Microarray to reveal LncRNA profile and the role of lncCUEDC1 in BCSCs.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 3-3
Author(s):  
Fengchun Zhang ◽  
Ying chun Xu ◽  
Ning Yan
Keyword(s):  
Breast Cancer ◽  
Cultured Cells ◽  
Bioinformatics Analyses ◽  
Functional Roles ◽  
Functional Activities ◽  
Non Coding Rnas ◽  
Microarray Analyses ◽  
First Time

3 Background: Recently, a growing amount of reports have shown that long non-coding RNAs (lncRNAs) are involved in breast cancer development, progression and metastasis. However, the correlation between lncRNAs and breast cancer stem cells (BCSCs) has been poorly explored. Methods: We initially isolated BCSCs from mammosphere-cultured cells; then, microarray analyses were carried out to detect the lncRNA signature in BCSCs. In addition, bioinformatics analyses, including Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), were consulted to explore the functional roles of lncRNAs on BCSCs. Results: A total of 142 aberrantly expressed lncRNAs in BCSCs were identified, and of those lncRNAs, 25 were downregulated and 117 were upregulated compared to non-BCSCs. In addition, some of these lncRNAs were randomly selected and verified by RT-PCR and sanger sequencing. Notably, bioinformatics data showed that the lncRNAs that were detected were largely associated with stemness-related signalling pathways. Additionally, an interacting network between lncRNAs and its mRNAs was constructed to further depict the lncRNA functional activities. Furthermore, we found that lncCUEDC1 negatively regulated phenotype and biological functions of BCSCs in vitro. Conclusions: Our work establishes the lncRNAs signature in BCSCs for the first time. These findings provide us with evidence to explore the functionalities of lncRNAs in BCSCs and indicate that lncCUED1 is a prospective target for BCSCs.

scholarly journals Comprehensive Analysis of Aberrantly Expressed Profiles of ncRNAs Revealed lncRNA AGPAT4-IT1 is a Potential Prognostic Marker for Breast Cancer Metastasis

2020 ◽  
Author(s):  
Feng chun Zhang ◽  
ning ning yan ◽  
Ming jun Li ◽  
Ying chun Xu ◽  
Xing ya Li
Keyword(s):  
Breast Cancer ◽  
Prognostic Marker ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Bioinformatics Analyses ◽  
Functional Roles ◽  
Kaplan Meier ◽  
Non Coding Rnas ◽  
Microarray Analyses ◽  
The Relationship

Abstract Aims: we investigated the relationship between long non-coding RNAs (lncRNAs) and breast cancer lung metastasis (BCLM). Methods: We performed lncRNA microarray analyses to establish the lncRNA profile of BCLM. Bioinformatics analyses were carried out to analyzed functional roles of identified lncRNAs. Kaplan-meier analysis was conducted to determine the relation between lncRNA AGPAT4-IT1 and prognosis of breast cancer. Results: We found 317 upregulated and 166 downregulated lncRNAs in BCLM group. We showed AGPAT4-IT1 was positively correlated with its parental gene APGAT4. Furthermore, we suggested AGPAT4-IT1 were highly expressed in higher tumour grade and predicted poorer prognosis. Conclusions: These findings provide evidence for exploring the mechanisms of BCLM and indicate AGPAT4-IT1 is a prospective prognostic marker for breast cancer metastasis.

scholarly journals Oncogenic UBE3C promotes breast cancer progression by activating Wnt/β-catenin signaling

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chen Hang ◽  
Shanojie Zhao ◽  
Tiejun Wang ◽  
Yan Zhang
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Nuclear Accumulation ◽  
Migration And Invasion ◽  
Ubiquitin Protein Ligase ◽  
Novel Target ◽  
First Time ◽  
Breast Tissues

Abstract Background Breast cancer (BrCa) is the most common female malignancy worldwide and has the highest morbidity among all cancers in females. Unfortunately, the mechanisms of BrCa growth and metastasis, which lead to a poor prognosis in BrCa patients, have not been well characterized. Methods Immunohistochemistry (IHC) was performed on a BrCa tissue microarray (TMA) containing 80 samples to evaluate ubiquitin protein ligase E3C (UBE3C) expression. In addition, a series of cellular experiments were conducted to reveal the role of UBE3C in BrCa. Results In this research, we identified UBE3C as an oncogenic factor in BrCa growth and metastasis for the first time. UBE3C expression was upregulated in BrCa tissues compared with adjacent breast tissues. BrCa patients with high nuclear UBE3C expression in tumors showed remarkably worse overall survival (OS) than those with low nuclear expression. Knockdown of UBE3C expression in MCF-7 and MDA-MB-453 BrCa cells inhibited cell proliferation, migration and invasion in vitro, while overexpression of UBE3C in these cells exerted the opposite effects. Moreover, UBE3C promoted β-catenin nuclear accumulation, leading to the activation of the Wnt/β-catenin signaling pathway in BrCa cells. Conclusion Collectively, these results imply that UBE3C plays crucial roles in BrCa development and progression and that UBE3C may be a novel target for the prevention and treatment of BrCa.

