Lactase Decline in Weaning Rats Is Regulated at the Transcriptional Level and Not Caused by Termination of Milk Ingestion

SummaryTissue factor (TF) is a transmembrane receptor which, in association with factors VII and Vila, activates factor IX and X, thereby activating the coagulation protease cascades. In response to bacterial lipopolysaccharide (LPS) monocytes transcribe, synthesize and express TF on their surface. We investigated whether LPS-induced TF in human monocytes is mediated by protein kinase C (PKC) activation. The PKC agonists phorbol 12- myristate 13-acetate (PMA) and phorbol 12, 13 dibutyrate (PdBu) were both potent inducers of TF in human monocytes, whereas 4 alpha-12, 13 didecanoate (4 a-Pdd) had no such effect. Both LPS- and PMA-induced TF activity were inhibited, in a concentration dependent manner, by three different PKC inhibitors: H7, staurosporine and calphostin C. TF antigen determination confirmed that LPS-induced cell-surface TF protein levels decreased in parallel to TF functional activity under staurosporine treatment. Moreover, Northern blot analysis of total RNA from LPS- or PMA-stimulated monocytes showed a concentration-dependent decrease in TF mRNA levels in response to H7 and staurosporine. The decay rate of LPS-induced TF mRNA evaluated after the arrest of transcription by actinomycin D was not affected by the addition of staurosporine, suggesting that its inhibitory effect occurred at a transcriptional level. We conclude that LPS-induced production of TF and its mRNA by human monocytes are dependent on PKC activation.

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CARP Plays a Key Role in Cellular Growth Under Hypertrophic Stimuli in Neonatal Rat Ventricular Myocytes

Vanderbilt Undergraduate Research Journal ◽

10.15695/vurj.v9i0.3790 ◽

2013 ◽

Vol 9 ◽

Author(s):

Tara A Shrout

Keyword(s):

Gene Expression ◽

Ventricular Myocytes ◽

Cellular Growth ◽

Neonatal Rat ◽

Transcriptional Level ◽

Dual Nature ◽

Hypertrophic Growth ◽

Rat Ventricular Myocytes ◽

Neonatal Rat Ventricular Myocytes ◽

Over Time

Cardiac hypertrophy is a growth process that occurs in response to stress stimuli or injury, and leads to the induction of several pathways to alter gene expression. Under hypertrophic stimuli, sarcomeric structure is disrupted, both as a consequence of gene expression and local changes in sarcomeric proteins. Cardiac-restricted ankyrin repeat protein (CARP) is one such protein that function both in cardiac sarcomeres and at the transcriptional level. We postulate that due to this dual nature, CARP plays a key role in maintaining the cardiac sarcomere. GATA4 is another protein detected in cardiomyocytes as important in hypertrophy, as it is activated by hypertrophic stimuli, and directly binds to DNA to alter gene expression. Results of GATA4 activation over time were inconclusive; however, the role of CARP in mediating hypertrophic growth in cardiomyocytes was clearly demonstrated. In this study, Neonatal Rat Ventricular Myocytes were used as a model to detect changes over time in CARP and GATA4 under hypertrophic stimulation by phenylephrine and high serum media. Results were detected by analysis of immunoblotting. The specific role that CARP plays in mediating cellular growth under hypertrophic stimuli was studied through immunofluorescence, which demonstrated that cardiomyocyte growth with hypertrophic stimulation was significantly blunted when NRVMs were co-treated with CARP siRNA. These data suggest that CARP plays an important role in the hypertrophic response in cardiomyocytes.

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Regulation of gene expression during spermatogenesis at transcriptional level

Hereditas (Beijing) ◽

10.3724/sp.j.1005.2011.01300 ◽

2011 ◽

Vol 33 (12) ◽

pp. 1300-1307

Author(s):

Xiu-Jun ZHANG ◽

Mei-Ling LIU ◽

Meng-Chun JIA

Keyword(s):

Gene Expression ◽

Regulation Of Gene Expression ◽

Transcriptional Level

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UBE2L6 is Involved in Cisplatin Resistance by Regulating the Transcription of ABCB6

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200424130934 ◽

2020 ◽

Vol 20 (12) ◽

pp. 1487-1496 ◽

Cited By ~ 1

Author(s):

Midori Murakami ◽

Hiroto Izumi ◽

Tomoko Kurita ◽

Chiho Koi ◽

Yasuo Morimoto ◽

...

