scholarly journals Inhibition of miR-141 and miR-200a Increase DLC-1 and ZEB2 Expression, Enhance Migration and Invasion in Metastatic Serous Ovarian Cancer

2020 ◽  
Vol 17 (8) ◽  
pp. 2766 ◽  
Author(s):  
Norhazlina Abdul Wahab ◽  
Zahreena Othman ◽  
Noor Wahidah Mohd Nasri ◽  
Mohd Helmy Mokhtar ◽  
Siti Fatimah Ibrahim ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Differentially Expressed ◽  
Locked Nucleic Acid ◽  
Migration And Invasion ◽  
Serous Ovarian Cancer ◽  
Novel Mirna ◽  
Ovarian Carcinogenesis ◽  
Differentially Expressed Mirnas

The role of microRNA (miRNA) in ovarian cancer has been extensively studied as a regulator for its targeted genes. However, its specific role in metastatic serous ovarian cancer (SOC) is yet to be explored. This paper aims to investigate the differentially expressed miRNAs in metastatic SOC compared to normal. Locked nucleic acid PCR was performed to profile miRNA expression in 11 snap frozen metastatic SOC and 13 normal ovarian tissues. Functional analysis and regulation of their targeted genes were assessed in vitro. Forty-eight miRNAs were significantly differentially expressed in metastatic SOC as compared to normal. MiR-19a is a novel miRNA to be upregulated in metastatic SOC compared to normal. DLC1 is possibly regulated by miR-141 in SOC. MiR-141 inhibition led to significantly reduced cell viability. Cell migration and invasion were significantly increased following miRNA inhibition. This study showed the aberrantly expressed miRNAs in metastatic SOC and the roles of miRNAs in the regulation of their targeted genes and ovarian carcinogenesis.

scholarly journals KLF7: a new candidate biomarker and therapeutic target for high-grade serous ovarian cancer

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Marta De Donato ◽  
Gabriele Babini ◽  
Simona Mozzetti ◽  
Marianna Buttarelli ◽  
Alessandra Ciucci ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Prognostic Marker ◽  
Late Stage ◽  
Therapeutic Target ◽  
Family Members ◽  
High Grade ◽  
Serous Ovarian Cancer

Abstract Background In spite of great progress in the surgical and clinical management, until now no significant improvement in overall survival of High-Grade Serous Ovarian Cancer (HGSOC) patients has been achieved. Important aspects for disease control remain unresolved, including unclear pathogenesis, high heterogeneity and relapse resistance after chemotherapy. Therefore, further research on molecular mechanisms involved in cancer progression are needed to find new targets for disease management. The Krüppel-like factors (KLFs) are a family of transcriptional regulators controlling several basic cellular processes, including proliferation, differentiation and migration. They have been shown to play a role in various cancer-relevant processes, in a context-dependent way. Methods To investigate a possible role of KLF family members as prognostic biomarkers, we carried out a bioinformatic meta-analysis of ovarian transcriptome datasets in different cohorts of late-stage HGSOC patients. In vitro cellular models of HGSOC were used for functional studies exploring the role of KLF7 in disease development and progression. Finally, molecular modelling and virtual screening were performed to identify putative KLF7 inhibitors. Results Bioinformatic analysis highlighted KLF7 as the most significant prognostic gene, among the 17 family members. Univariate and multivariate analyses identified KLF7 as an unfavourable prognostic marker for overall survival in late-stage TCGA-OV and GSE26712 HGSOC cohorts. Functional in vitro studies demonstrated that KLF7 can play a role as oncogene, driving tumour growth and dissemination. Mechanistic targets of KLF7 included genes involved in epithelial to mesenchymal transition, and in maintaining pluripotency and self-renewal characteristics of cancer stem cells. Finally, in silico analysis provided reliable information for drug-target interaction prediction. Conclusions Results from the present study provide the first evidence for an oncogenic role of KLF7 in HGSOC, suggesting it as a promising prognostic marker and therapeutic target.