scholarly journals Transcriptomic Analysis of mRNA-lncRNA-miRNA Interactions in Hepatocellular Carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Xia Tang ◽  
Delong Feng ◽  
Min Li ◽  
Jinxue Zhou ◽  
Xiaoyuan Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Rna Seq ◽  
Pairwise Interactions ◽  
Micro Rnas ◽  
Non Coding Rnas ◽  
First Time

Abstract Fully elucidating the molecular mechanisms of non-coding RNAs (ncRNAs), including micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs), underlying hepatocarcinogenesis is challenging. We characterized the expression profiles of ncRNAs and constructed a regulatory mRNA-lncRNA-miRNA (MLMI) network based on transcriptome sequencing (RNA-seq) of hepatocellular carcinoma (HCC, n = 9) patients. Of the identified miRNAs (n = 203) and lncRNAs (n = 1,090), we found 16 significantly differentially expressed (DE) miRNAs and three DE lncRNAs. The DE RNAs were highly enriched in 21 functional pathways implicated in HCC (p < 0.05), including p53, MAPK, and NAFLD signaling. Potential pairwise interactions between DE ncRNAs and mRNAs were fully characterized using in silico prediction and experimentally-validated evidence. We for the first time constructed a MLMI network of reciprocal interactions for 16 miRNAs, three lncRNAs, and 253 mRNAs in HCC. The predominant role of MEG3 in the MLMI network was validated by its overexpression in vitro that the expression levels of a proportion of MEG3-targeted miRNAs and mRNAs was changed significantly. Our results suggested that the comprehensive MLMI network synergistically modulated carcinogenesis, and the crosstalk of the network provides a new avenue to accurately describe the molecular mechanisms of hepatocarcinogenesis.

scholarly journals Osthole Inhibits Breast Cancer Progression through Upregulating Tumor Suppressor GNG7

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jie Mei ◽  
Tiejun Wang ◽  
Shaojie Zhao ◽  
Yan Zhang
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Cancer Progression ◽  
Suppressive Effect ◽  
Normal Breast ◽  
Bioinformatics Analyses ◽  
Novel Target ◽  
The Relationship

Osthole (OST) is a plant-derived compound that can inhibit the proliferation of tumor cells and has a tumor-suppressive effect in multiple types of cancers. However, the mechanisms of OST-mediated breast cancer (BrCa) inhibition were still largely unknown. In this study, we made full use of the GSE85871 dataset to identify potential targets of OST in BrCa via multiple bioinformatics analysis. Next, a series of in vitro experiments were conducted to check the role of GNG7 in BrCa and the relationship between OST and GNG7. Through a series of bioinformatics analyses, GNG7 was identified as a potential target of OST, which could be significant upregulated by OST exposure in BrCa cells. Besides, GNG7 was lowly expressed in BrCa tissues compared with normal breast tissues, and BrCa patients with low GNG7 expression had shorter overall survival (OS) and relapse-free survival (RFS) compared with those with high GNG7 expression. Moreover, GNG7 silencing significantly enhanced cell proliferation and inhibited apoptosis, and exogenous overexpression of GNG7 showed reverse effects on BrCa cells. Last but not least, GNG7 inhibition could notably rescue OST-mediated cytotoxic effects. In summary, we identified GNG7 as a novel target for OST in BrCa and a potential tumor suppressor. Thus, OST could be therapeutically beneficial for BrCa through a GNG7-dependent mechanism.

scholarly journals LOC101930370/MiR-1471 Axis Modulates the Hedgehog Signaling Pathway in Breast Cancer

2018 ◽  
Vol 48 (3) ◽  
pp. 1139-1150 ◽  
Author(s):  
Xin Liu ◽  
Tong Zhao ◽  
Xue Bai ◽  
Mingqi Li ◽  
Jingli Ren ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hedgehog Signaling ◽  
Luciferase Assay ◽  
Loss Of Function ◽  
Functional Roles ◽  
Proliferation And Metastasis ◽  
Non Coding Rnas ◽  
Gli 1 ◽  
First Time ◽  
Mcf 7

