Characteristic Analysis from Excessive to Deficient Syndromes in Hepatocarcinoma Underlying miRNA Array Data

Traditional Chinese medicine (TCM) treatment is regarded as a safe and effective method for many diseases. In this study, the characteristics among excessive, excessive-deficient, and deficient syndromes of Hepatocellular carcinoma (HCC) were studied using miRNA array data. We first calculated the differentially expressed miRNAs based on random modulet-test and classified three TCM syndromes of HCC using SVM method. Then, the weighted miRNA-target networks were constructed for different TCM syndromes using predicted miRNA targets. Subsequently, the prioritized target genes of upexpression network of TCM syndromes were analyzed using DAVID online analysis. The results showed that there are distinctly different hierarchical cluster and network structure of TCM syndromes in HCC, but the excessive-deficient combination syndrome is extrinsically close to deficient syndrome. GO and pathway analysis revealed that the molecular mechanisms of excessive-deficient and deficient syndromes of HCC are more complex than excessive syndrome. Furthermore, although excessive-deficient and deficient syndromes have similar complex mechanisms, excessive-deficient syndrome is more involved than deficient syndrome in development of cancer process. This study suggested that miRNAs might be important mediators involved in the changing process from excessive to deficient syndromes and could be potential molecular markers for the diagnosis of TCM syndromes in HCC.

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Progression from Excessive to Deficient Syndromes in Chronic Hepatitis B: A Dynamical Network Analysis of miRNA Array Data

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/945245 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 6

Author(s):

Qi-Long Chen ◽

Yi-Yu Lu ◽

Gui-Biao Zhang ◽

Ya-Nan Song ◽

Qian-Mei Zhou ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Mirna Target ◽

Molecular Mechanisms ◽

Target Genes ◽

Hierarchical Cluster ◽

Mirna Array ◽

Target Network ◽

The Difference

Traditional Chinese medicine (TCM) treatment is regarded as a safe and effective method for chronic hepatitis B (CHB), which requires a traditional diagnosis method to distinguish the TCM syndrome. In this study, we study the differences and similarities among excessive, excessive-deficient, and deficient syndromes, by an integrative and comparative analysis of weighted miRNA expression or miRNA-target network in CHB patients. We first calculated the differential expressed miRNAs based on random modulet-test and classified three CHB TCM syndromes using SVM method. Then, miRNA target genes were obtained by validated database and predicted programs subsequently, the weighted miRNA-target networks were constructed for different TCM syndromes. Furthermore, prioritize target genes of networks of CHB TCM syndromes progression analyzed using DAVID online analysis. The results have shown that the difference between TCM syndromes is distinctly based on hierarchical cluster and network structure. GO and pathway analysis implicated that three CHB syndromes more likely have different molecular mechanisms, while the excessive-deficient and deficient syndromes are more dangerous than excessive syndrome in the process of tumorigenesis. This study suggested that miRNAs are important mediators for TCM syndromes classification as well as CHB development progression and therefore could be potential diagnosis and therapeutic molecular markers.

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Identification and validation of key miRNAs and miRNA–mRNA regulatory network associated with uterine involution in postpartum Kazakh sheep

Archives Animal Breeding ◽

10.5194/aab-64-119-2021 ◽

2021 ◽

Vol 64 (1) ◽

pp. 119-129

Author(s):

Heng Yang ◽

Lin Fu ◽

Qifeng Luo ◽

Licai Li ◽

Fangling Zheng ◽

...

Keyword(s):

Mirna Target ◽

Molecular Mechanisms ◽

Target Genes ◽

Gene Prediction ◽

Biological Effects ◽

Differentially Expressed ◽

Illumina Hiseq ◽

Go Annotation ◽

Uterine Involution ◽

Differentially Expressed Mirnas

Abstract. MicroRNAs (miRNAs) are widely expressed in different mammalian tissues and exert their biological effects through corresponding target genes. miRNA target genes can be rapidly and efficiently identified and screened by combining bioinformatics prediction and experimental validation. To investigate the possible molecular regulatory mechanisms involving miRNAs during uterine involution in postpartum ewes, we used Illumina HiSeq sequencing technology to screen for the number and characteristics of miRNAs in faster uterine involution and normal uterine involution group. A total of 118 differentially expressed miRNAs, including 33 known miRNAs and 85 new miRNAs, were identified in the hypothalamic library, whereas 54 miRNAs, including 5 known miRNAs and 49 new miRNAs, were identified in the uterine library. Screening with four types of gene prediction software revealed 73 target genes associated with uterine involution, and subsequently, GO annotation and KEGG pathway analysis were performed. The results showed that, in the hypothalamic–uterine axis, uterine involution in postpartum ewes might primarily involve two miRNA-target gene pairs, namely, miRNA-200a–PTEN and miRNA-133–FGFR1, which can participate in GnRH signal transduction in the upstream hypothalamus and in the remodeling process at the downstream uterus, through the PI3K–AKT signaling pathway to influence the recovery of the morphology and functions of the uterus during the postpartum period in sheep. Therefore, identification of differentially expressed miRNAs in this study fills a gap in the research related to miRNAs in uterine involution in postpartum ewes and provides an important reference point for a comprehensive understanding of the molecular mechanisms underlying the regulation of postpartum uterine involution in female livestock.