scholarly journals New Actors Driving the Epithelial–Mesenchymal Transition in Cancer: The Role of Leptin

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1676
Author(s):  
Monserrat Olea-Flores ◽  
Juan C. Juárez-Cruz ◽  
Miriam D. Zuñiga-Eulogio ◽  
Erika Acosta ◽  
Eduardo García-Rodríguez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Progression ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Epithelial Cancers ◽  
Patients With Cancer

Leptin is a hormone secreted mainly by adipocytes; physiologically, it participates in the control of appetite and energy expenditure. However, it has also been linked to tumor progression in different epithelial cancers. In this review, we describe the effect of leptin on epithelial–mesenchymal transition (EMT) markers in different study models, including in vitro, in vivo, and patient studies and in various types of cancer, including breast, prostate, lung, and ovarian cancer. The different studies report that leptin promotes the expression of mesenchymal markers and a decrease in epithelial markers, in addition to promoting EMT-related processes such as cell migration and invasion and poor prognosis in patients with cancer. Finally, we report that leptin has the greatest biological relevance in EMT and tumor progression in breast, lung, prostate, esophageal, and ovarian cancer. This relationship could be due to the key role played by the enriched tumor microenvironment in adipose tissue. Together, these findings demonstrate that leptin is a key biomolecule that drives EMT and metastasis in cancer.

scholarly journals Age-Related Changes in MicroRNA in the Rat Pituitary and Potential Role in GH Regulation

2018 ◽  
Vol 19 (7) ◽  
pp. 2058 ◽  
Author(s):  
Haojie Zhang ◽  
Qien Qi ◽  
Ting Chen ◽  
Junyi Luo ◽  
Qianyun Xi ◽  
...  
Keyword(s):  
Growth Process ◽  
Potential Role ◽  
Differentially Expressed ◽  
Mirna Microarray ◽  
Pituitary Development ◽  
Age Related ◽  
Rat Pituitary ◽  
Differentially Expressed Mirnas

The growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis has recently been recognized as an important factor related to the longevity of many organisms. MicroRNAs (miRNAs or miRs) could also participate in diverse biological processes. However, the role of miRNAs in the decline of pituitary GH during the growth process remains unclear. To better characterize the effects of miRNAs on the pituitary, we used a miRNA microarray to investigate the miRNA profile in the rat pituitary from postnatal development throughout the growth process. Then, in vitro experiments were conducted to analyze the miRNAs’ potential roles related to GH regulation. Taken together, the microarray results indicated that there were 22 miRNAs differentially expressed during pituitary development. The bioinformatics analysis suggested that the most differentially expressed miRNAs may participate in multiple pathways associated with the pituitary function. Furthermore, the in vitro findings demonstrated that miR-141-3p was involved in GH regulation.

scholarly journals Identification of Key lncRNA–mRNA Pairs and Functional lncRNAs in Breast Cancer by Integrative Analysis of TCGA Data

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhe Li ◽  
Zheng Qian ◽  
Fei Chen ◽  
Shujun Jiang ◽  
Lingjia Meng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcriptional Regulatory Network ◽  
Differentially Expressed ◽  
Cancer Drug ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Differentially Expressed Mirnas ◽  
Key Genes ◽  
Cox Analysis

