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 circPTPN12/miR-21–5 p/∆Np63α pathway contributes to human endometrial fibrosis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Minmin Song ◽  
Guangfeng Zhao ◽  
Haixiang Sun ◽  
Simin Yao ◽  
Zhenhua Zhou ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rnas ◽  
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-21–5 p to inhibit miR-21–5 p 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 and administration of miR-21–5 p could reverse this process and improve endometrial fibrosis. Our findings revealed that the dysfunction of circPTPN12/miR-21–5 p/∆Np63α pathway contributed to the pathogenesis of endometrial fibrosis.

scholarly journals The emerging role of circular RNAs in common solid malignant tumors in children

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiabin Yu ◽  
Li Yang ◽  
Hongting Lu
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Circular Rnas ◽  
Development Research ◽  
Physical And Mental Health ◽  
Invasive Ability ◽  
Mesenchymal Transition ◽  
Circular Structure ◽  
Solid Malignant Tumors

AbstractMalignant tumors are one of the fatal diseases that threaten children’s physical and mental health and affect their development. Research has shown that the occurrence and development of malignant tumors are associated with the abnormal expression and regulation of genes. Circular RNAs (circRNAs) are noncoding RNAs that have a closed circular structure, with a relatively stable expression, and do not undergo exonuclease-mediated degradation readily. Recent studies have shown that circRNA plays an important role in the occurrence, metastasis, and invasion of solid malignant tumors (SMTs) in children. Thus, circRNA is being considered as a breakthrough in the treatment of SMTs in children. In this review, we describe the functions and mechanisms of circRNAs involved in SMTs in children oncogenesis, and summarize the roles of circRNAs in regulating cell proliferation, cell apoptotic death, the cell cycle, cell migrative and invasive ability, epithelial-mesenchymal transition (EMT), cancer stem cells and drug resistance in SMTs in children. In addition, we also discuss the role of circRNAs in the early diagnosis, pathological grading, targeted therapy, and prognosis evaluation of common SMTs in children. CircRNAs are likely to provide a novel direction in therapy in SMTs of children.

scholarly journals Circ_001569 regulates FLOT2 expression to promote the proliferation, migration, invasion and EMT of osteosarcoma cells through sponging miR-185-5p

2020 ◽  
Vol 15 (1) ◽  
pp. 476-487
Author(s):  
Bin Xiao ◽  
Xusheng Zhang ◽  
Xiaojuan Li ◽  
Zhipeng Zhao
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
New Approach ◽  
Mesenchymal Transition ◽  
Proliferation And Metastasis ◽  
Related Proteins

AbstractOsteosarcoma (OS) is a common malignant tumor in the world. Circular RNAs are endogenous non-coding RNAs that have been linked to the development of cancer. However, the role of circ_001569 in OS progression is still unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_001569, microRNA-185-5p (miR-185-5p) and flotillin-2 (FLOT2). The abilities of cell proliferation, migration and invasion were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Transwell assays, respectively. Also, western blot analysis was performed to assess the levels of epithelial–mesenchymal transition (EMT)-related proteins and FLOT2 protein. Besides, the dual-luciferase reporter assay was used to verify the interactions among circ_001569, miR-185-5p and FLOT2. Circ_001569 expression was increased in OS tissues and cells, and its knockdown reduced the proliferation, migration, invasion and EMT of OS cells. MiR-185-5p could interact with circ_001569. Inhibition of miR-185-5p could recover the suppression effects of silenced-circ_001569 on the proliferation and metastasis of OS cells. Furthermore, FLOT2 was a target of miR-185-5p. Overexpressed FLOT2 could restore the inhibition effects of miR-185-5p mimic on the proliferation and metastasis of OS cells. Also, FLOT2 expression was regulated by circ_001569 and miR-185-5p. In addition, circ_001569 knockdown also reduced the OS tumor growth in vivo. Circ_001569 might act as an oncogene in OS progression by regulating the miR-185-5p/FLOT2 axis, which provided a reliable new approach for the treatment of OS patients.

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 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 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.

scholarly journals Prolonged Nitric Oxide Exposure Enhances Anoikis Resistance and Migration through Epithelial-Mesenchymal Transition and Caveolin-1 Upregulation

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Pithi Chanvorachote ◽  
Varisa Pongrakhananon ◽  
Preedakorn Chunhacha
Keyword(s):  
Nitric Oxide ◽  
Lung Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
The Novel ◽  
Anoikis Resistance ◽  
Mesenchymal Transition ◽  
Caveolin 1 ◽  
And Migration

Nitric oxide (NO) in tumor microenvironment may have a significant impact on metastatic behaviors of cancer. Noncytotoxic doses of NO enhanced anoikis resistance and migration in lung cancer H23 cells via an increase in lamellipodia, epithelial-mesenchymal transition (EMT) markers including vimentin and snail, and caveolin-1 (Cav-1). However, the induction of EMT was found in Cav-1-knock down cells treated with NO, suggesting that EMT was through Cav-1-independent pathway. These effects of NO were consistently observed in other lung cancer cells including H292 and H460 cells. These findings highlight the novel role of NO on EMT and metastatic behaviors of cancer cells.

scholarly journals Subcellular Expression of Maspin in Colorectal Cancer: Friend or Foe

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 366
Author(s):  
Simona Gurzu ◽  
Ioan Jung
Keyword(s):  
Therapeutic Strategy ◽  
Epithelial Mesenchymal Transition ◽  
Molecular Data ◽  
Daily Experience ◽  
Mesenchymal Transition ◽  
Bowel Diseases ◽  
Maspin Expression ◽  
Inflammatory Bowel ◽  
Original Observation