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Comprehensive microRNA analysis in bleomycin-induced pulmonary fibrosis identifies multiple sites of molecular regulation

Physiological Genomics ◽

10.1152/physiolgenomics.00222.2010 ◽

2011 ◽

Vol 43 (9) ◽

pp. 479-487 ◽

Cited By ~ 73

Author(s):

Ting Xie ◽

Jiurong Liang ◽

Rishu Guo ◽

Ningshan Liu ◽

Paul W. Noble ◽

...

Keyword(s):

Lung Fibrosis ◽

Molecular Mechanisms ◽

Target Genes ◽

Expression Patterns ◽

Differentially Expressed ◽

Toll Like Receptor ◽

Mirna Array ◽

Differentially Expressed Mirnas ◽

Mouse Lungs ◽

Insight Into

The molecular mechanisms of lung injury and fibrosis are incompletely understood. MicroRNAs (miRNAs) are crucial biological regulators that act by suppressing their target genes and are involved in a variety of pathophysiological processes. To gain insight into miRNAs in the regulation of lung fibrosis, total RNA was isolated from mouse lungs harvested at different days after bleomycin treatment, and miRNA array with 1,810 miRNA probes was performed thereafter. MiRNAs expressed in lungs with bleomycin treatment at different time points were compared with miRNAs expressed in lungs without bleomycin treatment, resulting in 161 miRNAs differentially expressed. Furthermore, miRNA expression patterns regulated in initial and late periods after bleomycin were identified. Target genes were predicted in silico for differentially expressed miRNAs, including let-7f, let-7g, miR-196b, miR-16, miR-195, miR-25, miR-144, miR-351, miR-153, miR-468, miR-449b, miR-361, miR-700, miR-704, miR-717, miR-10a, miR-211, miR-34a, miR-367, and miR-21. Target genes were then cross-referenced to the molecular pathways, suggesting that the differentially expressed miRNAs regulate apoptosis, Wnt, Toll-like receptor, and TGF-β signaling. Our study demonstrated a relative abundance of miRNA levels in bleomycin-induced lung fibrosis. The miRNAs and their potential target genes identified may contribute to the understanding of the complex transcriptional program of lung fibrosis.

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Molecular Mechanisms Underlying Hepatocellular Carcinoma Induction by Aberrant NRF2 Activation-Mediated Transcription Networks: Interaction of NRF2-KEAP1 Controls the Fate of Hepatocarcinogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms21155378 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5378 ◽

Cited By ~ 2

Author(s):

Effi Haque ◽

M. Rezaul Karim ◽

Aamir Salam Teeli ◽

Magdalena Śmiech ◽

Paweł Leszczynski ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Leucine Zipper ◽

Molecular Mechanisms ◽

Target Genes ◽

Precancerous Lesions ◽

Redox Homeostasis ◽

Detoxification Enzymes ◽

Related Factor ◽

Basic Leucine Zipper ◽

Nrf2 Activation

NF-E2-related factor 2 (NRF2) is a basic leucine zipper transcription factor, a master regulator of redox homeostasis regulating a variety of genes for antioxidant and detoxification enzymes. NRF2 was, therefore, initially thought to protect the liver from oxidative stress. Recent studies, however, have revealed that mutations in NRF2 cause aberrant accumulation of NRF2 in the nucleus and exert the upregulation of NRF2 target genes. Moreover, among all molecular changes in hepatocellular carcinoma (HCC), NRF2 activation has been revealed as a more prominent pathway contributing to the progression of precancerous lesions to malignancy. Nevertheless, how its activation leads to poor prognosis in HCC patients remains unclear. In this review, we provide an overview of how aberrant activation of NRF2 triggers HCC development. We also summarize the emerging roles of other NRF family members in liver cancer development.