Long non-coding RNAs (lncRNAs) play an important role in many diseases and are involved in the post-transcriptional regulatory network of tumors. The purpose of this study is to mine new lncRNA–mRNA regulatory pairs and analyze the new mechanism of lncRNA involvement in breast cancer progression. Using breast cancer miRNA and mRNA expression profiling from The Cancer Genome Atlas (TCGA), we identified 59 differentially expressed lncRNAs, 88 differentially expressed miRNAs, and 1,465 differentially expressed mRNAs between breast cancer tissue and adjacent normal breast cancer. Whereafter, four candidate lncRNAs (FGF14-AS2, LINC01235, AC055854.1, and AC124798.1) were identified by the Kaplan–Meier (K–M) plotter. Furthermore, we screened the hub lncRNA (LINC01235) through univariate Cox analysis, multivariate Cox analysis, and qPCR validation, which was significantly correlated with breast cancer stage, ER status, and pathological N. Subsequently, 107 LINC01235-related mRNAs were obtained by combining differentially expressed miRNAs, differentially expressed mRNAs, and LINC01235 targeting miRNAs and mRNAs. The protein–protein interaction (PPI) network was established by Cytoscape software, and 53 key genes were screened. Function and pathway enrichment showed that LINC01235-related key genes might be involved in the process of cell differentiation, cell proliferation, and p53 signal pathway. In addition, LINC01235 has been confirmed to regulate the proliferation, migration, and invasion of MCF-7 cells in in vitro experiments. Furthermore, we screened three mRNAs (ESR1, ADRA2A, and DTL) associated with breast cancer drug resistance from key genes. Through RNA interference experiments in vitro and correlation analysis, we found that there was a negative feedback mechanism between LINC01235 and ESR1/ADRA2A. In conclusion, our results suggest that LINC01235-ESR1 and LINC01235-ADRA2A could serve as important co-expression pairs in the progression of breast cancer, and LINC01235 plays a key role as an independent prognostic factor in patients with breast cancer. The findings of this work greatly increase our understanding of the molecular regulatory mechanisms of lncRNA in breast cancer.

scholarly journals Down-regulation of PADI2 prevents proliferation and epithelial-mesenchymal transition in ovarian cancer through inhibiting JAK2/STAT3 pathway in vitro and in vivo, alone or in combination with Olaparib

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Lidong Liu ◽  
Zhiwei Zhang ◽  
Guoxiang Zhang ◽  
Ting Wang ◽  
Yingchun Ma ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Combination Treatment ◽  
Migration And Invasion ◽  
Link Type ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Skov3 Cells

Abstract Background Epithelial ovarian cancer (EOC) is the most lethal disease among female genital malignant tumors. Peptidylarginine deiminase type II(PADI II) has been shown to enhance a variety of cancers carcinogenesis, including ovarian cancer. The purpose of this study was to investigate the biological role of PADI2 in ovarian cancer (OC) and the relative mechanism. Methods Gene Expression Profiling Interactive Analysis (GEPIA) (https://gepia.pku.cn/) and ONCOMINE (https://www.oncomine.org/) were used to analyze PADI2 Gene Expression data. The survival curve for the PADI2 gene was generated by using the online Kaplan–Meier mapping site (https://www.kmplot.com/). We conducted MTT assay, cloning formation assay and EdU cell proliferation assay to detect the cell activity of PADI2 knockdown A2780 and SKOV3 ovarian cancer cells treated with Olaparib. Cell migration and invasion were observed by would healing and transwell assay. The pathway changes after the treatment of PADI2 were detected by transcriptome sequencing and western blot. The role of PADI2 combined with Olaparib treatment in vivo was studied in nude mouse model bearing ovarian cancer tumor. Results We investigated the role of PADI2 on EOC in vitro and in vivo. PADI2 was upregulated in ovarian cancer samples and high PADI2 expression was correlated with poor outcome. Downregulating PADI2 suppressed colony formation, proliferation, migration and invasion of A2780 and SKOV3 cells. Furthermore, downregulating PADI2 and Olaparib combination treatment attenuated the viability, migration and invasion of A2780 and SKOV3 cells. We identified differentially expressed genes in A2780-shPADI2 and SKOV3-shPADI2 cell by transcriptome sequencing analysis and verified that downregulating PADI2 and Olaparib combination treatment suppresses EMT and JAK2/STAT3 signaling pathway in A2780 and SKOV3 cells in vitro and in vivo. Conclusions Downregulation of PADI2 and Olaparib combination treatment attenuated the proliferation, migration and invasion of A2780 and SKOV3 cells by inhibiting the EMT through JAK2/STAT3 signaling pathway.

