scholarly journals Exosomal MicroRNA-151a-3p Improves the Sensitivity to Radiotherapy via the Interaction between p53 and Histone Deacetylase 5

2021 ◽  
Author(s):  
Seung Min Lee ◽  
Bo Hyun yoon ◽  
Myoung-Hee Kang ◽  
Dong Ha Kim ◽  
Yong-Hee cho ◽  
...  
Keyword(s):  
Radiation Exposure ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Tumor Suppression ◽  
Bioinformatics Analysis ◽  
Radiation Treatment ◽  
Radiation Equipment ◽  
Exosomal Mirna ◽  
Exosomal Microrna

Abstract Background: Tumor-derived exosomal microRNAs are key elements of the cell-cell communications response to lots of stimuli. However, various functions of the exosome in tumor suppression by radiotherapy (RT) are not clearly understood. Our study showed a previously unknown interaction of p53 and histone deacetylase 5 (HDAC5) by radiation exposure in hepatocellular carcinoma (HCC). Methods: Using serial ultracentrifugation methods, radiation and non-radiation exosomes were purified to investigate the radioresistance of miRNA151a-3p. Radiation doses were treated in 2gy and 4gy using radiation equipment X-RAD 320 to observe the expression of HDAC5 and p53 in hepatic cancer cells. Exosomal miRNA bioinformatics analysis was conducted to find a variation in the miRNA configuration inside Exosome after radiation exposure.Results: HDAC5 and p53 interacted by exposure to radiation, which increased exosome release and altered microRNAs' composition within exosomes. Also, we have described the intercommunication occurring between irradiated and untreated cells via exosomal microRNAs that affect tumor proliferation. In particular, the expression of exosomal microR151a-3p was markedly reduced by radiation treatment. We confirmed that inhibition of exosomal microR151a-3p promotes suppression of non-irradiated cancer cells, thereby increasing RT sensitivity. Conclusion: our present findings demonstrated HDAC5 is a key component of the p53-mediated release of exosomes resulting in tumor suppression through exosomal microRNA-151a-3p in response to radiation. Finally, we highlight the important role of exosomal microRNA 151a-3p as a biomarker in enhancing RT sensitivity.

scholarly journals The Role of Exosomal miRNAs in Glioma: Biological Function and Clinical Application

2021 ◽  
Vol 11 ◽  
Author(s):  
Yirizhati Aili ◽  
Nuersimanguli Maimaitiming ◽  
Yusufu Mahemuti ◽  
Hu Qin ◽  
Yongxin Wang ◽  
...  
Keyword(s):  
Theoretical Basis ◽  
Poor Prognosis ◽  
Biological Function ◽  
Treatment Resistance ◽  
Combination Therapies ◽  
Exosomal Mirnas ◽  
Exosomal Mirna ◽  
The Relationship ◽  
Exosomal Microrna

Gliomas are complex and heterogeneous central nervous system tumors with poor prognosis. Despite the increasing development of aggressive combination therapies, the prognosis of glioma is generally unsatisfactory. Exosomal microRNA (miRNA) has been successfully used in other diseases as a reliable biomarker and even therapeutic target. Recent studies show that exosomal miRNA plays an important role in glioma occurrence, development, invasion, metastasis, and treatment resistance. However, the association of exosomal miRNA between glioma has not been systemically characterized. This will provide a theoretical basis for us to further explore the relationship between exosomal miRNAs and glioma and also has a positive clinical significance in the innovative diagnosis and treatment of glioma.

Organization of chromatin in cancer cells: role of signalling pathways

1999 ◽  
Vol 77 (4) ◽  
pp. 265-275 ◽  
Author(s):  
J R Davie ◽  
S K Samuel ◽  
V A Spencer ◽  
L T Holth ◽  
D N Chadee ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Nuclear Matrix ◽  
Nuclear Dna ◽  
Mapk Pathway ◽  
Signalling Pathway ◽  
Signalling Pathways ◽  
Chemical Signalling

The role of mechanical and chemical signalling pathways in the organization and function of chromatin is the subject of this review. The mechanical signalling pathway consists of the tissue matrix system that links together the three-dimensional skeletal networks, the extracellular matrix, cytoskeleton, and nuclear matrix. Intermediate filament proteins are associated with nuclear DNA, suggesting that intermediate filaments may have a role in the organization of chromatin. In human hormone-dependent breast cancer cells, the interaction between cytokeratins and chromatin is regulated by estrogens. Transcription factors, histone acetyltransferases, and histone deacetylases, which are associated with the nuclear matrix, are components of the mechanical signalling pathway. Recently, we reported that nuclear matrix-bound human and chicken histone deacetylase 1 is associated with nuclear DNA in situ, suggesting that histone deacetylase has a role in the organization of nuclear DNA. Chemical signalling pathways such as the Ras/mitogen-activated protein kinase (Ras/MAPK) pathway stimulate the activity of kinases that modify transcription factors, nonhistone chromosomal proteins, and histones. The levels of phosphorylated histones are increased in mouse fibroblasts transformed with oncogenes, the products of which stimulate the Ras/MAPK pathway. Histone phosphorylation may lead to decondensation of chromatin, resulting in aberrant gene expression.Key words: histone acetylation, histone phosphorylation, nuclear matrix, cytoskeleton, histone deacetylase, cancer.

