scholarly journals MiR-148b, MiR-152/ALCAM Axis Regulates the Proliferation and Invasion of Pituitary Adenomas Cells

2017 ◽  
Vol 44 (2) ◽  
pp. 792-803 ◽  
Author(s):  
Wei He ◽  
Ling Huang ◽  
Min Li ◽  
Yue Yang ◽  
Zhen Chen ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Target Genes ◽  
Annexin V ◽  
Expression Level ◽  
Human Pituitary ◽  
Aberrant Expression ◽  
Leukocyte Antigen ◽  
Noninvasive Samples ◽  
Proliferation And Invasion

Background/Aims: Aberrant expression of miRNA has been found in many tumor tissues to regulate the tumorigenesis by binding to the 3`- untranslated region (3`-UTR) of the target genes. The aim of this study is to investigate the role of miR-148b, miR-152/ALCAM axis in human pituitary adenomas (PAs). Methods: First, we detected the expression level of miR-148b-3p and miR-152 in human PAs samples by using qRT-PCR. Then we studied the role of miR-148b-3p, miR-152 on human PAs cell proliferation, invasion and apoptosis by using MTS assay, Transwell invasion assay and Annexin V/PI Staining Test. To study the relationship between miR-148b-3p, miR-152 and activated leukocyte antigen molecule (ALCAM), we overexpressed miR-148-3p or miR-152 by transfecting specific mimics. Lucifearase reporter assay was then performed to confirm the target. Next, we studied the biological functions of ALCAM in human PAs cells. Finally, the role of miR-148b-3p, miR-152/ALCAM axis in PAs cells was studied. Results: The expression level of miR-148-3p and miR-152 in invasive PAs samples was lower than those in noninvasive samples. Overexpression of miR-148b-3p, miR-152 could repress proliferation and invasion, and promote apoptosis. Moreover, miR-148b-3p and miR-152 could repress activated leukocyte antigen molecule (ALCAM) expression. Knockdown of ALCAM could repress proliferation and invasion and promote apoptosis. By contrary, overexpression of ALCAM promoted proliferation and invasion. Further, the rescue experiments indicated that overexpression of ALCAM significantly restored the proliferation, apoptosis, and invasion influenced by miR-148b-3p and miR-152. Conclusions: Our study suggests that miR-148b-3p, miR-152 may serve as suppressors in PAs through downregulating ALCAM expression. miR-148b, miR-152/ ALCAM axis may be a new therapeutic target in the future.

scholarly journals KLF7/VPS35 axis contributes to hepatocellular carcinoma progression through CCDC85C-activated β-catenin pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yarong Guo ◽  
Bao Chai ◽  
Junmei Jia ◽  
Mudan Yang ◽  
Yanjun Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Luciferase Reporter ◽  
Aberrant Expression ◽  
Proliferation And Invasion ◽  
Hcc Cells

Abstract Objective Dysregulation of KLF7 participates in the development of various cancers, but it is unclear whether there is a link between HCC and aberrant expression of KLF7. The aim of this study was to investigate the role of KLF7 in proliferation and migration of hepatocellular carcinoma (HCC) cells. Methods CCK8, colony growth, transwell, cell cycle analysis and apoptosis detection were performed to explore the effect of KLF7, VPS35 and Ccdc85c on cell function in vitro. Xenografted tumor growth was used to assess in vivo role of KLF7. Chip-qPCR and luciferase reporter assays were applied to check whether KLF7 regulated VPS35 at transcriptional manner. Co-IP assay was performed to detect the interaction between VPS35 and Ccdc85c. Immunohistochemical staining and qRT-PCR analysis were performed in human HCC sampels to study the clinical significance of KLF7, VPS35 and β-catenin. Results Firstly, KLF7 was highly expressed in human HCC samples and correlated with patients’ differentiation and metastasis status. KLF7 overexpression contributed to cell proliferation and invasion of HCC cells in vitro and in vivo. KLF7 transcriptional activation of VPS35 was necessary for HCC tumor growth and metastasis. Further, co-IP studies revealed that VPS35 could interact with Ccdc85c in HCC cells. Rescue assay confirmed that overexpression of VPS35 and knockdown of Ccdc85c abolished the VPS35-medicated promotion effect on cell proliferation and invasion. Finally, KLF7/VPS35 axis regulated Ccdc85c, which involved in activation of β-catenin signaling pathway, confirmed using β-catenin inhibitor, GK974. Functional studies suggested that downregulation of Ccdc85c partly reversed the capacity of cell proliferation and invasion in HCC cells, which was regulated by VPS35 upregulation. Lastly, there was a positive correlation among KLF7, VPS35 and active-β-catenin in human HCC patients. Conclusion We demonstrated that KLF7/VPS35 axis promoted HCC cell progression by activating Ccdc85c-medicated β-catenin pathway. Targeting this signal axis might be a potential treatment strategy for HCC.

