scholarly journals Histone deacetylase (HDAC) 9: versatile biological functions and emerging roles in human cancer

2021 ◽  
Author(s):  
Chun Yang ◽  
Stéphane Croteau ◽  
Pierre Hardy
Keyword(s):  
Histone Deacetylase ◽  
Posttranslational Modifications ◽  
Histone Deacetylases ◽  
Muscle Development ◽  
Target Genes ◽  
Human Cancer ◽  
Expression Patterns ◽  
Aberrant Expression ◽  
Physiological Processes ◽  
Cancer Pathogenesis

Abstract Background HDAC9 (histone deacetylase 9) belongs to the class IIa family of histone deacetylases. This enzyme can shuttle freely between the nucleus and cytoplasm and promotes tissue-specific transcriptional regulation by interacting with histone and non-histone substrates. HDAC9 plays an essential role in diverse physiological processes including cardiac muscle development, bone formation, adipocyte differentiation and innate immunity. HDAC9 inhibition or activation is therefore a promising avenue for therapeutic intervention in several diseases. HDAC9 overexpression is also common in cancer cells, where HDAC9 alters the expression and activity of numerous relevant proteins involved in carcinogenesis. Conclusions This review summarizes the most recent discoveries regarding HDAC9 as a crucial regulator of specific physiological systems and, more importantly, highlights the diverse spectrum of HDAC9-mediated posttranslational modifications and their contributions to cancer pathogenesis. HDAC9 is a potential novel therapeutic target, and the restoration of aberrant expression patterns observed among HDAC9 target genes and their related signaling pathways may provide opportunities to the design of novel anticancer therapeutic strategies.

scholarly journals Comprehensive Analysis of the Histone Deacetylase Gene Family in Chinese Cabbage (Brassica rapa): From Evolution and Expression Pattern to Functional Analysis of BraHDA3

Agriculture ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 244
Author(s):  
Seung Hee Eom ◽  
Tae Kyung Hyun
Keyword(s):  
Functional Analysis ◽  
Brassica Rapa ◽  
Chinese Cabbage ◽  
Stress Responses ◽  
Histone Deacetylases ◽  
Expression Patterns ◽  
Evolutionary Relationship ◽  
Gene Families ◽  
Physiological Processes ◽  
Lysine Residues

Histone deacetylases (HDACs) are known as erasers that remove acetyl groups from lysine residues in histones. Although plant HDACs play essential roles in physiological processes, including various stress responses, our knowledge concerning HDAC gene families and their evolutionary relationship remains limited. In Brassica rapa genome, we identified 20 HDAC genes, which are divided into three major groups: RPD3/HDA1, HD2, and SIR2 families. In addition, seven pairs of segmental duplicated paralogs and one pair of tandem duplicated paralogs were identified in the B. rapa HDAC (BraHDAC) family, indicating that segmental duplication is predominant for the expansion of the BraHDAC genes. The expression patterns of paralogous gene pairs suggest a divergence in the function of BraHDACs under various stress conditions. Furthermore, we suggested that BraHDA3 (homologous of Arabidopsis HDA14) encodes the functional HDAC enzyme, which can be inhibited by Class I/II HDAC inhibitor SAHA. As a first step toward understanding the epigenetic responses to environmental stresses in Chinese cabbage, our results provide a solid foundation for functional analysis of the BraHDAC family.

scholarly journals Development of Coumarin-Based Hydroxamates as Histone Deacetylase Inhibitors with Antitumor Activities

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 717 ◽  
Author(s):  
Na Zhao ◽  
Feifei Yang ◽  
Lina Han ◽  
Yuhua Qu ◽  
Di Ge ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Histone Deacetylase ◽  
Cell Lines ◽  
Histone Deacetylases ◽  
Histone Deacetylase Inhibitors ◽  
Human Cancer ◽  
Immunoblot Analysis ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Human Cancer Cell Lines