scholarly journals Up-regulation of VANGL1 by IGF2BPs and miR-29b-3p attenuates the detrimental effect of irradiation on lung adenocarcinoma

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Chun-cheng Hao ◽  
Cui-yang Xu ◽  
Xin-yu Zhao ◽  
Jia-ning Luo ◽  
Gang Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Adenocarcinoma ◽  
Mrna Stability ◽  
Adaptive Response ◽  
Detrimental Effect ◽  
Bioinformatics Analysis ◽  
Radiation Treatment ◽  
Lethal Effect ◽  
Downstream Effectors

AbstractAccumulating evidence suggests that radiation treatment causes an adaptive response of lung adenocarcinoma (LUAD), which in turn attenuates the lethal effect of the irradiation. Previous microarray assays manifested the change of gene expression profile after irradiation. Bioinformatics analysis of the significantly changed genes revealed that VANGL1 may notably influence the effect of radiation on LUAD. To determine the role of VANGL1, this study knocked down or overexpressed VANGL1 in LUAD. M6A level of VANGL1 mRNA was determined by M6A-IP-qPCR assay. Irradiation caused the up-regulation of VANGL1 with the increase of VANGL1 m6A level. Depletion of m6A readers, IGF2BP2/3, undermined VANGL1 mRNA stability and expression upon irradiation. miR-29b-3p expression was decreased by irradiation, however VANGL1 is a target of miR-29b-3p which was identified by Luciferase report assay. The reduction of miR-29b-3p inhibited the degradation of VANGL1 mRNA. Knockdown of VANGL1 enhanced the detrimental effect of irradiation on LUAD, as indicated by more severe DNA damage and increased percentage of apoptotic cells. Immunocoprecipitation revealed the interaction between VANGL1 with BRAF. VANGL1 increased BRAF probably through suppressing the protein degradation, which led to the increase of BRAF downstream effectors, TP53BP1 and RAD51. These effectors are involved in DNA repair after the damage. In summary, irradiation caused the up-regulation of VANGL1, which, in turn, mitigated the detrimental effect of irradiation on LUAD by protecting DNA from damage probably through activating BRAF/TP53BP1/RAD51 cascades. Increased m6A level of VANGL1 and reduced miR-29b-3p took the responsibility of VANGL1 overexpression upon irradiation.

The Role of Autophagy in Cancer Radiotherapy

2020 ◽  
Vol 13 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Lei Li ◽  
Wen-Ling Liu ◽  
Lei Su ◽  
Zhou-Cheng Lu ◽  
Xiu-Sheng He
Keyword(s):  
Cancer Cells ◽  
Radiation Treatment ◽  
Cancer Development ◽  
Autophagosome Formation ◽  
Different Types ◽  
Common Strategy ◽  
Multistep Process ◽  
Chaperone Mediated Autophagy ◽  
Catabolic Process

Background: Autophagy, a pathway for lysosomal-mediated cellular degradation, is a catabolic process that recycles intracellular components to maintain metabolism and survival. It is classified into three major types: macroautophagy, microautophagy, and the chaperone-mediated autophagy (CMA). Autophagy is a dynamic and multistep process that includes four stages: nucleation, elongation, autophagosome formation, and fusion. Interestingly, the influence of autophagy in cancer development is complex and paradoxical, suppressive, or promotive in different contexts. Autophagy in cancer has been demonstrated to serve as both a tumour suppressor and promoter. Radiotherapy is a powerful and common strategy for many different types of cancer and can induce autophagy, which has been shown to modulate sensitivity of cancer to radiotherapy. However, the role of autophagy in radiation treatment is controversial. Some reports showed that the upregulation of autophagy was cytoprotective for cancer cells. Others, in contrast, showed that the induction of autophagy was advantageous. Here, we reviewed recent studies and attempted to discuss the various aspects of autophagy in response to radiotherapy of cancer. Thus, we could decrease the viability of cancer cell and increase the sensibility of cancer cells to radiation, providing a new basis for the application of autophagy in clinical tumor radiotherapy

scholarly journals Diphthamide Biosynthesis 1 is a Novel Oncogene in Colorectal Cancer Cells and is Regulated by MiR-218-5p