scholarly journals Epigenetic Regulation of miR-92a and TET2 and Their Association in Non-Hodgkin Lymphoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Esther K. Elliott ◽  
Lloyd N. Hopkins ◽  
Robert Hensen ◽  
Heidi G. Sutherland ◽  
Larisa M. Haupt ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cell Lines ◽  
Target Genes ◽  
Cpg Islands ◽  
Mature Mirnas ◽  
Tumour Suppressor Genes ◽  
Promoter Regions ◽  
Aberrant Expression ◽  
Non Hodgkin Lymphoma

MicroRNAs (miRNAs) are well known for their ability to regulate the expression of specific target genes through degradation or inhibition of translation of the target mRNA. In various cancers, miRNAs regulate gene expression by altering the epigenetic status of candidate genes that are implicated in various difficult to treat haematological malignancies such as non-Hodgkin lymphoma by acting as either oncogenes or tumour suppressor genes. Cellular and circulating miRNA biomarkers could also be directly utilised as disease markers for diagnosis and monitoring of non-Hodgkin lymphoma (NHL); however, the role of DNA methylation in miRNA expression regulation in NHL requires further scientific inquiry. In this study, we investigated the methylation levels of CpGs in CpG islands spanning the promoter regions of the miR-17–92 cluster host gene and the TET2 gene and correlated them with the expression levels of TET2 mRNA and miR-92a-3p and miR-92a-5p mature miRNAs in NHL cell lines, tumour samples, and the whole blood gDNA of an NHL case control cohort. Increased expression of both miR-92a-3p and miR-92a-5p and aberrant expression of TET2 was observed in NHL cell lines and tumour tissues, as well as disparate levels of dysfunctional promoter CGI methylation. Both miR-92a and TET2 may play a concerted role in NHL malignancy and disease pathogenesis.

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 Evaluation the Expression of Efflux Pump Genes “Tap & P55 in Mycobacterium Tuberculosis Clinical Isolates in Fars, Iran

2020 ◽  
Author(s):  
Fardis Khoob ◽  
Milad Shahini Shams Abadi ◽  
Nahal Hadi ◽  
Farzaneh Avazzadeh ◽  
Zahra Zarei
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Target Genes ◽  
Efflux Pump ◽  
Expression Level ◽  
Genetic Mutations ◽  
Antimicrobial Sensitivity ◽  
Probable Role ◽  
Tuberculosis Therapy