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Exosomal miR-1290 promotes angiogenesis in hepatocellular carcinoma via targeting SMEK1

10.21203/rs.2.13182/v2 ◽

2020 ◽

Author(s):

Qiong Wang ◽

Guanwen Wang ◽

Lianjie Niu ◽

Shaorong Zhao ◽

Jianjun Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Endothelial Cells ◽

Tumor Angiogenesis ◽

Molecular Mechanisms ◽

Target Genes ◽

Primary Liver Cancer ◽

Tumor Model ◽

Tube Formation ◽

Luciferase Reporter

Abstract Background: Hepatocellular carcinoma (HCC), the most common primary liver cancer, rely on the formation of new blood vessel for growth and frequent intrahepatic and extrahepatic metastasis. Therefore, it is important to explore the underlying molecular mechanisms of tumor angiogenesis of HCC. Recently, microRNAs have been shown to modulate angiogenic processes by modulating the expression of critical angiogenic factors. However, the potential roles of tumor-derived exosomal microRNAs in regulating tumor angiogenesis remain to be elucidated. Methods: MiRNome sequencing was performed to uncover the miRNAs that are dysregulated in HCC patient serum-derived exosomes. Expression levels of miR-1290 in tissues and cells were determined by quantitative real-time PCR. The effect of mir-1290 on proliferation was evaluated by CCK-8 assay. The angiogenic ability of cells were determined by transwell, wound-healing, tube formation and matrigel plug assays. SMMC-7721 xenograft tumor model was established in NOD-SCID nude mice using miR-1290 and NC antagomirs to determin the angiogenic effect of mir-1290 in vivo. Target protein expression was determined by western blotting. Dual luciferase reporter assay was performed to confirm the action of miR-1290 on downstream target genes including SMEK1. Results are reported as means ± S.D. and differences were tested for significance using 2-sided Student’s t-test.Results: In this study, our miRNome sequencing demonstrated that miR-1290 was overexpressed in HCC patient serum-derived exosomes, and we found that delivery of miR-1290 into human endothelial cells enhanced their angiogenic ability. Our results further revealed that SMEK1 is a direct target of miR-1290 in endothelial cells. MiR-1290 exerted its pro-angiogenic function, at least in part, by alleviating the inhibition of VEGFR2 phosphorylation done by SMEK1. Conclusions: Collectively, our findings provide evidence that miR-1290 is overexpressed in HCC and promotes tumor angiogenesis via exosomal secretion, implicating its potential role as a therapeutic target for HCC.

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Integrated analysis of sex-biased mRNA and miRNA expression profiles in the gonad of the discus fish (Symphysodon aequifasciatus)

10.1101/492264 ◽

2018 ◽

Cited By ~ 1

Author(s):

yuanshuai Fu ◽

Zhe Xu ◽

Zaizhong Chen ◽

Bin Wen ◽

Jianzhong Gao

Keyword(s):

Molecular Mechanisms ◽

Target Genes ◽

High Efficiency ◽

Expression Profiles ◽

Gonad Development ◽

Differentially Expressed ◽

Cdna Libraries ◽

Integrated Analysis ◽

Illumina Hiseq ◽

Differentially Expressed Mirnas

The discus fish (Symphysodon aequifasciatus) is an ornamental fish that is well-known around the world. Phenotype investigation indicated that there are no significant differences in appearance between males and females of the discus fish. To better understand the sexual development mechanisms and obtain a high efficiency sex identification method in the artificial reproduction process of the discus fish, we constructed six cDNA libraries from three adult testes and three adult ovaries, and perform RNA-sequencing for identifying sex-biased candidate genes, microRNA (miRNA), and metabolic pathway using the Illumina Hiseq 4000. A total of 50,082 non-redundant genes (unigenes) were identified, of which 18,570 unigenes were significantly overexpressed in testes, and 11,182 unigenes were significantly overexpressed in ovaries, and 8 differentially expressed unigenes were validated by quantitative Real-Time PCR (qPCR). A total of 551 miRNAs were identified, of which 47 miRNAs were differentially expressed between testes and ovaries, and 7 differentially expressed miRNAs and one non-differential miRNA were validated by qPCR. Twenty-four of these differentially expressed miRNAs and their 15 predicted target genes constituted 41 important miRNA-mRNA interaction pairs, which may be important candidates for sex-related miRNAs and sex-related genes in the discus fish. Some of vital sex-related metabolic pathways were also identified that may play key roles in regulating gonad development of the discus fish. These results can provide important insights to better understand molecular mechanisms for sexual dimorphism in gonads development.