Background/Aims: Non-coding RNAs (ncRNAs) play vital regulatory roles in many tumors. However, the functional roles of these transcripts responsible for their dysregulation in breast cancer (BC) are not thoroughly understood. Methods: We examined the expression of microRNA miR-1471 in BC specimens. Online analysis tools predicted that lncRNA LOC101930370 might act as an endogenous ‘sponge’ by competing for miR-1471 binding targets. Luciferase assays were used to prove the interaction of LOC101930370, miR-1471 and SHH. Edu, wound-healing and transwell assays were used to verify the contribution of miR-1471 and LOC101930370 on MCF-7 cells proliferation and metastasis. Gain and loss of function studies were performed to evaluate the relevance of Hedgehog pathway with LOC101930370/miR-1471 regulating axis in MCF-7 cells. Results: The expression of miR-1471 was markedly downregulated in BC. Inhibition of miR-1471 by LOC101930370 was proved by luciferase assay. Knockdown of LOC101930370 suppressed BC cells progression. MiR-1471 inhibitor resulted in a more aggressive metastasis of MCF-7 cells. Moreover, SHH and Gli-1 expression were significantly suppressed by LOC101930370 knockdown, and upregulated by miR-1471 inhibitor transfection. Conclusions: Collectively, our study reveals the interaction between LOC101930370 and miR-1471 for the first time. LOC101930370 positively regulates the expression of SHH by sponging miR-1471, which sheds new light on lncRNA-directed diagnostics and therapeutics in BC.

MicroRNAs as Biomarker for Breast Cancer

2020 ◽  
Vol 20 (10) ◽  
pp. 1597-1610 ◽  
Author(s):  
Taru Aggarwal ◽  
Ridhima Wadhwa ◽  
Riya Gupta ◽  
Keshav Raj Paudel ◽  
Trudi Collet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Association Studies ◽  
Large Family ◽  
Breast Cancer Diagnosis ◽  
Cell Multiplication ◽  
Cell Physiology ◽  
Gene Transcript ◽  
Genome Wide Association Studies ◽  
Non Coding Rnas

Regardless of advances in detection and treatment, breast cancer affects about 1.5 million women all over the world. Since the last decade, genome-wide association studies (GWAS) have been extensively conducted for breast cancer to define the role of miRNA as a tool for diagnosis, prognosis and therapeutics. MicroRNAs are small, non-coding RNAs that are associated with the regulation of key cellular processes such as cell multiplication, differentiation, and death. They cause a disturbance in the cell physiology by interfering directly with the translation and stability of a targeted gene transcript. MicroRNAs (miRNAs) constitute a large family of non-coding RNAs, which regulate target gene expression and protein levels that affect several human diseases and are suggested as the novel markers or therapeutic targets, including breast cancer. MicroRNA (miRNA) alterations are not only associated with metastasis, tumor genesis but also used as biomarkers for breast cancer diagnosis or prognosis. These are explained in detail in the following review. This review will also provide an impetus to study the role of microRNAs in breast cancer.

Let-7e-5p Regulates GLP-1 Content and Basal Release From Enteroendocrine L Cells From DIO Male Mice

Endocrinology ◽  
2019 ◽  
Vol 161 (2) ◽  
Author(s):  
Sandra Handgraaf ◽  
Rodolphe Dusaulcy ◽  
Florian Visentin ◽  
Jacques Philippe ◽  
Yvan Gosmain
Keyword(s):  
Compensatory Mechanism ◽  
L Cells ◽  
Low Fat Diet ◽  
Obesity And Diabetes ◽  
Basal Release ◽  
Glucagon Like Peptide 1 ◽  
Cell Transcriptome ◽  
Microarray Analyses

