Distinct microRNA Expression Profiles in Mouse Renal Cortical Tissue after 177Lu-octreotate Administration

Schüler, Emil; Parris, Toshima Z.; Helou, Khalil; Forssell-Aronsson, Eva

doi:10.1371/journal.pone.0112645

Cited by 7 publications

(8 citation statements)

References 48 publications

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“…As previously described, its expression significantly increased in patients responding to preoperative chemoradiotherapy in advanced rectal cancer [20]. Indeed, it is likely that miR-194 expression can depend on radiation doses (7 Gy in our experiments), since it is already known to be regulated at high absorbed doses used for the treatment of neuroendocrine cancers [21]. The expression of miR-194 is clearly correlated with a tumor suppressor function in various cancers including hepatocarcinoma in which it regulates PTBP1 expression involved in tumor proliferation and migration, but also in glioblastoma [22,23].…”

Section: Discussionsupporting

confidence: 61%

Radiotherapy induces specific miRNA expression profiles in glioblastoma exosomes

Boukredine

Saada

Durand

et al. 2021

Preprint

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Background: Glioblastoma (GBM) is the most aggressive and frequent primary brain tumor during adulthood. One of the major treatments is the association of surgery and a combination of chemo and radiotherapies. Despite its immediate efficiency, it fails to prevent the cancer recurrence in the irradiated area due to radioresistance mechanisms. MicroRNAs (miRNAs or miR) are small non-coding, single strand RNA molecules encoding to various specific genes and able to regulate their expression and induce the tumor cell survival leading to radioresistance. Small extracellular vesicles (EVs), or exosomes released by tumor cells in tumor microenvironment and blood circulation are able to transport and diffuse miRNAs and affect the microenvironment by spreading the miRNAs, which drive radioresistance. Aims: i)- To identify the variations of miRNAs expression induced by irradiation in human glioblastoma U87-MG cells and their secreted exosomes collected in supernatants. ii)- To analyze the miRNAs variations in EVs-derived from the plasma of patients during radiotherapy, in order to identify a miRNA signature induced by radiotherapy in a liquid biopsy. Materiel and methods: U87-MG cells were cultured on plates and exposed to irradiation. miRNAs analyzes were performed in cells and in EVs isolated from cell supernatants to determine miRNAs expressions both in cells and in secreted exosomes before and after irradiation. Plasma-derived EVs were collected from 4 glioblastoma patients before and after surgery and radiotherapy treatments. Conclusion: The analysis of miRNAs expression profiles in both GBM cells and their derived EVs revealed that miR profile changes after irradiation. However, the number of similar miR between cells or EVs, following cell irradiation, was restricted to 3 miRs alone suggesting that the irradiation-induced changes in the miR profile in the cells and their EVs are not closely linked. In this context, the miR profile in EVs from patients plasma was investigated to establish a potential link with the miRNAs profile observed in EVs from irradiated cells and to assess its relationship with the response to radiotherapy. Three miRs (different from those identified in cells) were common between EVs derived from cells and patients derived-exosomes. These miRs detected in circulating EVs could provide a specific and reliable signature in response to ionizing radiation, which could be useful for monitoring the effectiveness of radiotherapy. Further experiments on a larger patients population with clinical data could also help to define whether this signature might have a prognostic value on the response to radiotherapy.

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Section: Discussionsupporting

confidence: 61%

Radiotherapy induces specific miRNA expression profiles in glioblastoma exosomes

Boukredine

Saada

Durand

et al. 2021

Preprint

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“…Increased expression of miR-1949 was previously shown in injured kidney tissue in a rat model of deep hypothermic circulatory arrest [ 49 ]. Previous research demonstrated increased expression of miR-3084-3p in the renal cortices of mice treated with 177 Lu-octreotate, and this radionuclide therapy used for treating neuroendocrine tumors is known to cause renal toxicity at the level of the proximal tubule [ 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

Cadmium Nephrotoxicity Is Associated with Altered MicroRNA Expression in the Rat Renal Cortex

