scholarly journals Sexual Dimorphism in Colon Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Maria Abancens ◽  
Viviana Bustos ◽  
Harry Harvey ◽  
Jean McBryan ◽  
Brian J. Harvey
Keyword(s):  
Sexual Dimorphism ◽  
Older Women ◽  
Epithelial Mesenchymal Transition ◽  
Protective Role ◽  
Survival Outcome ◽  
The Novel ◽  
Sex Steroid Hormone ◽  
Mesenchymal Transition ◽  
Vegf Signaling ◽  
Kv Channels

A higher incidence of colorectal cancer (CRC) is found in males compared to females. Young women (18–44 years) with CRC have a better survival outcome compared to men of the same age or compared to older women (over 50 years), indicating a global incidence of sexual dimorphism in CRC rates and survival. This suggests a protective role for the sex steroid hormone estrogen in CRC development. Key proliferative pathways in CRC tumorigenesis exhibit sexual dimorphism, which confer better survival in females through estrogen regulated genes and cell signaling. Estrogen regulates the activity of a class of Kv channels (KCNQ1:KCNE3), which control fundamental ion transport functions of the colon and epithelial mesenchymal transition through bi-directional interactions with the Wnt/β-catenin signalling pathway. Estrogen also modulates CRC proliferative responses in hypoxia via the novel membrane estrogen receptor GPER and HIF1A and VEGF signaling. Here we critically review recent clinical and molecular insights into sexual dimorphism of CRC biology modulated by the tumor microenvironment, estrogen, Wnt/β-catenin signalling, ion channels, and X-linked genes.

scholarly journals Targeting circPTPN12/1 miR-21-5p/ΔNp63α pathway as a therapeutic strategy for human endometrial fibrosis

2021 ◽  
Author(s):  
Minmin Song ◽  
Guangfeng Zhao ◽  
Haixiang Sun ◽  
Simin Yao ◽  
Zhenhua Zhou ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rnas ◽  
The Novel ◽  
Mesenchymal Transition ◽  
Organ Fibrosis ◽  
Endometrial Epithelial Cells ◽  
Expression And Activity ◽  
Uterine Infertility

Emerging evidence demonstrates the important role of circular RNAs (circRNAs) in regulating pathological processes in various diseases including organ fibrosis. Endometrium fibrosis is the leading cause of uterine infertility, but the role of circRNAs in its pathogenesis is largely unknown. Here, we provide the evidence that upregulation of circPTPN12 in endometrial epithelial cells (EECs) of fibrotic endometrium functions as endogenous sponge of miR-21-5p to inhibit miR-21-5p expression and activity, which in turn results in upregulation of ΔNp63α to induce the epithelial mesenchymal transition (EMT) of EECs (EEC-EMT). In a mouse model of endometrium fibrosis, circPTPN12 appears to be a cofactor of driving EEC-EMT. Our findings reveal the novel mechanism in the pathogenesis of endometrium fibrosis and the potential therapeutic strategy for endometrium fibrosis via targeting circPTPN12/miR-21-5p/∆Np63α pathway.

scholarly journals CircRTN4 promotes pancreatic cancer progression through a novel CircRNA-miRNA-lncRNA pathway and stabilizing epithelial-mesenchymal transition protein

2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Chi Hin Wong ◽  
Ut Kei Lou ◽  
Frederic Khe-Cheong Fung ◽  
Joanna H. M. Tong ◽  
Chang-hua Zhang ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Tumor Growth ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Assay ◽  
Dimensional Structure ◽  
Mouse Tumor ◽  
The Novel ◽  
Primary Tumors ◽  
Mesenchymal Transition

Abstract Background Circular RNAs (circRNAs) play important roles in many biological processes. However, the detailed mechanism underlying the critical roles of circRNAs in cancer remains largely unexplored. We aim to explore the molecular mechanisms of circRTN4 with critical roles in pancreatic ductal adenocarcinoma (PDAC). Methods CircRTN4 expression level was examined in PDAC primary tumors. The oncogenic roles of circRTN4 in PDAC tumor growth and metastasis were studied in mouse tumor models. Bioinformatics analysis, luciferase assay and miRNA pulldown assay were performed to study the novel circRTN4-miRNA-lncRNA pathway. To identify circRTN4-interacting proteins, we performed circRNA-pulldown and mass spectrometry in PDAC cells. Protein stability assay and 3-Dimensional structure modeling were performed to reveal the role of circRTN4 in stabilizing RAB11FIP1. Results CircRTN4 was significantly upregulated in primary tumors from PDAC patients. In vitro and in vivo functional studies revealed that circRTN4 promoted PDAC tumor growth and liver metastasis. Mechanistically, circRTN4 interacted with tumor suppressor miR-497-5p in PDAC cells. CircRTN4 knockdown upregulated miR-497-5p to inhibit the oncogenic lncRNA HOTTIP expression. Furthermore, we identified critical circRTN4-intercting proteins by circRNA-pulldown in PDAC cells. CircRTN4 interacted with important epithelial-mesenchymal transition (EMT)- driver RAB11FIP1 to block its ubiquitination site. We found that circRTN4 knockdown promoted the degradation of RAB11FIP1 by increasing its ubiquitination. Also, circRTN4 knockdown inhibited the expression of RAB11FIP1-regulating EMT-markers Slug, Snai1, Twist, Zeb1 and N-cadherin in PDAC. Conclusion The upregulated circRTN4 promotes tumor growth and liver metastasis in PDAC through the novel circRTN4-miR-497-5p-HOTTIP pathway. Also, circRTN4 stabilizes RAB11FIP1 to contribute EMT. Graphical abstract