Keyword(s):

Gene Expression ◽

Promoter Activity ◽

Anticancer Agent ◽

Cisplatin Resistance ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Molecular Target ◽

Transcriptional Level ◽

And Control ◽

Resistant Cells

Background: Cisplatin is an important anticancer agent in cancer chemotherapy, but when resistant cells appear, treatment becomes difficult, and the prognosis is poor. Objective: In this study, we investigated the gene expression profile in cisplatin sensitive and resistant cells, and identified the genes involved in cisplatin resistance. Methods: Comparison of gene expression profiles revealed that UBE2L6 mRNA is highly expressed in resistant cells. To elucidate whether UBE2L6 is involved in the acquisition of cisplatin resistance, UBE2L6- overexpressing cells established from cisplatin-sensitive cells and UBE2L6-silenced cells developed from cisplatin- resistant cells were generated, and the sensitivity of cisplatin was examined. Results: The sensitivity of the UBE2L6-overexpressing cells did not change compared with the control cells, but the UBE2L6-silenced cells were sensitized to cisplatin. To elucidate the mechanism of UBE2L6 in cisplatin resistance, we compared the gene expression profiles of UBE2L6-silenced cells and control cells and found that the level of ABCB6 mRNA involved in cisplatin resistance was decreased. Moreover, ABCB6 promoter activity was partially suppressed in UBE2L6-silenced cells. Conclusion: These results suggest that cisplatin-resistant cells have upregulated UBE2L6 expression and contribute to cisplatin resistance by regulating ABCB6 expression at the transcriptional level. UBE2L6 might be a molecular target that overcomes cisplatin resistance.

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Influence of cellular metabolites on RNA and protein syntheses by Xanthium nuclei of different developmental phases

Canadian Journal of Botany ◽

10.1139/b86-386 ◽

1986 ◽

Vol 64 (12) ◽

pp. 2922-2927

Author(s):

A. Jana ◽

S. P. Sen

Keyword(s):

Rna Synthesis ◽

Supernatant Fraction ◽

Xanthium Strumarium ◽

Low Molecular Weight ◽

Transcriptional Level ◽

Protein Patterns ◽

Rna Molecules ◽

Reproductive Tissues ◽

Developmental Phases ◽

Vegetative Leaf

Leaf nuclei of vegetative and reproductive plants of Xanthium strumarium L. were incubated with the postribosomal supernatant of either phase and changes at the transcriptional level were studied in homologous and heterologous combinations. In the presence of the supernatant of reproductive plants, RNA synthesis by vegetative nuclei was decreased by 25%. Reproductive nuclei were less active in RNA synthesis. Gel electrophoretic studies revealed four RNA bands in vegetative nuclei incubated with reproductive supernatant, including a fast-moving low molecular weight band that could not be detected when the "vegetative" supernatant was used. The adenine/uracil ratios of the newly synthesized RNA of vegetative nuclei treated with vegetative and reproductive supernatants were 1.46 and 1.54, respectively, compared with 1.15 and 1.04 in the reproductive nuclei. Competitive DNA–RNA hybridization experiments indicated that about 2% of the [3H]RNA synthesized by nuclei of vegetative plants in the presence of the supernatant of reproductive plants could not be beaten out by the RNA of vegetative plants. Small quantitative differences, thus, may be expected in the RNA molecules synthesized by nuclei in the presence of the supernatant fraction of vegetative and reproductive plants. The supernatant fraction of the reproductive tissues decreased the incorporation of [3H]alanine and [3H]leucine in both the buffer-soluble and acid-soluble proteins and the nuclei of vegetative plants were more active in protein synthesis. Protein patterns as studied by acrylamide gel electrophoresis revealed alterations when vegetative leaf nuclei were incubated with the supernatant of reproductive tissues.

