Fractionated Radiation Alters Oncomir and Tumor Suppressor miRNAs in Human Prostate Cancer Cells

John-Aryankalayil, Molykutty; Palayoor, Sanjeewani T.; Makinde, Adeola Y.; Cerna, David; Simone, Charles B.; Falduto, Michael T.; Magnuson, Scott R.; Coleman, C. Norman

doi:10.1667/rr2703.1

Cited by 69 publications

(98 citation statements)

References 55 publications

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“…Higher expression levels of various miR-17-92 cluster miRNAs were significantly associated with a lower overall survival rate in patients with osteosarcoma (11). In addition, a previous study indicated that the miR-17-92 cluster was downregulated following exposure to radiation in prostate cancer LNCaP cells (12). These findings demonstrate the oncogenic role of the miR-17-92 cluster.…”

Section: Introductionsupporting

confidence: 64%

Combinations of elevated tissue miRNA‑17‑92 cluster expression and serum prostate‑specific antigen as potential diagnostic biomarkers for prostate cancer

Feng

Qian

et al. 2017

Oncol Lett

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Abstract. The aim of the present study was to investigate the effectiveness of the miR-17-92 cluster as a disease progression marker in prostate cancer (PCa). Reverse transcription-quantitative polymerase chain reaction analysis was used to detect the microRNA (miR)-17-92 cluster expression levels in tissues from patients with PCa or benign prostatic hyperplasia (BPH), in addition to in PCa and BPH cell lines. Spearman correlation was used for comparison and estimation of correlations between miRNA expression levels and clinicopathological characteristics such as the Gleason score and prostate-specific antigen (PSA). Receiver operating curve (ROC) analysis was performed for evaluation of specificity and sensitivity of miR-17-92 cluster expression levels for discriminating patients with PCa from patients with BPH. Kaplan-Meier analysis was plotted to investigate the predictive potential of miR-17-92 cluster for PCa biochemical recurrence. Expression of the majority of miRNAs in the miR-17-92 cluster was identified to be significantly increased in PCa tissues and cell lines. Bivariate correlation analysis indicated that the high expression of unregulated miRNAs was positively correlated with Gleason grade, but had no significant association with PSA. ROC curves demonstrated that high expression of miR-17-92 cluster predicted a higher diagnostic accuracy compared with PSA. Improved discriminating quotients were observed when combinations of unregulated miRNAs with PSA were used. Survival analysis confirmed a high combined miRNA score of miR-17-92 cluster was associated with shorter biochemical recurrence interval. miR-17-92 cluster could be a potential diagnostic and prognostic biomarker for PCa, and the combination of the miR-17-92 cluster and serum PSA may enhance the accuracy for diagnosis of PCa.

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Section: Introductionsupporting

confidence: 64%

Combinations of elevated tissue miRNA‑17‑92 cluster expression and serum prostate‑specific antigen as potential diagnostic biomarkers for prostate cancer

Feng

Qian

et al. 2017

Oncol Lett

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“…This includes the impact of radiation dose as well as fractionation schedules on stimulating immunity, on immune effector function and survival. This current study builds on previous work from our laboratory (12, 16, 18) and is designed to more fully understand the immune gene induction cascade in tumor cells, in response to 10 Gy single dose or 10 Gy given in 1 Gy fractions (multifractions) in three prostate cancer cell lines, PC3, DU145 and LNCaP.…”

Section: Resultsmentioning

confidence: 99%

“…Data sets were uploaded into the IPA, then mapped to the functional networks available in the Ingenuity Pathway Knowledge Base and ranked by score as described previously (16). …”

Section: Methodsmentioning

confidence: 99%

Defining Molecular Signature of Pro-Immunogenic Radiotherapy Targets in Human Prostate Cancer Cells

et al. 2014

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To understand the impact of clinically relevant radiation therapy (RT) on tumor immune gene expression and to utilize the changes that occur during treatment to improve cancer treatment outcome, we examined how immune response genes are modulated in prostate cancer cells of varying p53 status. LNCaP (p53 wild-type), PC3 (p53 null) and DU145 (p53 mutant) cells received a 10 Gy single dose or 1 Gy × 10 multifractionated radiation dose to simulate hypofractionated and conventionally fractionated prostate radiotherapy. Total RNA was isolated 24 h after multi-fractionated radiation treatment and single-dose treatments and subjected to microarray analysis and later validated by RT-PCR. RT-PCR was utilized to identify total-dose inflection points for significantly upregulated genes in response to multifractionated radiation therapy. Radiation-induced damage-associated molecular pattern molecules (DAMPs) and cytokine analyses were performed using bioluminescence and ELISA. Multifractionated doses activated immune response genes more robustly than single-dose treatment, with a relatively larger number of immune genes upregulated in PC3 compared to DU145 and LNCaP cells. The inflection point of multifractionated radiation-induced immune genes in PC3 cells was observed in the range of 8–10 Gy total radiation dose. Although both multifractionated and single-dose radiation-induced proinflammatory DAMPs and positively modulated the cytokine environment, the changes were of higher magnitude with multifractionated therapy. The findings of this study together with the gene expression data suggest that cells subjected to multifractionated radiation treatment would promote productive immune cell–tumor cell interactions.

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“…5 Through the targeting of specific genes, miRs can behave functionally as tumor suppressors or oncogenes. 6 …”

Section: Introductionmentioning

confidence: 99%

Delivery of Functional Anti-miR-9 by Mesenchymal Stem Cell–derived Exosomes to Glioblastoma Multiforme Cells Conferred Chemosensitivity

Munoz

Bliss

Greco

et al. 2013

Molecular Therapy - Nucleic Acids

437

313

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Glioblastoma multiforme (GBM), the most common and lethal tumor of the adult brain, generally shows chemo- and radioresistance. MicroRNAs (miRs) regulate physiological processes, such as resistance of GBM cells to temozolomide (TMZ). Although miRs are attractive targets for cancer therapeutics, the effectiveness of this approach requires targeted delivery. Mesenchymal stem cells (MSCs) can migrate to the sites of cancers, including GBM. We report on an increase in miR-9 in TMZ-resistant GBM cells. miR-9 was involved in the expression of the drug efflux transporter, P-glycoprotein. To block miR-9, methods were developed with Cy5-tagged anti-miR-9. Dye-transfer studies indicated intracellular communication between GBM cells and MSCs. This occurred by gap junctional intercellular communication and the release of microvesicles. In both cases, anti-miR-9 was transferred from MSCs to GBM cells. However, the major form of transfer occurred with the microvesicles. The delivery of anti-miR-9 to the resistant GBM cells reversed the expression of the multidrug transporter and sensitized the GBM cells to TMZ, as shown by increased cell death and caspase activity. The data showed a potential role for MSCs in the functional delivery of synthetic anti-miR-9 to reverse the chemoresistance of GBM cells.

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Fractionated Radiation Alters Oncomir and Tumor Suppressor miRNAs in Human Prostate Cancer Cells

Cited by 69 publications

References 55 publications

Combinations of elevated tissue miRNA‑17‑92 cluster expression and serum prostate‑specific antigen as potential diagnostic biomarkers for prostate cancer

Combinations of elevated tissue miRNA‑17‑92 cluster expression and serum prostate‑specific antigen as potential diagnostic biomarkers for prostate cancer

Defining Molecular Signature of Pro-Immunogenic Radiotherapy Targets in Human Prostate Cancer Cells

Delivery of Functional Anti-miR-9 by Mesenchymal Stem Cell–derived Exosomes to Glioblastoma Multiforme Cells Conferred Chemosensitivity

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