scholarly journals Potential Anti-Metastatic Role of the Novel miR-CT3 in Tumor Angiogenesis and Osteosarcoma Invasion

2022 ◽  
Vol 23 (2) ◽  
pp. 705
Author(s):  
Lavinia Raimondi ◽  
Alessia Gallo ◽  
Nicola Cuscino ◽  
Angela De Luca ◽  
Viviana Costa ◽  
...  
Keyword(s):  
Tumor Angiogenesis ◽  
Epithelial Mesenchymal Transition ◽  
P38 Map Kinase ◽  
Luciferase Assay ◽  
Molecular Profile ◽  
Migration And Invasion ◽  
The Novel ◽  
Vimentin Expression ◽  
Mesenchymal Transition

Osteosarcoma (OS) is the most common primary bone tumor mainly occurring in young adults and derived from primitive bone-forming mesenchyme. OS develops in an intricate tumor microenvironment (TME) where cellular function regulated by microRNAs (miRNAs) may affect communication between OS cells and the surrounding TME. Therefore, miRNAs are considered potential therapeutic targets in cancer and one of the goals of research is to accurately define a specific signature of a miRNAs, which could reflect the phenotype of a particular tumor, such as OS. Through NGS approach, we previously found a specific molecular profile of miRNAs in OS and discovered 8 novel miRNAs. Among these, we deepen our knowledge on the fifth candidate renamed now miR-CT3. MiR-CT3 expression was low in OS cells when compared with human primary osteoblasts and healthy bone. Through TargetScan, VEGF-A was predicted as a potential biological target of miR-CT3 and luciferase assay confirmed it. We showed that enforced expression of miR-CT3 in two OS cell lines, SAOS-2 and MG-63, reduced expression of VEGF-A mRNA and protein, inhibiting tumor angiogenesis. Enforced expression of miR-CT3 also reduced OS cell migration and invasion as confirmed by soft agar colony formation assay. Interestingly, we found that miR-CT3 behaves inducing the activation of p38 MAP kinase pathway and modulating the epithelial-mesenchymal transition (EMT) proteins, in particular reducing Vimentin expression. Overall, our study highlights the novel role of miR-CT3 in regulating tumor angiogenesis and progression in OS cells, linking also to the modulation of EMT proteins.

scholarly journals Protective Role of Bokusoku in Dextran Sulphate Sodium Induced Colitis via Inhibition of Epithelial-mesenchymal Transition

2018 ◽  
Vol 44 (3) ◽  
pp. 117-127
Author(s):  
Shizuka Miyashita ◽  
Remya Sreedhar ◽  
Somasundaram Arumugam ◽  
Vengadeshprabhu Karuppagounder ◽  
Hiroshi Suzuki ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Protective Role ◽  
Dextran Sulphate ◽  
Dextran Sulphate Sodium ◽  
Mesenchymal Transition

scholarly journals Exosomal miRNA-215-5p Derived from Adipose-Derived Stem Cells Attenuates Epithelial–Mesenchymal Transition of Podocytes by Inhibiting ZEB2

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Juan Jin ◽  
Yunguang Wang ◽  
Li Zhao ◽  
Wenli Zou ◽  
Mingming Tan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Viability ◽  
Epithelial Mesenchymal Transition ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Luciferase Reporter ◽  
Adipose Derived Stem Cells ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
And Migration