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Delivery of Cas13a/crRNA by self-degradable black phosphorus nanosheets to specifically inhibit Mcl-1 for breast cancer therapy

Journal of Materials Chemistry B ◽

10.1039/d0tb01914c ◽

2020 ◽

Vol 8 (48) ◽

pp. 11096-11106

Author(s):

Huahua Yue ◽

Ru Huang ◽

Yuanyue Shan ◽

Da Xing

Keyword(s):

Breast Cancer ◽

Cancer Therapy ◽

Black Phosphorus ◽

Endosomal Escape ◽

Transcriptional Level ◽

Breast Cancer Therapy

The constructed Cas13a/crRNA complex is delivered into cytoplasm by PBP via endocytosis, followed by endosomal escape based on biodegradation of the PBP, and efficiently knocked down Mcl-1 at transcriptional level for breast cancer therapy.

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Aberrantly high activation of a FoxM1–STMN1 axis contributes to progression and tumorigenesis in FoxM1-driven cancers

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-020-00396-0 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Jun Liu ◽

Jipeng Li ◽

Ke Wang ◽

Haiming Liu ◽

Jianyong Sun ◽

...

Keyword(s):

Cell Proliferation ◽

Poor Prognosis ◽

Soft Agar ◽

Transcriptional Level ◽

Regulation Mechanism ◽

Strong Positive Correlation ◽

Cell Viability Assay ◽

High Level

AbstractFork-head box protein M1 (FoxM1) is a transcriptional factor which plays critical roles in cancer development and progression. However, the general regulatory mechanism of FoxM1 is still limited. STMN1 is a microtubule-binding protein which can inhibit the assembly of microtubule dimer or promote depolymerization of microtubules. It was reported as a major responsive factor of paclitaxel resistance for clinical chemotherapy of tumor patients. But the function of abnormally high level of STMN1 and its regulation mechanism in cancer cells remain unclear. In this study, we used public database and tissue microarrays to analyze the expression pattern of FoxM1 and STMN1 and found a strong positive correlation between FoxM1 and STMN1 in multiple types of cancer. Lentivirus-mediated FoxM1/STMN1-knockdown cell lines were established to study the function of FoxM1/STMN1 by performing cell viability assay, plate clone formation assay, soft agar assay in vitro and xenograft mouse model in vivo. Our results showed that FoxM1 promotes cell proliferation by upregulating STMN1. Further ChIP assay showed that FoxM1 upregulates STMN1 in a transcriptional level. Prognostic analysis showed that a high level of FoxM1 and STMN1 is related to poor prognosis in solid tumors. Moreover, a high co-expression of FoxM1 and STMN1 has a more significant correlation with poor prognosis. Our findings suggest that a general FoxM1-STMN1 axis contributes to cell proliferation and tumorigenesis in hepatocellular carcinoma, gastric cancer and colorectal cancer. The combination of FoxM1 and STMN1 can be a more precise biomarker for prognostic prediction.

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MiRNA10b-directed nanotherapy effectively targets brain metastases from breast cancer

Scientific Reports ◽

10.1038/s41598-021-82528-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Byunghee Yoo ◽

Alana Ross ◽

Pamela Pantazopoulos ◽

Zdravka Medarova

Keyword(s):

Breast Cancer ◽

Rna Interference ◽

Lymph Nodes ◽

Therapeutic Effect ◽

Metastatic Breast ◽

Treatment Modalities ◽

Transcriptional Level ◽

Metastatic Progression ◽

Therapeutic Modalities ◽

Metastatic Colonization

AbstractRNA interference represents one of the most appealing therapeutic modalities for cancer because of its potency, versatility, and modularity. Because the mechanism is catalytic and affects the expression of disease-causing antigens at the post-transcriptional level, only small amounts of therapeutic need to be delivered to the target in order to exert a robust therapeutic effect. RNA interference is also advantageous over other treatment modalities, such as monoclonal antibodies or small molecules, because it has a much broader array of druggable targets. Finally, the complementarity of the genetic code gives us the opportunity to design RNAi therapeutics using computational, rational approaches. Previously, we developed and tested an RNAi-targeted therapeutic, termed MN-anti-miR10b, which was designed to inhibit the critical driver of metastasis and metastatic colonization, miRNA-10b. We showed in animal models of metastatic breast cancer that MN-anti-miR10b accumulated into tumors and metastases in the lymph nodes, lungs, and bone, following simple intravenous injection. We also found that treatment incorporating MN-anti-miR10b was effective at inhibiting the emergence of metastases and could regress already established metastases in the lymph nodes, lungs, and bone. In the present study, we extend the application of MN-anti-miR10b to a model of breast cancer metastatic to the brain. We demonstrate delivery to the metastatic lesions and obtain evidence of a therapeutic effect manifested as inhibition of metastatic progression. This investigation represents an additional step towards translating similar RNAi-targeted therapeutics for the systemic treatment of metastatic disease.

