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2.
Reprod Biomed Online ; 44(5): 777-790, 2022 05.
Article in English | MEDLINE | ID: mdl-35337736

ABSTRACT

RESEARCH QUESTION: What is the role of exosomal lncRNAs and mRNAs profiles and their interaction networks in regulating the development of polycystic ovary syndrome (PCOS)? DESIGN: LncRNA microarray was used to analyse the expression profiles of lncRNA and mRNA in follicular fluid exosomes from three patients with polycystic ovary syndrome (PCOS) and three control women. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied to explore biological functions of exosomal mRNAs in PCOS. Six PCOS-related genes were selected, and coding-non-coding gene co-expression (CNC) networks and competing endogenous RNA (ceRNA) networks analysis were combined to reveal lncRNA-miRNA-mRNA interaction networks. RESULTS: A total of 5373 differentially expressed exosomal lncRNAs and 3381 differentially expressed exosomal mRNAs were identified (fold change ≥2 and P < 0.05). Gene ontology analysis indicated that 14 terms of biological process were related to reproductive development. KEGG pathway analysis revealed PCOS-related pathways, such as MAPK signalling pathway and some inflammation-related signalling pathways. Interaction networks of lncRNAs, miRNAs and six PCOS-related genes (IRS1, CYP11A1, BMP6, FSHR, WNT4 and CYP19A1) were constructed. The CNC networks and ceRNA networks analysis uncovered some novel PCOS-related exosomal lncRNA-miRNA-mRNA regulatory networks. CONCLUSIONS: Differential expression profiles of exosomal lncRNAs and mRNAs were identified, and some PCOS-related biological processes and regulatory networks were indicated. LncRNAs and mRNAs in follicular fluid exosomes may play important roles in the follicular development of PCOS.


Subject(s)
MicroRNAs , Polycystic Ovary Syndrome , RNA, Long Noncoding , Computational Biology , Female , Gene Expression Profiling , Gene Regulatory Networks , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Polycystic Ovary Syndrome/genetics , RNA, Long Noncoding/genetics , RNA, Messenger/genetics
3.
Cell Death Dis ; 11(7): 522, 2020 07 10.
Article in English | MEDLINE | ID: mdl-32651355

ABSTRACT

Growing evidences illustrated that long non-coding RNAs (lncRNAs) exhibited widespread effects on the progression of human cancers via various mechanisms. Long intergenic non-protein-coding RNA 01446 (LINC01446), a 3484-bp ncRNA, is known to locate at chromosome 7p12.1. However, its biological functions and specific action mechanism in gastric cancer (GC) are still unclear. In our study, LINC01446 was proved to be markedly upregulated in GC tissues relative to the normal tissues, and positively correlated with the poor survival of GC patients. The multivariate Cox regression model showed that LINC01446 functioned as an independent prognostic factor for the survival of GC patients. Functionally, LINC01446 facilitated the proliferation and metastasis of GC cells. Moreover, RNA-seq analysis demonstrated that LINC01446 knockdown primarily regulated the genes relating to the growth and migration of GC. Mechanistically, LINC01446 could widely interact with histone lysine-specific demethylase LSD1 and recruit LSD1 to the Ras-related dexamethasone-induced 1 (RASD1) promoter, thereby suppressing RASD1 transcription. Overall, these findings suggest that LINC01446/LSD1/RASD1 regulatory axis may provide bona fide targets for anti-GC therapies.


Subject(s)
Histone Demethylases/metabolism , RNA, Long Noncoding/genetics , Stomach Neoplasms/metabolism , Cell Proliferation/physiology , Disease Progression , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology
4.
Reprod Biomed Online ; 41(2): 170-181, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32593507

ABSTRACT

RESEARCH QUESTION: What is the expression pattern of microRNA (miRNA) in exosomes isolated from eutopic endometrial stromal cells (EuESC) of women with endometriosis-associated infertility? DESIGN: Small RNA sequencing was conducted in exosomes isolated from EuESC of women with endometriosis-associated infertility (n = 3) and normal endometrial stromal cells (NESC) of fertile women without endometriosis (n = 3). The differentially expressed miRNA in exosomes derived from EuESC and NESC were identified. The functions of the differentially expressed miRNA were analysed by gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. RESULTS: Small RNA sequencing showed that the percentages of exosomal miRNA in the total small RNA isolated from EuESC and NESC were not significantly different (P = 0.7804). A total of 49 differentially expressed miRNA (fold change >1.5 and P < 0.05) were identified, including 26 up-regulated and 23 down-regulated in EuESC exosomes as compared with NESC exosomes. Functional analysis revealed that 12 miRNA were predicted to target homeobox A10 (HOXA10) and/or the leukaemia inhibitory factor (LIF) 3' untranslated region (UTR). Both HOXA10 and LIF mRNA expression levels were significantly decreased in EuESC compared with NESC (P = 0.0222 and 0.0395, respectively). In addition, the predicated target genes of these differentially expressed exosomal miRNA were significantly (P < 0.05) enriched in 76 pathways, including the MAPK and Wnt signalling pathways. CONCLUSIONS: The differential expression patterns of exosomal miRNA were identified. Many exosomal miRNA may be involved in regulating the endometrial receptivity of women with endometriosis-associated infertility.