Fay

Alt

Ryba

et al. 2018

Toxics

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Cadmium (Cd) is a nephrotoxic environmental pollutant that causes a generalized dysfunction of the proximal tubule characterized by polyuria and proteinuria. Even though the effects of Cd on the kidney have been well-characterized, the molecular mechanisms underlying these effects have not been fully elucidated. MicroRNAs (miRNAs) are small non-coding RNAs that regulate cellular and physiologic function by modulating gene expression at the post-transcriptional level. The goal of the present study was to determine if Cd affects renal cortex miRNA expression in a well-established animal model of Cd-induced kidney injury. Male Sprague-Dawley rats were treated with subcutaneous injections of either isotonic saline or CdCl2 (0.6 mg/kg) 5 days a week for 12 weeks. The 12-week Cd-treatment protocol resulted in kidney injury as determined by the development of polyuria and proteinuria, and a significant increase in the urinary biomarkers Kim-1, β2 microglobulin and cystatin C. Total RNA was isolated from the renal cortex of the saline control and Cd treated animals, and differentially expressed miRNAs were identified using µParafloTM microRNA microarray analysis. The microarray results demonstrated that the expression of 44 miRNAs were significantly increased and 54 miRNAs were significantly decreased in the Cd treatment group versus the saline control (t-test, p ≤ 0.05, N = 6 per group). miR-21-5p, miR-34a-5p, miR-146b-5p, miR-149-3p, miR-224-5p, miR-451-5p, miR-1949, miR-3084a-3p, and miR-3084c-3p demonstrated more abundant expression and a significant two-fold or greater increased expression in the Cd-treatment group versus the saline control group. miR-193b-3p, miR-455-3p, and miR-342-3p demonstrated more abundant expression and a significant two-fold or greater decreased expression in the Cd-treatment group versus the saline control group. Real-time PCR validation demonstrated (1) a significant (t-test, p ≤ 0.05, N = 6 per group) increase in expression in the Cd-treated group for miR-21-5p (2.7-fold), miR-34a-5p (10.8-fold), miR-146b-5p (2-fold), miR-224-5p (10.2-fold), miR-3084a-3p (2.4-fold), and miR-3084c-3p (3.3-fold) and (2) a significant (t-test, p ≤ 0.05, N = 6 per group) 52% decrease in miR-455-3p expression in the Cd-treatment group. These findings demonstrate that Cd significantly alters the miRNA expression profile in the renal cortex and raises the possibility that dysregulated miRNA expression may play a role in the pathophysiology of Cd-induced kidney injury. In addition, these findings raise the possibility that Cd-dysregulated miRNAs might be used as urinary biomarkers of Cd exposure or Cd-induced kidney injury.

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“…miR107 is overexpressed in mouse renal cortical tissue after administration of 177 Lu-octreotate, which is a radiopharmaceutical used for treatment of neuroendocrine cancers. 103 However, a recent study found that long-term and excessive use of 900 MHz radiofrequency radiation downregulated rno-miR107 expression in Wistar albino adult male rat brains. 104 …”

Section: Factors Influencing Mir107 Expression In Cancer Cell Linesmentioning

confidence: 97%

Pleiotropic functions of miR107 in cancer networks

Luo¹,

Zheng²,

Zhang³

2018

OTT

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MicroRNAs are short regulatory RNAs that posttranscriptionally modulate gene expression and thus play crucial roles in controlling cancer-onset, growth, and progression processes. miR107, a highly conserved microRNA that maps to intron 5 of the PANK1 gene, contributes to the regulation of normal and tumor biological processes. Studies have reported that miR107 has oncogenic or tumor-suppressor functions in different human tumors. The pleiotropic functions of miR107 in various cancers are achieved via its targeting different genes that are involved in tumor proliferation, invasiveness, metastasis, angiogenesis, and chemotherapy-response pathways. The carcinogenicity or cancer-suppressor effects of miR107 occur in a tissue- and cell-specific manner, and the expression level of miR107 can be affected by various factors, including epigenetic and genetic factors, treatment exposure, and daily diet. A comprehensive analysis of the current literature suggests that miR107 functions as a central element in the regulation of cancer networks and can be used as a potential diagnostic and prognostic biomarker and drug target for therapeutic intervention.

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Distinct microRNA Expression Profiles in Mouse Renal Cortical Tissue after 177Lu-octreotate Administration

Cited by 7 publications

References 48 publications

Radiotherapy induces specific miRNA expression profiles in glioblastoma exosomes

Radiotherapy induces specific miRNA expression profiles in glioblastoma exosomes

Cadmium Nephrotoxicity Is Associated with Altered MicroRNA Expression in the Rat Renal Cortex

Pleiotropic functions of miR107 in cancer networks

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