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miR-29a sensitizes the response of glioma cells to temozolomide by modulating the P53/MDM2 feedback loop

Cellular & Molecular Biology Letters ◽

10.1186/s11658-021-00266-9 ◽

2021 ◽

Vol 26 (1) ◽

Author(s):

Qiudan Chen ◽

Weifeng Wang ◽

Shuying Chen ◽

Xiaotong Chen ◽

Yong Lin

Keyword(s):

Molecular Mechanism ◽

Feedback Loop ◽

Glioma Cells ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Transcriptional Level ◽

Aberrant Expression ◽

Altered Expression ◽

P53 Signaling

AbstractRecently, pivotal functions of miRNAs in regulating common tumorigenic processes and manipulating signaling pathways in brain tumors have been recognized; notably, miR‐29a is closely associated with p53 signaling, contributing to the development of glioma. However, the molecular mechanism of the interaction between miR-29a and p53 signaling is still to be revealed. Herein, a total of 30 glioma tissues and 10 non-cancerous tissues were used to investigate the expression of miR‐29a. CCK-8 assay and Transwell assay were applied to identify the effects of miR-29a altered expression on the malignant biological behaviors of glioma cells in vitro, including proliferation, apoptosis, migration and invasion. A dual-luciferase reporter assay was used to further validate the regulatory effect of p53 or miR-29a on miR-29a or MDM2, respectively, at the transcriptional level. The results showed that miR-29a expression negatively correlated with tumor grade of human gliomas; at the same time it inhibited cell proliferation, migration, and invasion and promoted apoptosis of glioma cells in vitro. Mechanistically, miR-29a expression was induced by p53, leading to aberrant expression of MDM2 targeted by miR-29a, and finally imbalanced the activity of the p53-miR-29a-MDM2 feedback loop. Moreover, miR-29a regulating p53/MDM2 signaling sensitized the response of glioma cells to temozolomide treatment. Altogether, the study demonstrated a potential molecular mechanism in the tumorigenesis of glioma, while offering a possible target for treating human glioma in the future.

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Methylobacterium oryzae Influences Isoepoxydon Dehydrogenase Gene Expression and Patulin Production by Penicillium expansum

Water ◽

10.3390/w13101427 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1427

Author(s):

Tiago Barros Afonso ◽

Lúcia Chaves Simões ◽

Nelson Lima

Keyword(s):

Gene Expression ◽

Distribution Systems ◽

Water Distribution ◽

Penicillium Expansum ◽

Transcriptional Level ◽

Positive Trend ◽

Mrna Levels ◽

Expression Levels ◽

Production Values ◽

Methylobacterium Oryzae

Biofilms can be considered the main source of microorganisms in drinking water distribution systems (DWDS). The ecology of a biofilm is dependent on a variety of factors, including the presence of microbial metabolites excreted by its inhabitants. This study reports the effect of the Gram-negative bacteria Methylobacterium oryzae on the idh gene expression levels and patulin production of Penicillium expansum mature biofilms. For this purpose, a RT-qPCR method to quantify idh mRNA levels was applied. In addition, the idh expression levels were compared with the patulin production. The results obtained revealed that the effect of the bacterium on pre-established P. expansum biofilms is dependent on the time of interaction. More mature P. expansum biofilms appear to be more resistant to the inhibitory effect that M. oryzae causes towards idh gene expression and patulin production. A positive trend was observed between the idh expression and patulin production values. The results indicate that M. oryzae affects patulin production by acting at the transcriptional level of the idh gene.

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