Subject(s)
Endometriosis/metabolism , Endometrium/metabolism , Exosomes/metabolism , Gene Expression , Infertility, Female/metabolism , MicroRNAs/metabolism , Stromal Cells/metabolism , Adult , Endometriosis/complications , Endometriosis/genetics , Female , Humans , Infertility, Female/etiology , Infertility, Female/genetics , MicroRNAs/genetics , Young Adult
5.
Mol Ther Nucleic Acids ; 19: 1164-1175, 2020 Mar 06.
Article in English | MEDLINE | ID: mdl-32059342

ABSTRACT

Non-protein-coding functional elements in the human genome in the postgenomic biology field have been drawing great attention in recent years. Thousands of long non-coding RNAs (lncRNAs) have been found to be expressed in various tumors. Yet only a small proportion of these lncRNAs have been well characterized. We have demonstrated that LINC00460 could affect cell proliferation through epigenetic regulation of KLF2 and CUL4A in human colorectal cancer. However, the clinical significance and biological role of LINC00460 in gastric cancer (GC) remain largely unknown. In this research, we discovered that LINC00460 is remarkably upregulated in GC tissues compared to the non-tumor tissues. Additionally, LINC00460 served as an independent prognostic marker in GC. Functionally, proliferation of GC cells could be regulated by LINC00460 both in vitro and in vivo. RNA sequencing (RNA-seq) analysis for the whole transcriptome indicated that LINC00460 may serve as a key regulatory factor in the tumorigenesis of GC. What's more, the biological function of LINC00460 was mediated, to certain extent, by the direct interaction with enhancer of zeste homolog 2 (EZH2) and lysine (K)-specific demethylase 1A (LSD1) proteins. Further analyses indicated that LINC00460 promoted GC proliferation at least partly through the downregulation of tumor suppressor-gene Cyclin G2 (CCNG2), which is mediated by EZH2 and LSD1. In conclusion, our results suggested that LINC00460 acted as an oncogene in GC to inhibit the expression of CCNG2 at least partly by binding with EZH2 and LSD1. Our study could provide additional insights into the development of novel target therapeutic methods for GC.

6.
Cancer Commun (Lond) ; 38(1): 64, 2018 10 26.
Article in English | MEDLINE | ID: mdl-30367681

ABSTRACT

BACKGROUND: Recent studies highlight pseudogene derived long non-coding RNAs (lncRNAs) as key regulators of cancer biology. However, few of them have been well characterized in pancreatic cancer. Here, we aimed to identify the association between pseudogene derived lncRNA DUXAP8 and growth of pancreatic cancer cells. METHODS: We screened for pseudogene derived lncRNAs associated with human pancreatic cancer by comparative analysis of three independent datasets from GEO. Quantitative real-time reverse transcription polymerase chain reaction was used to assess the relative expression of DUXAP8 in pancreatic cancer tissues and cells. Loss-of-function approaches were used to investigate the potential functional roles of DUXAP8 in pancreatic cancer cell proliferation and apoptosis in vitro and in vivo. RNA immunoprecipitation, chromosome immunoprecipitation assay and rescue experiments were performed to analyze the association of DUXAP8 with target proteins and genes in pancreatic cancer cells. RESULTS: Pancreatic cancer tissues had significantly higher DUXAP8 levels than paired adjacent normal tissues. High DUXAP8 expression was associated with a larger tumor size, advanced pathological stage and shorter overall survival of pancreatic cancer patients. Moreover, silencing DUXAP8 expression by siRNA or shRNA inhibited pancreatic cancer cell proliferation and promoted apoptosis in vitro and in vivo. Mechanistic analyses indicated that DUXAP8 regulates PC cell proliferation partly through downregulation of tumor suppressor CDKN1A and KLF2 expression. CONCLUSION: Our results suggest that tumor expression of pseudogene derived lncRNA DUXAP8 plays an important role in pancreatic cancer progression. DUXAP8 may serve as a candidate biomarker and represent a novel therapeutic target of pancreatic cancer.


Subject(s)
Cyclin-Dependent Kinase Inhibitor p21/metabolism , Kruppel-Like Transcription Factors/metabolism , RNA, Long Noncoding/metabolism , Aged , Animals , Cell Line, Tumor , Cell Proliferation/genetics , Cyclin-Dependent Kinase Inhibitor p21/genetics , Down-Regulation , Epigenesis, Genetic , Female , Heterografts , Humans , Kruppel-Like Transcription Factors/genetics , Male , Mice , Mice, Nude , Pseudogenes , RNA, Long Noncoding/genetics , Transfection
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