s):  
ZHU ZENG ◽  
Shengbo Han ◽  
Yang Wang ◽  
Yan Huang ◽  
Yuhang Hu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Nutrient Deprivation ◽  
Loss Of Function ◽  
Western Blot Assay ◽  
Normal Medium ◽  
Mesenchymal Transition ◽  
Glucose Depletion ◽  
Pancreatic Cancer Cells ◽  
Glutamine Deprivation

Abstract Background: Nutrient deprivation is a distinct feature of the tumor microenvironment that plays a crucial role in various cancers. However, the contribution and regulatory mechanism of nutrient deprivation on metastasis of pancreatic cancer (PC) have not been identified. Methods: PC cells were treated with normal medium, glucose-depletion or glutamine-depletion medium to observe the epithelial-mesenchymal transition (EMT). RT-qPCR and western blot assay were applied to evaluate the alteration of mRNA and protein of zinc finger E-box binding homeobox 1 (ZEB1), a crucial EMT regulator factor. Co-IP assay was utilized for evaluating the interaction between AMP-activated protein kinase (AMPK) and ZEB1. LncRNA microarray was adopted to detect the potential lncRNA, which facilitates the association between AMPK and ZEB1. Gain- and loss-of-function experiments were performed to evaluate the roles of ZNFX1 antisense RNA 1 (ZFAS1) in EMT and metastasis of PC. Results: The present study reveals that nutrient deprivation including glucose and glutamine deprivation significantly induces EMT of PC cells, which is dependent on stabilization of ZEB1. We further discover that nutrient deprivation induces upregulation of lncRNA ZFAS1, which promotes the association between AMPK and ZEB1 to phosphorylate and stabilize ZEB1 protein. Notably, ZEB1 reciprocally promotes the transcription of ZFAS1 by binding to the promoter of ZFAS1, forming feedback with ZFAS1. Consistently, depletion of ZFAS1 obviously inhibits nutrient deprivation-induced EMT of PC cells and lung metastasis of PC in nude mice. Meanwhile, clinical data displays that ZFAS1 is overexpressed in PC tissues and correlated with high expression of ZEB1 and Vimentin (VIM), low expression of E-cadherin (E-cad), as well as poor prognosis in PC patients. Conclusions: Our study implicates that glucose and glutamine deprivation promotes EMT and metastasis of PC through lncRNA-mediated stabilization of ZEB1.

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