scholarly journals CYPA promotes the progression and metastasis of serous ovarian cancer (SOC) in vitro and in vivo

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhi-Ying Qi ◽  
Fang Wang ◽  
Ying-Ying Yue ◽  
Xue-Wang Guo ◽  
Rui-Meng Guo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Immune Modulation ◽  
Clinical Stage ◽  
Migration And Invasion ◽  
Serous Ovarian Cancer ◽  
Promising Therapeutic Target ◽  
Lymphnode Metastasis

AbstractOvarian cancer (OC) is a type of gynaecological malignancy with high mortality in females. Serous ovarian cancer (SOC) is a distinct subtype of OC with poor early diagnosis. Given the limitations of traditional therapies, such as chemotherapy, targeted treatment is therefore a promising therapy to improve the survival rate of SOC patients. Cyclophilin A (CYPA) is a member of Cyclophilin family and thought to participates in multiple cellular processes such as cell transduction and immune modulation. Recently, various of studies indicated that CYPA has critical impact on cancer progression. CYPA could regulate cell proliferation, invasion, and chemoresistance of multiple types of cancers. However, it is still unclear whether it could affect ovarian cancer. In this study, we demonstrated that CYPA was highly expressed in SOC tissues compared with adjacent tissues. Further, CYPA was significantly associated with clinical stage and lymphnode metastasis of SOC patients. Additionally, data indicated that knockdown of CYPA by its shRNA dramatically reduces migration and invasion capacity of SOC cells in vitro and blocks tumor metastasis in vivo. Our study investigates the involvement of CYPA in the progression and metastasis of SOC, and therefore provides CYPA as a promising therapeutic target for SOC treatment.

scholarly journals Interaction of E3 Ubiquitin Ligase MARCH7 with Long Noncoding RNA MALAT1 and Autophagy-Related Protein ATG7 Promotes Autophagy and Invasion in Ovarian Cancer

2018 ◽  
Vol 47 (2) ◽  
pp. 654-666 ◽  
Author(s):  
Jianguo Hu ◽  
Luo Zhang ◽  
Zhiqiang Mei ◽  
Yuan Jiang ◽  
Yuan Yi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Xenograft Model ◽  
E3 Ligase ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Ubiquitin E3 Ligase ◽  
Skov3 Cells

Background/Aims: Ubiquitin E3 ligase MARCH7 plays an important role in T cell proliferation and neuronal development. But its role in ovarian cancer remains unclear. This study aimed to investigate the role of Ubiquitin E3 ligase MARCH7 in ovarian cancer. Methods: Real-time PCR, immunohistochemistry and western blotting analysis were performed to determine the expression of MARCH7, MALAT1 and ATG7 in ovarian cancer cell lines and clinical specimens. The role of MARCH7 in maintaining ovarian cancer malignant phenotype was examined by Wound healing assay, Matrigel invasion assays and Mouse orthotopic xenograft model. Luciferase reporter assay, western blot analysis and ChIP assay were used to determine whether MARCH7 activates TGF-β-smad2/3 pathway by interacting with TGFβR2. Results: MARCH7 interacted with MALAT1 by miR-200a (microRNA-200a). MARCH7 may function as a competing endogenous RNA (ceRNA) to regulate the expression of ATG7 by competing with miR-200a. MARCH7 regulated TGF-β-smad2/3 pathway by interacting with TGFβR2. Inhibition of TGF-β-smad2/3 pathway downregulated MARCH7, MALAT1 and ATG7. MiR-200a regulated TGF-β induced autophagy, invasion and metastasis of SKOV3 cells by targeting MARCH7. MARCH7 silencing inhibited autophagy invasion and metastasis of SKOV3 cells both in vitro and in vivo. In contrast, MARCH7 overexpression promoted TGF-β induced autophagy, invasion and metastasis of A2780 cells in vitro by depending on MALAT1 and ATG7. We also found that TGF-β-smad2/3 pathway regulated MARCH7 and ATG7 through MALAT1. Conclusions: These findings suggested that TGFβR2-Smad2/3-MALAT1/MARCH7/ATG7 feedback loop mediated autophagy, migration and invasion in ovarian cancer.