Histone deacetylases (HDACs) have been proved to be promising targets for the treatment of cancer, and five histone deacetylase inhibitors (HDACis) have been approved on the market for the treatment of different lymphomas. In our previous work, we designed a series of novel coumarin-containing hydroxamate HDACis, among which compounds 6 and 7 displayed promising activities against tumor growth. Based on a molecular docking study, we further developed 26 additional analogues with the aim to improve activity of designed compounds. Several of these new derivatives not only showed excellent HDAC1 inhibitory effects, but also displayed significant growth inhibitory activities against four human cancer cell lines. Representative compounds, 13a and 13c, showed potent anti-proliferative activities against solid tumor cell lines with IC50 values of 0.36–2.91 µM and low cytotoxicity against Beas-2B and L-02 normal cells. Immunoblot analysis revealed that 13a and 13c dose-dependently increased the acetylation of histone H3 and H4. Importantly, the two compounds displayed much better anti-metastatic effects than SAHA against the MDA-MB-231 cell line. Moreover, 13a and 13c arrested MDA-MB-231 cells at G2/M phase and induced MDA-MB-231 cell apoptosis. Finally, the molecular docking study rationalized the high potency of compound 13c.

scholarly journals miRNAs in Health and Disease: A Focus on the Breast Cancer Metastatic Cascade towards the Brain

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1790 ◽  
Author(s):  
Marta Sereno ◽  
Mafalda Videira ◽  
Imola Wilhelm ◽  
István A. Krizbai ◽  
Maria Alexandra Brito
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Current Knowledge ◽  
Survival Rates ◽  
Breast Cancer Patients ◽  
Aberrant Expression ◽  
Metastatic Cascade ◽  
Physiological Processes ◽  
Breast Cancer Brain Metastasis ◽  
Health And Disease

MicroRNAs (miRNAs) are small non-coding RNAs that mainly act by binding to target genes to regulate their expression. Due to the multitude of genes regulated by miRNAs they have been subject of extensive research in the past few years. This state-of-the-art review summarizes the current knowledge about miRNAs and illustrates their role as powerful regulators of physiological processes. Moreover, it highlights their aberrant expression in disease, including specific cancer types and the differential hosting-metastases preferences that influence several steps of tumorigenesis. Considering the incidence of breast cancer and that the metastatic disease is presently the major cause of death in women, emphasis is put in the role of miRNAs in breast cancer and in the regulation of the different steps of the metastatic cascade. Furthermore, we depict their involvement in the cascade of events underlying breast cancer brain metastasis formation and development. Collectively, this review shall contribute to a better understanding of the uniqueness of the biologic roles of miRNAs in these processes, to the awareness of miRNAs as new and reliable biomarkers and/or of therapeutic targets, which can change the landscape of a poor prognosis and low survival rates condition of advanced breast cancer patients.

Total Platelet Transcriptomics and Its Network Analysis by RNA-Seq and miRNA-Seq and PCA Application in Essential Thrombocythaemia

2020 ◽  
pp. 1-8
Author(s):  
Kyung Chul Moon ◽  
Jeong-An Gim ◽  
Dae Sik Kim ◽  
Chul Won Choi ◽  
Jung Yoon ◽  
...  
Keyword(s):  
Regulatory Network ◽  
Target Genes ◽  
Thrombus Formation ◽  
Myeloproliferative Neoplasms ◽  
Expression Patterns ◽  
Principal Component ◽  
Inverse Correlation ◽  
Essential Thrombocythaemia ◽  
Aberrant Expression ◽  
Healthy Control

Differentiating the aetiology of thrombocytosis is limited yet crucial in patients with essential thrombocythaemia (ET). MicroRNAs (miRNAs) regulate haematopoiesis and lineage commitment; aberrant expression of miRNAs plays an important role in myeloproliferative neoplasms. However, the miRNA profile has been poorly explored in ET patients compared to patients with reactive thrombocytosis (RT). A total of 9 samples, including 5 ET patient samples, 2 RT patient samples, and 2 healthy control samples, were analysed in this study. We produced 81.43 million reads from transcripts and 59.60 million reads from small RNAs. We generated a comprehensive miRNA-mRNA regulatory network and identified unique 14 miRNA expression patterns associated with ET. Among the 14 miRNAs, miR-1268a was downregulated in ET and showed an inverse correlation with its 8 putative target genes, including genes associated with thrombus formation and platelet activation (<i>CDH6, EHD2, FUT1, KIF26A, LINC00346, PTPRN, SERF1A,</i> and <i>SLC6A9</i>). Principal component analysis (PCA) showed ET and non-ET groups well clustered in space, suggesting each group had a distinctive expression pattern of mRNAs and miRNAs. These results suggest that the significant dysregulation of miR-1268a and its 8 target genes could be a unique expression of platelet mi­RNAs and miRNA/mRNA regulatory network in ET patients.