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Genome-wide investigation of microRNAs and expression profiles during rhizome development in ginger (Zingiber officinale Roscoe)

BMC Genomics ◽

10.1186/s12864-021-08273-y ◽

2022 ◽

Vol 23 (1) ◽

Author(s):

Haitao Xing ◽

Yuan Li ◽

Yun Ren ◽

Ying Zhao ◽

Xiaoli Wu ◽

...

Keyword(s):

Mirna Target ◽

Molecular Mechanisms ◽

Target Genes ◽

Expression Profiles ◽

Expression Patterns ◽

Qrt Pcr ◽

Putative Target ◽

Genome Wide ◽

Ginger Rhizome ◽

Rhizome Development

Abstract Background MicroRNAs (miRNAs) are endogenous, non-coding small functional RNAs that govern the post-transcriptional regulatory system of gene expression and control the growth and development of plants. Ginger is an herb that is well-known for its flavor and medicinal properties. The genes involved in ginger rhizome development and secondary metabolism have been discovered, but the genome-wide identification of miRNAs and their overall expression profiles and targets during ginger rhizome development are largely unknown. In this study, we used BGISEQ-500 technology to perform genome-wide identification of miRNAs from the leaf, stem, root, flower, and rhizome of ginger during three development stages. Results In total, 104 novel miRNAs and 160 conserved miRNAs in 28 miRNA families were identified. A total of 181 putative target genes for novel miRNAs and 2772 putative target genes for conserved miRNAs were predicted. Transcriptional factors were the most abundant target genes of miRNAs, and 17, 9, 8, 4, 13, 8, 3 conserved miRNAs and 5, 7, 4, 5, 5, 15, 9 novel miRNAs showed significant tissue-specific expression patterns in leaf, stem, root, flower, and rhizome. Additionally, 53 miRNAs were regarded as rhizome development-associated miRNAs, which mostly participate in metabolism, signal transduction, transport, and catabolism, suggesting that these miRNAs and their target genes play important roles in the rhizome development of ginger. Twelve candidate miRNA target genes were selected, and then, their credibility was confirmed using qRT-PCR. As the result of qRT-PCR analysis, the expression of 12 candidate target genes showed an opposite pattern after comparison with their miRNAs. The rhizome development system of ginger was observed to be governed by miR156, miR319, miR171a_2, miR164, and miR529, which modulated the expression of the SPL, MYB, GRF, SCL, and NAC genes, respectively. Conclusion This is a deep genome-wide investigation of miRNA and identification of miRNAs involved in rhizome development in ginger. We identified 52 rhizome-related miRNAs and 392 target genes, and this provides an important basis for understanding the molecular mechanisms of the miRNA target genes that mediate rhizome development in ginger.

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Exosomal miR-1290 promotes angiogenesis in hepatocellular carcinoma via targeting SMEK1

10.21203/rs.2.13182/v1 ◽

2019 ◽

Author(s):

Qiong Wang ◽

Guanwen Wang ◽

Lianjie Niu ◽

Shaorong Zhao ◽

Jianjun Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Endothelial Cells ◽

Tumor Angiogenesis ◽

Molecular Mechanisms ◽

Target Genes ◽

Primary Liver Cancer ◽

Tumor Model ◽

Luciferase Reporter ◽

Dependent Manner

Abstract Abstract Background: Hepatocellular carcinoma (HCC), the most common primary liver cancer, rely on the formation of new blood vessel for growth and frequent intrahepatic and extrahepatic metastasis. Therefore, it is important to explore the underlying molecular mechanisms of tumor angiogenesis of HCC. Recently, microRNAs have been shown to modulate angiogenic processes by modulating the expression of critical angiogenic factors. However, the potential roles of tumor-derived exosomal microRNAs in regulating tumor angiogenesis remain to be elucidated. Methods: MiRNome sequencing was performed to uncover the miRNAs that are dysregulated in HCC patient serum-derived exosomes. Expression levels of miR-1290 in tissues and cells were determined by quantitative real-time PCR. The effect of mir-1290 on proliferation was evaluated by CCK-8 assay. The angiogenic ability of cells were determined by transwell, wound-healing, tube formation and matrigel plug assays. SMMC-7721 xenograft tumor model was established in NOD-SCID nude mice using miR-1290 and NC antagomirs to determin the angiogenic effect of mir-1290 in vivo. Target protein expression was determined by western blotting. Dual luciferase reporter assay was performed to confirm the action of miR-1290 on downstream target genes including SMEK1. Results are reported as means ± S.D. and differences were tested for significance using 2-sided Student’s t-test. Results: In this study, our miRNome sequencing demonstrated that miR-1290 was overexpressed in HCC patient serum-derived exosomes, and we found that delivery of miR-1290 into human endothelial cells enhanced their angiogenic ability. Our results further revealed that SMEK1 is a direct target of miR-1290 in endothelial cells. MiR-1290 exerted its pro-angiogenic function, at least in part, by inhibiting the VEGFR2 signaling pathway in a SMEK1-dependent manner. Conclusions: Collectively, our findings provide evidence that miR-1290 is overexpressed in HCC and promotes tumor angiogenesis via exosomal secretion, implicating its potential role as a therapeutic target for HCC.