Background. Podocyte migration is actively involved in the process of podocyte loss and proteinuria production, which is closely associated with the development of diabetic nephropathy (DN). Exosomes from adipose-derived stem cells (ADSCs-Exos) effectively inhibit podocyte apoptosis in the treatment of DN. However, how ADSCs-Exos affect the migration of podocytes is obscure. This study is aimed at exploring the regulatory role of ADSCs-Exos on cell migration and the underlying mechanism. Methods. ADSCs-Exo was authenticated by transmission electron microscopy (TEM), western blotting, and flow cytometry. Cell viability and migration ability of podocytes were measured by CCK8 and Transwell assays, respectively. Relative expressions of miRNAs and mRNAs were determined by qRT-PCR. The transmitting between PKH26-labeled exosome and podocytes was evaluated by IF assay. Dual luciferase reporter assay was employed to detect the relationship between miR-215-5p and ZEB2. Results. The exposure to serum from DN patient (hDN-serum) significantly inhibited cell viability of podocytes, but ADSCs-Exo addition notably blunts cytotoxicity induced by the transient stimulus of hDN-serum. Besides, ADSCs-Exo administration powerfully impeded high glucose- (HG-) induced migration and injury of podocyte. With the podocyte dysfunction, several miRNAs presented a significant decline under the treatment of HG including miR-251-5p, miR-879-5p, miR-3066-5p, and miR-7a-5p, all of which were rescued by the addition of ADSCs-Exo. However, only miR-251-5p was a key determinant in the process of ADSCs-Exo-mediated protective role on podocyte damage. The miR-251-5p inhibitor counteracted the improvement from the ADSCs-Exo preparation on HG-induced proliferation inhibition and migration promotion. Additionally, miR-215-5p mimics alone remarkably reversed HG-induced EMT process of podocyte. Mechanistically, we confirmed that ADSCs-Exos mediated the shuttling of miR-215-5p to podocyte, thereby protecting against HG-induced metastasis, possibly through inhibiting the transcription of ZEB2. Conclusion. ADSCs-Exo has the protective effect on HG-evoked EMT progression of podocytes thru a mechanism involving ZEB2. Potentially, the ADSCs-Exo preparation is a useful therapeutic strategy for improving podocyte dysfunction and DN symptoms clinically.

scholarly journals MiR-30c-5p/ROCK2 axis regulates cell proliferation, apoptosis and EMT via the PI3K/AKT signaling pathway in HG-induced HK-2 cells

2020 ◽  
Vol 15 (1) ◽  
pp. 959-970
Author(s):  
Lianshun Cui ◽  
Meiyan Yu ◽  
Xinglei Cui
Keyword(s):  
Cell Proliferation ◽  
Target Gene ◽  
Epithelial Mesenchymal Transition ◽  
Akt Signaling ◽  
Akt Pathway ◽  
The Novel ◽  
Akt Signaling Pathway ◽  
Mesenchymal Transition

AbstractDiabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. Increasing evidence suggests that microRNA-30c-5p (miR-30c-5p) participates in the pathogenesis of DN, but the mechanism has not been clearly understood. Therefore, this study aimed to investigate the biological role of miR-30c-5p in human DN progression in vitro. Compared with the controls, DN tissues and high glucose-induced HK-2 cells had significantly reduced miR-30c-5p levels, while ROCK2 expression was prominently elevated. Additionally, the miR-30c-5p mimic distinctly facilitated cell proliferation and blocked cell apoptosis and epithelial–mesenchymal transition (EMT). However, ROCK2 was a target gene of miR-30c-5p, and the effects of miR-30c-5p mimic on cell proliferation, apoptosis and EMT were reversed by ROCK2 upregulation in vitro. Furthermore, the pathogenesis of DN was regulated by the miR-30c-5p/ROCK2 axis via the PI3K/AKT pathway. MiR-30c-5p regulating cell proliferation, apoptosis and EMT through targeting ROCK2 via the PI3K/AKT pathway provides the novel potential target for clinical treatment of DN.

Exposure to desflurane anesthesia confers colorectal cancer cells metastatic capacity through deregulation of miR-34a/LOXL3 

2020 ◽  
Author(s):  
Junyi Ren ◽  
Xiaopeng Wang ◽  
Gang Wei ◽  
Yajing Meng
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Protective Role ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Elevated Expression ◽  
Public Datasets

Abstract Background: Due to high potency and low toxicity, desflurane has been wildly used during surgery. Recent evidence that the use of desflurane was associated with colorectal cancer (CRC) tumor metastasis and poor prognosis raising concerns about the safety of desflurane. However, the mechanism was uncovered.Methods: CRC cells were exposed to desflurane, the changes in morphology and epithelial-mesenchymal transition (EMT)-related genes were evaluated. Transwell assay was used to study the migration and invasion effect. Xenograft was performed to study the tumor formation ability of desflurane-treated cells in vivo. Dual luciferase reporter assay was conducted to verify the target of miR-34a. Knockdown or overexpression of LOXL3 was used to investigate the mechanism of desflurane-induced EMT. The association of LOXL3 with CRC molecular subtypes and clinical relevance was studied by analysis of public datasets. Results: Exposure to desflurane induced EMT, migration, and invasion in CRC cells. Mice injected with desflurane-treated cells formed more tumors in the lungs. Downregulation of miR-34a and upregulation of LOXL3 were required for desflurane-induced EMT in CRC cells. LOXL3 was a direct target of miR-34a. Overexpression of LOXL3 rescued miR-34a-repressed EMT after exposure to desflurane. Elevated expression of LOXL3 was enriched in CMS4 and CRIS-B subtypes. Patients with high expression of LOXL3 showed more lymph node metastasis, as well as poor survival.Conclusion: Desflurane induced EMT and metastasis in CRC through deregulation of miR-34a/LOXL3 axis. Clinical miR-34a mimic or inhibitor targeting LOXL3 might have a potential protective role when CRC patients anesthetized by desflurane.

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