scholarly journals Role of miR-10b-5p in the prognosis of breast cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7728 ◽  
Author(s):  
Junmin Wang ◽  
Yanyun Yan ◽  
Zhiqi Zhang ◽  
Yali Li
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Cancer Development ◽  
Clinicopathological Parameters ◽  
Aberrant Expression ◽  
Expression Levels ◽  
Ppi Networks

Breast cancer is the leading cause of cancer-related death in women worldwide. Aberrant expression levels of miR-10b-5p in breast cancer has been reported while the molecular mechanism of miR-10b-5p in tumorigenesis remains elusive. Therefore, this study was aimed to investigate the role of miR-10b-5p in breast cancer and the network of its target genes using bioinformatics analysis. In this study, the expression profiles and prognostic value of miR-10b-5p in breast cancer were analyzed from public databases. Association between miR-10b-5p and clinicopathological parameters were analyzed by non-parametric test. Moreover, the optimal target genes of miR-10b-5p were obtained and their expression patterns were examined using starBase and HPA database. Additionally, the role of these target genes in cancer development were explored via Cancer Hallmarks Analytics Tool (CHAT). The protein–protein interaction (PPI) networks were constructed to further investigate the interactive relationships among these genes. Furthermore, GO, KEGG pathway and Reactome pathway analyses were carried out to decipher functions of these target genes. Results demonstrated that miR-10b-5p was down-regulated in breast cancer and low expression of miR-10b-5p was significantly correlated to worse outcome. Five genes, BIRC5, E2F2, KIF2C, FOXM1, and MCM5, were considered as potential key target genes of miR-10b-5p. As expected, higher expression levels of these genes were observed in breast cancer tissues than in normal tissues. Moreover, analysis from CHAT revealed that these genes were mainly involved in sustaining proliferative signaling in cancer development. In addition, PPI networks analysis revealed strong interactions between target genes. GO, KEGG, and Reactome pathway analysis suggested that these target genes of miR-10b-5p in breast cancer were significantly involved in cell cycle. Predicted target genes were further validated by qRT-PCR analysis in human breast cancer cell line MDA-MB-231 transfected with miR-10b mimic or antisense inhibitors. Taken together, our data suggest that miR-10b-5p functions to impede breast carcinoma progression via regulation of its key target genes and hopefully serves as a potential diagnostic and prognostic marker for breast cancer.

scholarly journals Aberrant Expression of miR-1301 in Human Cancer

2022 ◽  
Vol 11 ◽  
Author(s):  
Chenming Zhong ◽  
Yiyao Dong ◽  
Qiudan Zhang ◽  
Chunhui Yuan ◽  
Shiwei Duan
Keyword(s):  
Signaling Pathways ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Target Genes ◽  
Human Cancer ◽  
Aberrant Expression ◽  
Cerna Network ◽  
Abnormal Expression ◽  
Cisplatin Sensitivity

miR-1301 is a newly discovered miRNA, which is abnormally expressed in 14 types of tumors. miR-1301 inhibits 23 target genes, forms a ceRNA network with 2 circRNAs and 8 lncRNAs, and participates in 6 signaling pathways, thereby affecting tumor cell proliferation, invasion, metastasis, apoptosis, angiogenesis, etc. Abnormal expression of miR-1301 is often associated with poor prognosis of cancer patients. In addition, miR-1301 is related to the anti-tumor effect of epirubicin on osteosarcoma and imatinib on chronic myeloid leukemia(CML) and can enhance the cisplatin sensitivity of ovarian cancer. This work systematically summarizes the abnormal expression and prognostic value of miR-1301 in a variety of cancers, depicts the miR-1301-related signaling pathways and ceRNA network, and provides potential clues for future miR-1301 research.

miR-193b-3p Promotes Proliferation of Goat Myoblast Through Directly Targeting IGF2BP1 and Activating Its Transcription