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Joint RNA-Seq and miRNA Profiling Analyses to Reveal Molecular Mechanisms in Regulating Thickness of Pod Canopy in Brassica napus

Genes ◽

10.3390/genes10080591 ◽

2019 ◽

Vol 10 (8) ◽

pp. 591 ◽

Cited By ~ 1

Author(s):

Chen ◽

Huo ◽

Yang ◽

Jian ◽

Qu ◽

...

Keyword(s):

Brassica Napus ◽

Molecular Mechanisms ◽

Target Genes ◽

Differentially Expressed ◽

Oilseed Crop ◽

Flower Bud ◽

Mirna Profiling ◽

Differentially Expressed Mirnas ◽

Yield Formation ◽

Architecture Component

Oilseed rape (Brassica napus) is the second largest oilseed crop worldwide. As an architecture component of B. napus, thickness of pod canopy (TPC) plays an important role in yield formation, especially under high-density cultivation conditions. However, the mechanisms underlying the regulation of TPC remain unclear. RNA and microRNA (miRNA) profiling of two groups of B. napus lines with significantly different TPC at the bolting with a tiny bud stage revealed differential expressions of numerous genes involved in nitrogen-related pathways. Expression of several nitrogen-related response genes, including ASP5, ASP2, ASN3, ATCYSC1, PAL2, APT2, CRTISO, and COX15, was dramatically changed in the thick TPC lines compared to those in the thin TPC lines. Differentially expressed miRNAs also included many involved in nitrogen-related pathways. Expression of most target genes was negatively associated with corresponding miRNAs, such as miR159, miR6029, and miR827. In addition, 12 (including miR319, miR845, and miR158) differentially expressed miRNAs between two plant tissues sampled (stem apex and flower bud) were identified, implying that they might have roles in determining overall plant architecture. These results suggest that nitrogen signaling may play a pivotal role in regulating TPC in B. napus.

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A systemic study of indoxacarb resistance in Spodoptera litura revealed complex expression profiles and regulatory mechanism

Scientific Reports ◽

10.1038/s41598-019-51234-5 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 5

Author(s):

Li Shi ◽

Yao Shi ◽

Ya Zhang ◽

Xiaolan Liao

Keyword(s):

Spodoptera Litura ◽

Molecular Mechanisms ◽

Target Genes ◽

Expression Profiles ◽

Resistance Mechanisms ◽

Differentially Expressed ◽

Glutathione S Transferase ◽

Differentially Expressed Mirnas ◽

Important Pest ◽

Resistant Strains

Abstract The tobacco cutworm, Spodoptera litura, is an important pest of crop and vegetable plants worldwide, and its resistance to insecticides have quickly developed. However, the resistance mechanisms of this pest are still unclear. In this study, the change in mRNA and miRNA profiles in the susceptible, indoxacarb-resistant and field indoxacarb-resistant strains of S. litura were characterized. Nine hundred and ten co-up-regulated and 737 co-down-regulated genes were identified in the resistant strains. Further analysis showed that 126 co-differentially expressed genes (co-DEGs) (cytochrome P450, carboxy/cholinesterase, glutathione S-transferase, ATP-binding cassette transporter, UDP-glucuronosyl transferase, aminopeptidase N, sialin, serine protease and cuticle protein) may play important roles in indoxacarb resistance in S. litura. In addition, a total of 91 known and 52 novel miRNAs were identified, and 10 miRNAs were co-differentially expressed in the resistant strains of S. litura. Furthermore, 10 co-differentially expressed miRNAs (co-DEmiRNAs) had predicted co-DEGs according to the expected miRNA-mRNA negative regulation pattern and 37 indoxacarb resistance-related co-DEGs were predicted to be the target genes. These results not only broadened our understanding of molecular mechanisms of insecticide resistance by revealing complicated profiles, but also provide important clues for further study on the mechanisms of miRNAs involved in indoxacarb resistance in S. litura.

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