Abstract Characterization of enteroendocrine L cells in diabetes is critical for better understanding of the role of glucagon-like peptide-1 (GLP-1) in physiology and diabetes. We studied L-cell transcriptome changes including microRNA (miRNA) dysregulation in obesity and diabetes. We evaluated the regulation of miRNAs through microarray analyses on sorted enteroendocrine L cells from control and obese glucose-intolerant (I-HFD) and hyperglycemic (H-HFD) mice after 16 weeks of respectively low-fat diet (LFD) or high-fat diet (HFD) feeding. The identified altered miRNAs were studied in vitro using the mouse GLUTag cell line to investigate their regulation and potential biological functions. We identified that let-7e-5p, miR-126a-3p, and miR-125a-5p were differentially regulated in L cells of obese HFD mice compared with control LFD mice. While downregulation of let-7e-5p expression was observed in both I-HFD and H-HFD mice, levels of miR-126a-3p increased and of miR-125a-5p decreased significantly only in I-HFD mice compared with controls. Using miRNA inhibitors and mimics we observed that modulation of let-7e-5p expression affected specifically GLP-1 cellular content and basal release, whereas Gcg gene expression and acute GLP-1 secretion and cell proliferation were not affected. In addition, palmitate treatment resulted in a decrease of let-7e-5p expression along with an increase in GLP-1 content and release, suggesting that palmitate acts on GLP-1 through let-7e-5p. By contrast, modulation of miR-125a-5p and miR-126a-3p in the same conditions did not affect content or secretion of GLP-1. We conclude that decrease of let-7e-5p expression in response to palmitate may constitute a compensatory mechanism contributing to maintaining constant glycemia in obese mice.

scholarly journals Hsa_circ_0005273 facilitates breast cancer tumorigenesis by regulating YAP1-hippo signaling pathway

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Xuehui Wang ◽  
Changle Ji ◽  
Jiashu Hu ◽  
Xiaochong Deng ◽  
Wenfang Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Potential Biomarker

Abstract Background Circular RNAs (circRNAs), a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC). Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functional role of hsa_circ_0005273 in BC remains largely unknown. Here we aim to evaluate the role of hsa_circ_0005273 in BC. Methods The expression level of hsa_circ_0005273 and miR-200a-3p were examined by RT-qPCR in BC tissues and cell lines. The effect of knocking down hsa_circ_0005273 in BC cell lines were evaluated by examinations of cell proliferation, migration and cell cycle. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. RNA immunoprecipitation assay, RNA probe pull-down assay, luciferase reporter assay and fluorescence in situ hybridization were conducted to confirm the relationship between hsa_circ_0005273, miR-200a-3p and YAP1. Results Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of hsa_circ_0005273 inhibited the progression of BC cells in vitro and in vivo, while overexpression of hsa_circ_0005273 exhibited the opposite effect. Importantly, hsa_circ_0005273 upregulated YAP1 expression and inactivated Hippo pathway via sponging miR-200a-3p to promote BC progression. Conclusions Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and inactivates Hippo signaling pathway to promote BC progression, which may become a potential biomarker and therapeutic target.

scholarly journals Phosphatidylserine-Gold Nanoparticles (PS-AuNP) Induce Prostate and Breast Cancer Cell Apoptosis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1094
Author(s):  
Allan Radaic ◽  
Nam E. Joo ◽  
Soo-Hwan Jeong ◽  
Seong-II Yoo ◽  
Nicholas Kotov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gold Nanoparticles ◽  
Biomedical Applications ◽  
Therapeutic Potential ◽  
Control Treatment ◽  
Track Record ◽  
Males And Females ◽  
Breast And Prostate Cancer ◽  
First Time

Prostate and breast cancer are the current leading causes of new cancer cases in males and females, respectively. Phosphatidylserine (PS) is an essential lipid that mediates macrophage efferocytosis and is dysregulated in tumors. Therefore, developing therapies that selectively restore PS may be a potential therapeutic approach for carcinogenesis. Among the nanomedicine strategies for delivering PS, biocompatible gold nanoparticles (AuNPs) have an extensive track record in biomedical applications. In this study, we synthesized biomimetic phosphatidylserine-caped gold nanoparticles (PS-AuNPs) and tested their anticancer potential in breast and prostate cancer cells in vitro. We found that both cell lines exhibited changes in cell morphology indicative of apoptosis. After evaluating for histone-associated DNA fragments, a hallmark of apoptosis, we found significant increases in DNA fragmentation upon PS-AuNP treatment compared to the control treatment. These findings demonstrate the use of phosphatidylserine coupled with gold nanoparticles as a potential treatment for prostate and breast cancer. To the best of our knowledge, this is the first time that a phosphatidylserine-capped AuNP has been examined for its therapeutic potential in cancer therapy.

scholarly journals Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Miao-Miao Zhao ◽  
Wei-Li Yang ◽  
Fang-Yuan Yang ◽  
Li Zhang ◽  
Wei-Jin Huang ◽  
...  
Keyword(s):  
Drug Development ◽  
Cathepsin L ◽  
Human Cells ◽  
New Drugs ◽  
Disease Course ◽  
Promising Target ◽  
First Time

AbstractTo discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.

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