MicroRNA-18a enhances the radiosensitivity of cervical cancer cells by promoting radiation-induced apoptosis

Li, Sha; Pan, Xia; Yang, Qin; Wen, Lu; Jiang, Yao; Zhao, Yingchao; Li, Guiling

doi:10.3892/or.2015.3929

Cited by 45 publications

(39 citation statements)

References 41 publications

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“…Several miRNAs appear to modulate and regulate these DNA repair mechanisms. For example, in cervical cancer cell lines, upregulation of miR-18a decreases the ATM level and attenuates efficient DSB repair after radiotherapy (46). Two further examples of interaction between miRNAs and the DSB repair machinery by ATM modulation are miR-101 and miR-421.…”

Section: Mirnas Modulating Dna Damage Responsementioning

confidence: 99%

MicroRNAs and Their Impact on Radiotherapy for Cancer

et al. 2016

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Section: Mirnas Modulating Dna Damage Responsementioning

confidence: 99%

MicroRNAs and Their Impact on Radiotherapy for Cancer

et al. 2016

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“…Previous studies indicate that miRNAs directly affect radioresistance by interfering with specific pathways [4], including sensing DNA damage [5], repair of DNA double-strand breaks (DSBs) [6], cell cycle checkpoint activation [7], formation of reactive oxygen species [8] and apoptosis [9], and autophagy [10]. miR-19b-3p belongs to both the miR-17-92 and miR-106-363 clusters, which play significant roles in proliferation and cell survival [11, 12].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-19b-3p regulates nasopharyngeal carcinoma radiosensitivity by targeting TNFAIP3/NF-κB axis

Huang

et al. 2016

J Exp Clin Cancer Res

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BackgroundNasopharyngeal carcinoma (NPC) is among the most common squamous cell carcinoma in South China and Southeast Asia. Radiotherapy is the primary treatment for NPC. However, radioresistance acts as a significant factor that limits the efficacy of radiotherapy for NPC patients. Growing evidence supports that microRNAs (miRNAs) play an important role in radiation response.MethodsReal-time quantitative PCR was used to analyze the expression of miR-19b-3p in NPC cell lines and NP69. miR-19b-3p expression profiles in NPC tissues were obtained from the Gene Expression Omnibus database. The effect of miR-19b-3p on radiosensitivity was evaluated by cell viability assays, colony formation assays and in vivo experiment. Apoptosis and cell cycle were examined by flow cytometry. Luciferase reporter assay was used to assess the target genes of miR-19b-3p. Expression of target proteins and downstream molecules were analyzed by Western blot.ResultsmiR-19b-3p was upregulated in NPC and served as an independent predictor for reduced patient survival. Radioresponse assays showed that miR-19b-3p overexpression resulted in decreased sensitivity to irradiation, whereas miR-19b-3p downregulation resulted in increased sensitivity to irradiation in vitro. Moreover, miR-19b-3p decreased the sensitivity of NPC cells to irradiation in vivo. Luciferase reporter assay confirmed that TNFAIP3 was a direct target gene of miR-19b-3p. Knockdown of TNFAIP3 reduced sensitivity to irradiation, whereas upregulation of TNFAIP3 expression reversed the inhibitory effects of miR-19b-3p on NPC cell radiosensitivity. Mechanistically, we found that miR-19b-3p increased NPC cell radioresistance by activating the TNFAIP3/ NF-κB axis.ConclusionsmiR-19b-3p contributes to the radioresistance of NPC by activating the TNFAIP3/ NF-κB axis. miR-19b-3p is a determinant of NPC radioresponse and may serve as a potential therapeutic target in NPC treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0465-1) contains supplementary material, which is available to authorized users.

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“…For example, miR‐18a‐5p enhanced radiosensitivity via downregulating ATM in cervical cancer,52 colorectal cancer,53 and breast cancer 54. It was addressed that miR‐18 targeted heat shock transcription factor 2 (HSF2),55 while HSF2 upregulated HIF‐1α 56.…”

Section: Discussionmentioning

confidence: 99%

Radiosensitizing effects of miR‐18a‐5p on lung cancer stem‐like cells via downregulating both ATM and HIF‐1α

Chen

et al. 2018

Cancer Medicine

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Lung cancer is one of the main causes of cancer mortality globally. Most patients received radiotherapy during the course of disease. However, radioresistance generally occurs in the majority of these patients, leading to poor curative effect, and the underlying mechanism remains unclear. In the present study, miR‐18a‐5p expression was downregulated in irradiated lung cancer cells. Overexpression of miR‐18a‐5p increased the radiosensitivity of lung cancer cells and inhibited the growth of A549 xenografts after radiation exposure. Dual luciferase report system and miR‐18a‐5p overexpression identified ataxia telangiectasia mutated (ATM) and hypoxia inducible factor 1 alpha (HIF‐1α) as the targets of miR‐18a‐5p. The mRNA and protein expressions of ATM and HIF‐1α were dramatically downregulated by miR‐18a‐5p in vitro and in vivo. Clinically, plasma miR‐18a‐5p expression was significantly higher in radiosensitive than in radioresistant group (P < .001). The cutoff value of miR‐18a‐5p >2.28 was obtained from receiver operating characteristic (ROC) curve. The objective response rate (ORR) was significantly higher in miR‐18a‐5p‐high group than in miR‐18a‐5p‐low group (P < .001). A tendency demonstrated that the median local progression‐free survival (PFS) from radiotherapy was longer in miR‐18a‐5p‐high than in miR‐18a‐5p‐low group (P = .082). The median overall survival (OS) from radiotherapy was numerically longer in miR‐18a‐5p‐high than in miR‐18a‐5p‐low group (P = .281). The sensitivity and specificity of plasma miR‐18a‐5p to predict radiosensitivity was 87% and 95%, respectively. Collectively, these results indicate that miR‐18a‐5p increases the radiosensitivity in lung cancer cells and CD133+ stem‐like cells via downregulating ATM and HIF‐1α expressions. Plasma miR‐18a‐5p would be an available indicator of radiosensitivity in lung cancer patients.

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MicroRNA-18a enhances the radiosensitivity of cervical cancer cells by promoting radiation-induced apoptosis

Cited by 45 publications

References 41 publications

MicroRNAs and Their Impact on Radiotherapy for Cancer

MicroRNAs and Their Impact on Radiotherapy for Cancer

MicroRNA-19b-3p regulates nasopharyngeal carcinoma radiosensitivity by targeting TNFAIP3/NF-κB axis

Radiosensitizing effects of miR‐18a‐5p on lung cancer stem‐like cells via downregulating both ATM and HIF‐1α

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