2017 ◽  
Vol 44 (2) ◽  
pp. 505-514 ◽  
Author(s):  
Minghui Liu ◽  
Kai Yin ◽  
Xu Guo ◽  
Huijin Feng ◽  
Min Yuan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Bioinformatics Analysis ◽  
Inverse Correlation ◽  
Luciferase Reporter ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Colorectal Cancer Cells ◽  
Invasion Assays

Background/Aims: This study focused on the oncogenic role of Diphthamide biosynthesis 1 (DPH1) in colorectal cancer (CRC) cells. Methods: The expression of DPH1 was determined by quantitative RT-PCR analysis and western blotting in CRC tissues. The role of DPH1 in CRC cells was investigated via cell viability and invasion assays under the condition of DPH1 silencing or overexpression. Bioinformatics analysis and luciferase reporter analysis were used to identify the upstream microRNA which might regulate DPH1.The inverse correlation between the microRNA and DPH1 was also detected in CRC cells. Results: We identified an unexpected role for DPH1 as an oncogene in CRC cells. The tumour-suppressive miR-218-5p regulates DPH1 directly and negatively. Loss of miR-218-5p drives the oncogenic role of DPH1 in CRC cells. Conclusion: The modulation of DPH1 by miR-218-5p may be an important regulatory axis during CRCtumourigenesis.

scholarly journals REV1 Inhibition Enhances Radioresistance and Autophagy

2021 ◽  
Author(s):  
Kanayo Ikeh ◽  
Erica Lamkin ◽  
Andrew Crompton ◽  
Jamie Deutsch ◽  
Kira Fisher ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Cancer Cells ◽  
Cell Response ◽  
Radiation Treatment ◽  
Therapy Resistance ◽  
Treatment Regimens ◽  
Response To Chemotherapy ◽  
Enhance Tumor Cell ◽  
Significant Bearing

Cancer therapy resistance is a persistent clinical challenge. Recently, inhibition of the mutagenic translesion synthesis (TLS) protein REV1 was shown to enhance tumor cell response to chemotherapy by triggering senescence hallmarks. These observations suggest REV1’s important role in determining cancer cell response to chemotherapy. Whether REV1 inhibition would similarly sensitize cancer cells to radiation treatment is unknown. This study reports a lack of radiosensitization in response to REV1 inhibition by small molecule inhibitors in ionizing radiation-exposed cancer cells. Instead, REV1 inhibition unexpectedly triggers autophagy, which is a known biomarker of radioresistance. Collectively, we report a possible role of REV1 TLS protein in determining cancer treatment outcomes depending upon the type of DNA damage inflicted. Furthermore, we discover REV1 inhibition directly triggers autophagy, an uncharacterized REV1 phenotype, with significant bearing on cancer treatment regimens.

Role of exosomal microRNA-125b-5p in conferring the metastatic phenotype among pancreatic cancer cells with different potential of metastasis

Life Sciences ◽  
2020 ◽  
Vol 255 ◽  
pp. 117857 ◽  
Author(s):  
Mengwei Wu ◽  
Xiaodong Tan ◽  
Peng Liu ◽  
Yifan Yang ◽  
Yinpeng Huang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Metastatic Phenotype ◽  
Pancreatic Cancer Cells ◽  
Exosomal Microrna

scholarly journals The Role of Gold Nanorods in the Response of Prostate Cancer and Normal Prostate Cells to Ionizing Radiation—In Vitro Model

2020 ◽  
Vol 22 (1) ◽  
pp. 16
Author(s):  
Marika Musielak ◽  
Agnieszka Boś-Liedke ◽  
Igor Piotrowski ◽  
Maciej Kozak ◽  
Wiktoria Suchorska
Keyword(s):  
Ionizing Radiation ◽  
Cancer Cells ◽  
Gold Nanorods ◽  
Cellular Proliferation ◽  
Radiation Treatment ◽  
Normal Prostate ◽  
Prostate Cells ◽  
Vitro Model

To increase the efficiency of therapy via enhancing its selectivity, the usage of gold nanorods (GNR) as a factor sensitizing cancer cells to radiation was proposed. Due to gold nanoparticles’ characteristics, the smaller doses of radiation would be sufficient in the treatment, protecting the healthy tissue around the tumor. The aim of this study was to investigate the effect of gold nanorods on cancer and normal prostate cells and the role of nanorods in the cell response to ionizing radiation. The effect was evaluated by measuring the toxicity, cell cycle, cell granularity, reactive oxygen species (ROS) level, and survival fractions. Nanorods showed a strong toxicity dependent on the concentration and incubation time toward all used cell lines. A slight effect of nanorods on the cycle distribution was observed. The results demonstrated that the administration of nanorods at higher concentrations resulted in an increased level of generated radicals. The results of cellular proliferation after irradiation are ambiguous; however, there are noticeable differences after the application of nanorods before irradiation. The obtained results lead to the conclusion that nanorods affect the physiology of both normal and cancer cells. Nanorods might become a potential tool used to increase the effectiveness of radiation treatment

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