Radiosensitive gene therapy through imRNA expression for silencing manganese superoxide dismutase

Qu, Yaming; Zhao, Suping; Hong, Jinsheng; Tang, Siyuan

doi:10.1007/s00432-009-0739-5

Cited by 17 publications

(18 citation statements)

References 28 publications

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“…The KLK10 mRNA expression levels showed only slight decrease after miRNA transfection ( Figure 7B). Decreased mRNA expression after miRNA transfection has been reported earlier (Lim et al, 2005;Yu et al, 2005;Nishi et al, 2009;Pan et al, 2009;Qu et al, 2009;Arora et al, 2010), and may be due to partial degradation of the KLK10 transcript or other indirect effects. Figure 4 Effect of transfection of miR-224 and miR-516a on luciferase activity as measured with the pMIR -KLK10.…”

Section: Mirna Target Validation: Effect Of Mirnas On Klk10mentioning

confidence: 66%

Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer

et al. 2010

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BACKGROUND: Kallikrein-related peptidases (KLKs) are a family of serine proteases that have been shown to be dysregulated in several malignancies including ovarian cancer. The control of kallikrein genes and their physiological function in cancer is not well understood. We hypothesized that microRNAs (miRNAs) represent a novel mechanism for post-transcriptional control of KLK expression in cancer. METHODS: We first analysed miRNA expression in ovarian cancer in silico. A total of 98 miRNAs were reported to have altered expression in ovarian cancer. Three of these miRNAs were predicted to target KLK10. We experimentally verified the predicted miR -KLK10 interaction using two independent techniques, a luciferase assay with a construct containing the KLK10 3 0 untranslated region (UTR), pMIR -KLK10, and measuring KLK10 protein levels after transfection with miRNA. RESULTS: When we co-transfected cells with pMIR -KLK10 and either let-7f, miR-224, or mR-516a, we saw decreased luciferase signal, suggesting that these miRNAs can target KLK10. We then examined the effect of these three miRNAs on KLK10 protein expression and cell growth. Transfection of all miRNAs, let-7f, miR-224, and miR-516a led to a decrease in protein expression and cellular growth. This effect was shown to be dose dependent. The KLK10 protein levels were partially restored by co-transfecting let-7f and its inhibitor. In addition, there was a slight decrease in KLK10 mRNA expression after transfection with let-7f. CONCLUSIONS: Our results confirm that KLKs can be targeted by more than one miRNA. Increased expression of certain miRNAs in ovarian cancer can lead to decreased KLK protein expression and subsequently have a negative effect on cell proliferation. This dose-dependent effect suggests that a 'tweaking' or 'fine-tuning' mechanism exists in which the expression of one KLK can be controlled by multiple miRNAs. These data together suggest that miRNA may be used as potential therapeutic options and further studies are required.

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Section: Mirna Target Validation: Effect Of Mirnas On Klk10mentioning

confidence: 66%

Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer

et al. 2010

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“…In contrast, cells have a multilayered interdependent antioxidant system to safeguard against the toxicity of the ROS, such as glutathione and superoxide dismutase, which can react chemically with ROS to eliminate their damaging effects and defense against oxidative stress [34,35]. It has been proved that member of MRP family could protect cells from the toxic effects by exporting the xenobiotics combined a e is the bottom of the natural logarithm, D is the absorbed dose, D0 is the mean lethal dose, N is the extrapolate number, Dq is the standard threshold dose, SER (sensitization enhancement ratio) is the ratio of D0, SER > 1 indicates radiosensitization.…”

Section: Discussionmentioning

confidence: 95%

“…4A). Meanwhile, cell apoptosis analyzed by Hoechst 33342 staining showed the cell apoptotic rates were significantly increased in SW480-KD 61 34. (±2.95) % and HT29-KD 58.47 (±3.61) %, as compared with those of SW480-NC 40.25 (±3.19) %, HT29-NC 38.76 (±2.54) % and SW480-CON 41.63 (±2.98) %, HT29-CON 39.67 (±2.41) % (p < 0.05, respectively)…”

mentioning

confidence: 99%

Multidrug resistance-associated protein 3 confers resistance to chemoradiotherapy for rectal cancer by regulating reactive oxygen species and caspase-3-dependent apoptotic pathway

Zhang

Wang

et al. 2014

Cancer Letters

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“…It has been reported that lentiviral vectors have been applied successfully to deliver miRs for gene therapy of NPC. Silencing the radioresistance manganese superoxide dismutase (SOD2) by miR-155 could reduce NPC resistance to IR 37 , and lenti-miR-26a inhibited the tumorigenicity of NPC cells in nude mice 26 . These studies indicate the potential application of miRs in increasing NPC sensitivity to radiotherapy and inhibiting NPC development.…”

Section: Discussionmentioning

confidence: 99%

Hsa-miR-24-3p increases nasopharyngeal carcinoma radiosensitivity by targeting both the 3′UTR and 5′UTR of Jab1/CSN5

et al. 2016

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Radiotherapy is the standard therapy for nasopharyngeal carcinoma (NPC); however, radioresistance can hinder successful treatment. Here, we report that miR-24 acts as a tumor suppressor and radiosensitizer in NPC cells and xenografts by targeting Jab1/CSN5. Although accumulating evidence has shown that Jab1/CSN5 functions as an oncoprotein in human cancers, its regulation through miRs has not been described. In this study, we found that Jab1/CSN5 functioned in a manner opposite that of miR-24 in NPC tumorigenesis and radioresistance. We demonstrated that miR-24 inhibits Jab1/CSN5 translation via direct binding to its 3’UTR and 5’UTR, leading to tumor growth inhibition, and sensitizes NPC tumors to radiation in vivo. Furthermore, silencing Jab1/CSN5 phenocopied the function of miR-24 in NPC cells after ionizing radiation treatment, resulting in increased apoptosis. Finally, we analyzed 50 paired samples of primary and matched recurrent NPC tissues from 25 NPC patients and subjected them to high-throughput genomic quantitative nuclease protection assay for quantifying simultaneously miR and mRNA levels. Our results showed that miR-24 levels were significantly decreased in recurrent NPC and that levels of Jab1/CSN5, as its target, were higher than those in primary NPC. Together, our findings indicate that miR-24 inhibits NPC tumor growth and increases NPC radiosensitivity by directly regulating Jab1/CSN5 and that both miR-24 and Jab1/CSN5 can serve as prognostic markers for NPC recurrence; this, in turn, may provide a promising therapeutic strategy for reversing NPC radioresistance.

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Radiosensitive gene therapy through imRNA expression for silencing manganese superoxide dismutase

Abstract: The results presented suggest that miRNA for silencing SOD2 radiosensitizing gene therapy maybe applicable to the nasopharyngeal carcinoma, improving the therapeutic ratio of cancer radiotherapy.

Cited by 17 publications

References 28 publications

Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer

Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer

Multidrug resistance-associated protein 3 confers resistance to chemoradiotherapy for rectal cancer by regulating reactive oxygen species and caspase-3-dependent apoptotic pathway

Hsa-miR-24-3p increases nasopharyngeal carcinoma radiosensitivity by targeting both the 3′UTR and 5′UTR of Jab1/CSN5

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