Abstract BackgroundThe increasing drug resistance in Mycobacterium tuberculosis isolates has become a global problem for tuberculosis therapy programs. Genetic mutations in rifampin (RIF), one of the key drugs in the treatment of tuberculosis are main mechanism of resistant to this drug in M. tuberculosis. Absence of mutation in target genes, other mechanisms such as efflux pump suggests possible role of drug resistant.The objective of this study was to find out mutations in rpoB genes in rifampin resistant isolates and to compare the expression level of tap and p55 efflux pump genes in non mutated isolates, mutated isolates in rpoB genes and susceptible isolates.MethodsIn this study, antimicrobial sensitivity test on first line drugs was performed on 200 M. tuberculosis isolates, obtained from TB center in Shiraz (IRAN) and genetic mutations were evaluated in rpoB gene in RIF resistant isolates by multiplex PCR, followed expression level evaluated by Real-time PCR.Resultsout of the 200 isolates tested, 23 (34.33%) showed resistant to RIF. 12 of 23 RIF resistant isolates have mutation in rpoB gene, and frequency of mutations in codons 516, 526 and 531 were 3 (25%), 4 (33.33%) and 5 (41.67%) respectively. The expression level of tap and p55 genes was considerably higher in resistant isolates which had no mutation compared to the expression level of genes in the isolates which had mutation in target genes.ConclusionThe accumulating data suggest the probable role of efflux pump in M. tuberculosis drug resistance, the validation of data needs further phenotypic assays of these pumps.

scholarly journals CD26 upregulates proliferation and invasion in keloid fibroblasts through an IGF-1-induced PI3K/AKT/mTOR pathway

2020 ◽  
Vol 8 ◽  
Author(s):  
Yu Xin ◽  
Peiru Min ◽  
Heng Xu ◽  
Zheng Zhang ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Mammalian Target Of Rapamycin ◽  
Underlying Mechanism ◽  
Mtor Pathway ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Aberrant Expression ◽  
Proliferation And Invasion ◽  
Keloid Fibroblasts

Abstract Background Keloid is a fibrotic dermal disease characterized by an abnormal increase in fibroblast proliferation and invasion. These pathological behaviours may be related to the heterogeneity of keloid fibroblasts (KFs); however, because of a lack of effective biomarkers for KFs it is difficult to study the underlying mechanism. Our previous studies revealed that the expansion of CD26+ KFs was responsible for increased keloid proliferation and invasion capabilities; the intrinsic relationship and mechanism between CD26 and keloid is therefore worthy of further investigation. The aim of this study was to explore molecular mechanisms in the process of CD26 upregulated KFs proliferation and invasion abilities, and provide more evidence for CD26 as an effective biomarker of keloid and a new clinical therapeutic target. Methods Flow cytometry was performed to isolate CD26+/CD26− fibroblasts from KFs and normal fibroblasts. To generate stably silenced KFs for CD26 and insulin-like growth factor-1 receptor (IGF-1R), lentiviral particles encoding shRNA targeting CD26 and IGF-1R were used for transfection. Cell proliferations were analysed by cell counting kit-8 assay and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay. Scratching assay and transwell assay were used to assess cell migration and invasion abilities. To further quantify the regulatory role of CD26 expression in the relevant signalling pathway, RT-qPCR, western blot, ELISA, PI3K activity assay and immunofluorescence were used. Results Aberrant expression of CD26 in KFs was proven to be associated with increased proliferation and invasion of KFs. Furthermore, the role of the IGF-1/IGF-1 receptor axis was also studied in CD26 and was found to upregulate KF proliferation and invasion. The PI3K/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway was shown to affect CD26-regulated KF proliferation and invasion by increasing phosphorylation levels of S6 kinase and 4E-binding protein. Conclusions CD26 can be the effective biomarker for KFs, and its expression is closely related to proliferation and invasion in keloids through the IGF-1-induced PI3K/AKT/mTOR pathway. This work provides a novel perspective on the pathological mechanisms affecting KFs and therapeutic strategies against keloids.

Expression of Pit-1 and related proteins in diverse human pituitary adenomas

1993 ◽  
Vol 11 (3) ◽  
pp. 283-290 ◽  
Author(s):  
N Hoggard ◽  
K Callaghan ◽  
A Levy ◽  
J R E Davis
Keyword(s):  
Dna Binding ◽  
Pituitary Adenomas ◽  
Target Genes ◽  
Gene Promoter ◽  
Specific Protein ◽  
Binding Activity ◽  
Mobility Shift ◽  
Human Pituitary ◽  
Dna Binding Activity ◽  
Human Pituitary Adenomas