In this review the authors aimed to emphasize the practical value of nuclear expression of the mammary serine protease inhibitor (maspin), also known as serpin B5 protein, in colorectal carcinoma (CRC), from pre-malignant disorders to carcinogenesis and metastasis. As the role of maspin is controversial and not yet understood, the present update highlights the latest data revealed by literature which were filtrated through the daily experience of the authors, which was gained at microscopic examination of maspin expression in CRCs and other tumors for daily diagnosis. Data regarding the subcellular localization of maspin, in correlation with the microsatellite status, grade of tumor dedifferentiation, and epithelial-mesenchymal transition (EMT) phenomenon of the tumor buds were presented with details. An original observation refers to the maspin capacity to mark the tumor cells which are “at the point of budding” that were previously considered as having “hybrid EMT phenotype”. It refers to the transitional status of tumor cell that is between “epithelial status” and “mesenchymal status”. The second original hypothesis highlights the possible role of maspin in dysregulating the intestinal microbiota, in patients with idiopathic inflammatory bowel diseases (IBD) and inducing IBD-related CRC. The dynamic process of budding and EMT of tumor buds, possible mediated by maspin, needs further investigation and validation in many human CRC samples. The histological and molecular data reveal that synthesis of maspin-based therapeutics might represent a novel individualized therapeutic strategy for patients with CRC.

scholarly journals Circ_0000658 knockdown inhibits epithelial-mesenchymal transition in bladder cancer via miR-498-induced HMGA2 downregulation

2022 ◽  
Vol 41 (1) ◽  
Author(s):  
Feng Qiu ◽  
Qiuchen Liu ◽  
Yanfu Xia ◽  
Hengxi Jin ◽  
Yuxin Lin ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Growth ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Circular Rnas ◽  
Tissue Samples ◽  
Mesenchymal Transition

Abstract Background Epithelial-mesenchymal transition (EMT) has been associated with the angiogenesis and oncogenic phenotypes of multiple malignant tumors including bladder cancer (BCa). Circular RNAs (circRNAs) are recognized as crucial regulators in the EMT. This study aims to illustrate the possible role of circular RNA_0000658 (circ_0000658) in BCa and the underlying molecular mechanism. Methods The expression of circ_0000658, microRNA (miR)-498, and high mobility group AT-hook 2 (HMGA2) was assessed in cancer and adjacent normal tissue collected from BCa patients and human BCa cell lines (MGH-U3, T24, 5637 and SW780). BCa cells were transduced with a series of overexpression or shRNA plasmids to clarify the function of circ_0000658 and miR-498 on the oncogenic phenotypes and EMT of BCa cells. Further, we established nude mice xenografted with BCa cells to validate the roles of circ_0000658 on tumor growth in vivo. Results Circ_0000658 was highly expressed in BCa tissue samples and cell lines, which indicated a poor prognosis of BCa patients. Circ_0000658 competitively bound to miR-498 and thus restricted miR-498 expression. Meanwhile, circ_0000658 weakened the binding of miR-498 to the target gene HMGA2 and upregulated the HMGA2 expression. Circ_0000658 elevation or miR-498 knockdown augmented oncogenic phenotypes and EMT of BCa cells, corresponding to a reduction in the expression of β-catenin and E-cadherin as well as an increase in the expression of N-cadherin, Slug, Snail, ZEB1 and Twist. Inhibition of HMGA2 reversed the effects of circ_0000658 overexpression on tumor growth in vivo. Conclusion Altogether, our study uncovered the tumor-promoting role of circ_0000658 in BCa via the miR-498/HMGA2 axis.

Magnesium Chloride is an Effective Therapeutic Agent for Prostate Cancer

2018 ◽  
Vol 8 (1) ◽  
pp. 62 ◽  
Author(s):  
Julianna Maria Santos ◽  
Fazle Hussain
Keyword(s):  
Prostate Cancer ◽  
Magnesium Chloride ◽  
Epithelial Mesenchymal Transition ◽  
Chromatin Condensation ◽  
Myosin Ii ◽  
In Vivo Studies ◽  
Migration Speed ◽  
Mesenchymal Transition

Background: Reduced levels of magnesium can cause several diseases and increase cancer risk. Motivated by magnesium chloride’s (MgCl2) non-toxicity, physiological importance, and beneficial clinical applications, we studied its action mechanism and possible mechanical, molecular, and physiological effects in prostate cancer with different metastatic potentials.Methods: We examined the effects of MgCl2, after 24 and 48 hours, on apoptosis, cell migration, expression of epithelial mesenchymal transition (EMT) markers, and V-H+-ATPase, myosin II (NMII) and the transcription factor NF Kappa B (NFkB) expressions.Results: MgCl2 induces apoptosis, and significantly decreases migration speed in cancer cells with different metastatic potentials.  MgCl2 reduces the expression of V-H+-ATPase and myosin II that facilitates invasion and metastasis, suppresses the expression of vimentin and increases expression of E-cadherin, suggesting a role of MgCl2 in reversing the EMT. MgCl2 also significantly increases the chromatin condensation and decreases NFkB expression.Conclusions: These results suggest a promising preventive and therapeutic role of MgCl2 for prostate cancer. Further studies should explore extending MgCl2 therapy to in vivo studies and other cancer types.Keywords: Magnesium chloride, prostate cancer, migration speed, V-H+-ATPase, and EMT.

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