2020 ◽  
Author(s):  
Li Li ◽  
Xiao Zhang ◽  
Hailong Yang ◽  
Xiaoli Xu ◽  
Yuan Chen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Target Genes ◽  
Expression Patterns ◽  
Muscle Disease ◽  
Cell Counting ◽  
C2c12 Myoblast ◽  
Recognition Element ◽  
Myoblast Proliferation ◽  
The Impact

Abstract BackgroundAs a well-known cancer-related miRNA, miR-193b-3p is enriched in skeletal muscle but dysregulated in muscle disease. However, mechanism underpinning has not been addressed so far. MethodsHere, we probed the impact of miR-193b-3p on myogenesis by mainly using goat tissues and skeletal muscle satellite cells (MuSCs), with combined methods including RNA-seq to profile the transcriptome affected by miR-193b-3p, cell-counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) for cell proliferation assay, and RNA-RNA dual-labeled fluorescence in situ hybridization (FISH) for RNA colocalization. ResultsmiR-193b-3p is highly enriched in goat skeletal muscles, and ectopic miR-193b-3p promotes MuSCs proliferation and differentiation. Moreover, insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) is the most activated insulin signaling genes when overexpression miR-193b-3p and the miRNA recognition element (MRE) within IGF1BP1 3ʹ untranslated region (UTR) is indispensable for its activation caused by miR-193b-3p. Consistently, expression patterns and function of IGF2BP1 were similar to those of miR-193b-3p in tissues and MuSCs. While the overexpression of miR-193b-3p failed to induce pax7 expression and myoblast proliferation when IGF2BP1 knockdown. Furthermore, miR-193b-3p destabilized IGF2BP1 mRNA but unexpectedly promoted levels of IGF2BP1 heteronuclear RNA (hnRNA) dramatically. Moreover, miR-193b-3p could enhance fly luciferase activity when inserted upstream of its promoter, and induce neighboring genes of itself. However, miR-193b-3p inversely regulated IGF2BP1 and myoblast proliferation in mouse C2C12 myoblast. These data unveil that goat miR-193b-3p promotes myoblast proliferation via activating IGF2BP1 by binding on its 3ʹ UTR.ConclusionsOur novel findings highlight the positive regulation between miRNA and its target genes in muscle development, which further extends the repertoire of miRNA functions.

scholarly journals The Role and Function of microRNA in the Pathogenesis of Multiple Myeloma

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1738 ◽  
Author(s):  
Hiroshi Handa ◽  
Yuki Murakami ◽  
Rei Ishihara ◽  
Kei Kimura-Masuda ◽  
Yuta Masuda
Keyword(s):  
Multiple Myeloma ◽  
Messenger Rna ◽  
Target Genes ◽  
Expression Patterns ◽  
Mirna Regulation ◽  
Coding Regions ◽  
Cancer Pathogenesis ◽  
Regulation Mechanisms ◽  
And Function ◽  
Role And Function

Recently, attention has been drawn to the role of non-coding regions of the genome in cancer pathogenesis. MicroRNAs (miRNAs) are small non-coding RNAs with 19–25 bases of length that control gene expression by destroying messenger RNA or inhibiting its translation. In multiple myeloma (MM), the expression of several miRNAs, such as miR-15a and miR-16, is markedly decreased and their target genes upregulated, suggesting their role as tumor-suppressing miRNAs. In contrast, miRNAs such as miR-21 and miR-221 are highly expressed and function as oncogenes (oncomiRs). In addition, several miRNAs, such as those belonging to the miR-34 family, are transcriptional targets of p53 and mediate its tumor-suppressive functions. Many miRNAs are associated with drug resistance, and the modulation of their expression or activity might be explored to reverse it. Moreover, miRNA expression patterns in either MM cells or serum exosomes have been shown to be good prognostic markers. miRNA regulation mechanisms have not been fully elucidated. Many miRNAs are epigenetically controlled by DNA methylation and histone modification, and others regulate the expression of epigenetic modifiers, indicating that miRNA and other epigenetic effectors are part of a network. In this review, we outlined the roles of miRNAs in MM and their potential to predict MM prognosis and develop novel therapies.