ABSTRACT Pit-1, a member of the POU family of homeodomain transcription factors, activates prolactin and GH gene expression but also has a role in pituitary cell differentiation and proliferation. Expression of Pit-1 may therefore be of central importance in the function and phenotype of human pituitary adenomas. We have found evidence that, in addition to Pit-1 mRNA, Pit-1-like immunoreactivity and DNA-binding activity are readily detectable in a series of human pituitary adenomas. Gel mobility shift assays using adenoma protein extracts with two Pit-1-binding sites from the human prolactin gene promoter demonstrated the formation of several DNA sequence-specific protein—DNA complexes; some of these could be accounted for by Oct-1-binding activity. Pit-1 activity was anticipated in prolactin- and GH-secreting adenomas, but was also detected in a proportion of endocrine-inactive (non-secreting) adenomas that did not express Pit-1 target genes. The data demonstrate the presence of Pit-1 in a range of pituitary adenomas. Different adenomas generated slightly differing patterns of DNA-binding activity, though Pit-1 mRNA and protein size appeared normal in all tumours so far examined.

scholarly journals Long Noncoding RNA PRNCR1 Reduces Renal Epithelial Cell Apoptosis in Cisplatin-Induced AKI by Regulating miR-182-5p/EZH1

2021 ◽  
Vol 46 (2) ◽  
pp. 162-172
Author(s):  
Jing Li ◽  
Xing Fan ◽  
Qian Wang ◽  
Youlan Gong ◽  
Li Guo
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Target Genes ◽  
Cell Damage ◽  
Kidney Injury ◽  
Annexin V ◽  
Expression Level ◽  
Renal Epithelial Cell

<b><i>Background/Aims:</i></b> This study was designed to examine the role of long noncoding RNA PRNCR1 in cisplatin-induced acute kidney injury (AKI) in vitro and in vivo. <b><i>Methods:</i></b> The expression levels of PRNCR1 and miR-182-5p in cisplatin-induced AKI mice were examined. HK-2 cells were treated with cisplatin to induce cell damage. Then, the effects of PRNCR1 and miR-182-5p on cisplatin-stimulated HK-2 cell viability and apoptosis were detected by the CCK-8 and annexin V-FITC/PI method. Target genes of PRNCR1 and miR-182-5p were analyzed by bioinformatics analysis and luciferase. <b><i>Results:</i></b> The expression level of PRNCR1 was significantly reduced in cisplatin-induced AKI mice. In addition, overexpression of PRNCR1 attenuated the damage of cisplatin to HK-2. The expression level of miR-182-5p was significantly raised in cisplatin-induced AKI mice. MiR-182-5p was negatively regulated by PRNCR1 and leaded to an upregulation of EZH1 expression. Overexpression of PRNCR1 attenuated cisplatin-induced apoptosis by downregulating the miR-182-5p/EZH1 axis. <b><i>Conclusion:</i></b> LncPRNCR1 reduced the apoptosis of renal epithelial cells induced by cisplatin by modulating miR-182-5p/EZH1.

scholarly journals Insights Into the Function and Clinical Application of HDAC5 in Cancer Management

2021 ◽  
Vol 11 ◽  
Author(s):  
Jun Yang ◽  
Chaoju Gong ◽  
Qinjian Ke ◽  
Zejun Fang ◽  
Xiaowen Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Proliferation ◽  
Regulatory Mechanisms ◽  
Biological Functions ◽  
Multiple Cancer ◽  
Aberrant Expression ◽  
Cancer Management ◽  
Cancer Types ◽  
Proliferation And Invasion

Histone deacetylase 5 (HDAC5) is a class II HDAC. Aberrant expression of HDAC5 has been observed in multiple cancer types, and its functions in cell proliferation and invasion, the immune response, and maintenance of stemness have been widely studied. HDAC5 is considered as a reliable therapeutic target for anticancer drugs. In light of recent findings regarding the role of epigenetic reprogramming in tumorigenesis, in this review, we provide an overview of the expression, biological functions, regulatory mechanisms, and clinical significance of HDAC5 in cancer.