scholarly journals HOXB4 promotes the malignant progression of ovarian cancer via DHDDS

2020 ◽  
Author(s):  
Na Li ◽  
Jin-hai Gou ◽  
Jiao Xiong ◽  
Juan-juan You ◽  
Zhengyu Li
Keyword(s):  
Ovarian Cancer ◽  
Poor Prognosis ◽  
Tumor Model ◽  
Malignant Progression ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Proliferation And Invasion

Abstract Background : Homeobox B4 (HOXB4) is correlated with poor prognosis of various cancer types. However, how HOXB4 promotes ovarian cancer (OV) progression remains unclear. Methods : The Cancer Genome Atlas (TCGA) database indicated that a high level of HOXB4 in OV was correlated with poor prognosis. The biological functions of HOXB4 were confirmed by colony formation, migration, and invasion assays. The effect of HOXB4 on the expression of EMT cell markers was determined. The transcriptional target of HOXB4 was DHDDS, which was detected by a ChIP assay. A xenograft tumor model was generated in nude mice to detect the role of HOXB4 in tumor proliferation and metastasis. Results : The results showed that HOXB4 protein levels were higher in OV tissues than in normal tissues and correlated with poor prognosis of OV. HOXB4 reduction inhibited the proliferation and invasion ability of OV cells in vitro. Conversely, these effects were enhanced by the upregulation of HOXB4 in OV cells. The binding of HOXB4 to two DNA motifs regulated DHDDS expression and contributed to the malignant progression of OV. The role of HOXB4 in contributing to tumor development in vivo was verified in mice. Further results indicated that HOXB4 induced Snail and Zeb1 expression. Conclusion : Overall, HOXB4 overexpression was remarkably correlated with poor prognosis of OV. Mechanistically, HOXB4 enhances the proliferation and invasion of tumor cells by activating DHDDS, thereby promoting the malignant progression of OV.

scholarly journals HOXB4 promotes the malignant progression of ovarian cancer via DHDDS

2020 ◽  
Author(s):  
Na Li ◽  
Jiao Xiong ◽  
Zhengyu Li
Keyword(s):  
Ovarian Cancer ◽  
Poor Prognosis ◽  
Tumor Model ◽  
Malignant Progression ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Proliferation And Invasion

Abstract Background : Homeobox B4 (HOXB4) is correlated with poor prognosis of various cancer types. However, how HOXB4 promotes ovarian cancer (OV) progression remains unclear. Methods : The Cancer Genome Atlas (TCGA) database indicated that a high level of HOXB4 in OV was correlated with poor prognosis. The biological functions of HOXB4 were confirmed by colony formation, migration, and invasion assays. The effect of HOXB4 on the expression of EMT cell markers was determined. The transcriptional target of HOXB4 was DHDDS, which was detected by a ChIP assay. A xenograft tumor model was generated in nude mice to detect the role of HOXB4 in tumor proliferation and metastasis. Results : The results showed that HOXB4 protein levels were higher in OV tissues than in normal tissues and correlated with poor prognosis of OV. HOXB4 reduction inhibited the proliferation and invasion ability of OV cells in vitro. Conversely, these effects were enhanced by the upregulation of HOXB4 in OV cells. The binding of HOXB4 to two DNA motifs regulated DHDDS expression and contributed to the malignant progression of OV. The role of HOXB4 in contributing to tumor development in vivo was verified in mice. Further results indicated that HOXB4 induced Snail and Zeb1 expression. Conclusion : Overall, HOXB4 overexpression was remarkably correlated with poor prognosis of OV. Mechanistically, HOXB4 enhances the proliferation and invasion of tumor cells by activating DHDDS, thereby promoting the malignant progression of OV.

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