scholarly journals Potential role of miR-155-5p in fat deposition and skeletal muscle development of chicken

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Sifan Xu ◽  
Yang Chang ◽  
Guanxian Wu ◽  
Wanting Zhang ◽  
Chaolai Man
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Target Genes ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Fat Deposition ◽  
Skeletal Muscle Development ◽  
Stem Loop ◽  
Related Target ◽  
Kegg Pathways

Abstract miR-155 has multiple functions in many physiological and pathological processes. However, little is known about the expression characteristics of avian miR-155. In the present study, partial pri-miR-155 sequences were cloned from AA+ broiler, Sanhuang broiler and Hy-Line Brown layer, respectively. Stem–loop qRT-PCR was performed to detect the miR-155-5p spatiotemporal expression profiles of each chicken breed, and the target genes of miR-155-5p were predicted in Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results showed that the partial pri-miR-155 sequences of different breeds of chicken were high conserved. The expression patterns of miR-155-5p between broiler and layer were basically similar, and miR-155-5p was expressed highly in immune related tissues (spleen, thymus and bursa). In the same old chicken (14 days old), miR-155-5p expression activity of fat tissue all had higher level in the three chicken breeds, but the expression activities in skeletal muscle of broilers were significantly lower than that of layer (P&lt;0.05). In different development stages of Hy-Line Brown layer, miR-155-5p expression activities in skeletal muscle of 14-day-old and 10-month-old layers were significantly lower than that of 24-month-old layer (P&lt;0.05). Fat related target genes (ACOX1, ACOT7, FADS1, SCD and HSD17B12) and skeletal muscle related target genes (CCNT2, DMD, CFL2, MAPK14, FLNB, ZBTB18 and CDK5) of miR-155-5p were predicted, respectively. The results indicate that miR-155-5p may be an important factor inhibiting the fat deposition and skeletal muscle development in chicken.

Genes Regulated by NPM-ALK Fusion Kinase Play a Key Role in the Activation of AP-1 Transcription Factors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 245-245 ◽  
Author(s):  
Philipp B. Staber ◽  
Werner Linkesch ◽  
Silvia Schauer ◽  
Gerit Moser ◽  
Marshall E. Kadin ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Cell Lines ◽  
Target Genes ◽  
Expression Patterns ◽  
Cdna Libraries ◽  
Cdna Clones ◽  
Anaplastic Lymphoma ◽  
Cancer Pathogenesis ◽  
293 Cells ◽  
Alk Positive

Abstract Background: About half of nodal anaplastic large cell lymphomas (ALCL) express the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) fusion protein, which is the product of a t(2;5)(p23;q35) chromosomal translocation. Expression of this protein has been shown to result in neoplastic change. Combining suppression subtractive hybridization (SSH) and cDNA microarray analysis we aimed at elucidating the consequences of NPM-ALK expression. Methods: SSH cDNA libraries were constructed using mRNA from human embryonic kidney (293) cells transfected with active or kinase-dead NPM-ALK constructs, as well as pools of NPM-ALK positive and negative ALCL cell lines. The resulting cDNA clones and genes relevant for cancer pathogenesis were spotted, generating specific cDNA microarrays comprising 4992 genes. mRNA expression patterns were analyzed in individual cell lines. Real time quantitative RT-PCR of 20 selected genes validated the mRNA expression data of the microarrays. Results: Expression of a set of 102 genes distinguishes NPM-ALK-negative (FE-PD, MAC-2A) from NPM-ALK-positive ALCL cell lines (SU-DHL-1, JB-6, SUP-M2, SR-786, DEL and Karpas 299). The majority are involved in regulation of cell cycle and apoptosis. 38 of these genes also discriminate 293 cells with respect to their NPM-ALK expression. Interestingly, AP-1 target genes, such as GM-CSFRA, GM-CSFRB, ARF5, FAS, FASL, and BCL3, are increased in NPM-ALK expressing cell lines. Electrophoretic mobility shift assay (EMSA) verifies NPM-ALK dependent AP-1 DNA binding activity. Conclusion: This study reveals genes specifically regulated by NPM-ALK lymphoma kinase. Further, we demonstrate that AP-1 activation is a critical target of NPM-ALK signalling.

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