Infrequent mutations of p16INK4A and p15INK4B genes in human pituitary adenomas

1997 ◽  
Vol 136 (1) ◽  
pp. 74-80 ◽  
Author(s):  
Katsuhiko Yoshimoto ◽  
Chisato Tanaka ◽  
Shozo Yamada ◽  
Takehiko Kimura ◽  
Hiroyuki Iwahana ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Pituitary Adenomas ◽  
Single Strand Conformation Polymorphism ◽  
Polymorphism Analysis ◽  
Cyclin Dependent Kinase ◽  
Human Pituitary ◽  
Coding Regions ◽  
Polymerase Chain ◽  
Conformation Polymorphism

Abstract The p16INK4A and p15INK4B genes on chromosome 9p21 encode the p16 and p15 inhibitors of cyclin D/cyclin-dependent kinase 4 complexes respectively. Mutations and deletions of the p16INK4A gene have been found in melanomas and many other types of tumors. To assess the role of the p16INK4A and p15INK4B genes in tumorigenesis of the pituitary gland, 31 sporadic pituitary adenomas and 2 pituitary adenomas in familial acrogigantism were examined for loss of heterozygosity on 9p21–22 and screened for mutations in the p16INK4A and p15INK4B genes. To identify pituitary adenomas which had lost which had lost 9p21–22, pituitary adenomas were genotyped with markers flanking the p16INK4A and p15INK4B loci. The frequency of mutations in coding regions of the p16INK4A and the p15INK4B genes in pituitary adenomas was determined with polymerase chain reation-single strand conformation polymorphism analysis and sequencing of variants. Of the 33 pituitary adenomas, two revealed loss of 9p21–22 sequences, but none of them had tumor-specific mutations. We conclude that mutations of the p16INK4A and p15INK4B genes are not required for tumorigenesis of the pituitary gland. European Journal of Endocrinology 136 74–80

scholarly journals Decorin promotes apoptosis and autophagy via suppressing c-Met in HTR-8 trophoblasts

Reproduction ◽  
2020 ◽  
Vol 159 (6) ◽  
pp. 669-677 ◽  
Author(s):  
Yeping Wang ◽  
Hongping Zhang ◽  
Yuehui Zhang ◽  
Xiaoqing Li ◽  
Xianqing Hu ◽  
...  
Keyword(s):  
Prolonged Exposure ◽  
Cell Function ◽  
Annexin V ◽  
Dependent Manner ◽  
Aberrant Expression ◽  
Cellular Processes ◽  
Cell Functions ◽  
Downstream Effectors ◽  
Scratch Wound ◽  
Proliferation And Invasion

Decorin (DCN) regulates a vast array of cellular processes including proliferation, migration, apoptosis, and autophagy, and its aberrant expression has been associated with poor extravillous trophoblasts (EVT) invasion of the uterus, which underlies the occurrence of preeclampsia (PE) and intrauterine growth restriction (IUGR). In this study, we aim to elucidate the molecular mechanism of how the DCN regulates the cell functions through the use of trophoblast cell line, HTR-8. Using a series of cell function assays, including CCK8, RTCA, transwell, scratch-wound assay, and Annexin V staining, we found that DCN suppressed proliferation and invasion, while promoted autophagy and apoptosis of HTR-8 in a dose-dependent manner. Transient stimulation of DCN have increased the activity of c-Met and its downstream effectors – Akt, FAK and m-TOR. However, a prolonged exposure to DCN have significantly downregulated the expression of c-Met, leading to suppression of its downstream effectors. Lentivirus that overexpressed c-Met targeting shRNA was used to knockdown c-Met expression and crizotinib was used to selectively inhibit the kinase activity of c-Met in HTR-8 cells. A combination of DCN and c-Met knockdown/inhibition have reduced the proliferation and invasion in HTR-8 cells; however, DCN-induced autophagy and apoptosis were not synergistically enhanced by c-Met inhibition. In conclusion, DCN promotes autophagy and apoptosis predominantly through downregulating c-Met/Akt/mTOR activity in human trophoblasts.

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