miR-513a-5p regulates radiosensitivity of osteosarcoma by targeting human apurinic/apyrimidinic endonuclease

Dai, Nan; Qu, Yi; Cun, Yanping; Zhong, Zhaoyang; Li, Chongyi; Shiheng, Zhang; Shan, Jinlu; Yang, Xia; Dai, Xiaoyan; Cheng, Yi; Xiao, He; Xu, Cheng-Xiong; Li, Mengxia; Wang, Dong

doi:10.18632/oncotarget.11003

Cited by 37 publications

(25 citation statements)

References 29 publications

(28 reference statements)

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“…Radiotherapy has been utilized for malignant tumor for decades. Radiotherapy is applied to a small proportion of OS patients such as inoperable OS and painful bone metastasis [ 5 ]. Local control could be achieved by radiotherapy which is used as an adjuvant method in OS patients receiving intralesional resection [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Activation of Sonic Hedgehog Signaling Is Associated with Human Osteosarcoma Cells Radioresistance Characterized by Increased Proliferation, Migration, and Invasion

Qü

Wang

et al. 2018

Med Sci Monit

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BackgroundRadioresistance restricts the application of radiotherapy in human osteosarcoma (OS). This study investigated the molecular mechanism of radioresistance in OS, which may provide clues to finding ideal targets for genetic therapy.Materila/MethodsThe human OS cell line MG63 was employed as parent cells. After repeat low-dose X-ray irradiation of MG63, the radioresistant OS cell line MG63R was produced. Colony formation assay was used to assess the radioresistance. Cell viability was evaluated by CCK-8 assay. Flow cytometry was used to detect cell apoptosis, and wound healing assay was used to evaluate invasive capacity. The nuclear translocation was evaluated by fluorescent immunohistochemistry. Protein expression levels were assessed by Western blotting. Specific siRNA against Shh was used to silence Shh.ResultsMore survival colony formation, elevated cell viability, less cell apoptosis, and increased wound closure were found in MG63R than in MG63 cells exposed to irradiation. The nuclear translocation of Gli, expression levels of Shh, Smo, Ptch1, Bcl2, active MMP2, and active MMP9 were increased in MG63R cells compared with MG63 cells. Transfection of Shh-siRNA suppressed expression levels of Shh, Smo, Ptch1, Bcl2, active MMP2, and active MMP9, as well as the nuclear translocation of Gli in MG63R cells. The cell viability, survival colony formation, and wound closure were impaired, whereas cell apoptosis was increased, in siRNA-transfected MG63R cells than in control MG63R cells exposed to irradiation.ConclusionsActivation of Shh signaling was involved in radioresistance of OS cells. Blocking this signaling can impair the radioresistance capacity of OS cells.

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Section: Introductionmentioning

confidence: 99%

Activation of Sonic Hedgehog Signaling Is Associated with Human Osteosarcoma Cells Radioresistance Characterized by Increased Proliferation, Migration, and Invasion

Qü

Wang

et al. 2018

Med Sci Monit

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“…For the brown module, which was mainly involved in DNA replication and mitotic nuclear division and was observed to be positively correlated with the trait of osteosarcoma tissue, previous studies have revealed that genes involved with DNA replication and DNA damage were associated with radiosensitivity of osteosarcoma [13], as well as drug sensitivity [14]. Our results indicated that genes in the brown module might be related with carcinogenesis of osteosarcoma and might provide insights for exploring drug targets for the treatment of osteosarcoma.…”

Section: Discussionmentioning

confidence: 99%

Identification of co-expression modules and pathways correlated with osteosarcoma and its metastasis

Wang

Zhong

et al. 2019

World J Surg Onc

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Background Osteosarcoma is the most common bone tumor that occurs in children. Methods To identify co-expression modules and pathways correlated with osteosarcoma and its clinical characteristics, we performed weighted gene co-expression network analysis (WGCNA) on RNA-seq data of osteosarcoma with 52 samples. Then we performed pathway enrichment analysis on genes from significant modules. Results A total of 5471 genes were included in WGCNA, and 16 modules were identified. Module-trait analysis identified that a module involved in microtubule bundle formation, drug metabolism-cytochrome P450, and IL-17 signaling pathway was negatively correlated with osteosarcoma and positively correlated with metastasis; a module involved in DNA replication was positively correlated with osteosarcoma; a module involved in cell junction was positively correlated with metastasis; and a module involved in heparin binding negatively correlated with osteosarcoma. Moreover, expression levels in four of the top ten differentially expressed genes were validated in another independent dataset. Conclusions Our analysis might provide insight for molecular mechanisms of osteosarcoma. Electronic supplementary material The online version of this article (10.1186/s12957-019-1587-7) contains supplementary material, which is available to authorized users.

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“…In support of this, decreasing Ape1 expression levels with small interfering RNA (siRNA) was able to sensitize osteosarcoma xenografts to the antiangiogenic endostatin [370]. The miRNA miR-513a-5p has been found to supress APE1 expression in osteosarcoma cell lines including HOS and U2-OS, rendering them radiosensitive [371]. In addition, miR-765 was found to sensitize osteosarcoma cells lines (HOS and 9901) and tumour xenografts to cisplatin due to downregulation of Ape1 [372], making targeting APE1 through miRNA a treatment option for resistant osteosarcoma.…”

Section: Alterations In Dna Repair Pathwaysmentioning

confidence: 91%

Targeting Molecular Mechanisms Underlying Treatment Efficacy and Resistance in Osteosarcoma: A Review of Current and Future Strategies

Lilienthal

Herold

2020

IJMS

192

140

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Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. Due to micrometastatic spread, radical surgery alone rarely results in cure. Introduction of combination chemotherapy in the 1970s, however, dramatically increased overall survival rates from 20% to approximately 70%. Unfortunately, large clinical trials aiming to intensify treatment in the past decades have failed to achieve higher cure rates. In this review, we revisit how the heterogenous nature of osteosarcoma as well as acquired and intrinsic resistance to chemotherapy can account for stagnation in therapy improvement. We summarise current osteosarcoma treatment strategies focusing on molecular determinants of treatment susceptibility and resistance. Understanding therapy susceptibility and resistance provides a basis for rational therapy betterment for both identifying patients that might be cured with less toxic interventions and targeting resistance mechanisms to sensitise resistant osteosarcoma to conventional therapies.

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miR-513a-5p regulates radiosensitivity of osteosarcoma by targeting human apurinic/apyrimidinic endonuclease

Cited by 37 publications

References 29 publications

Activation of Sonic Hedgehog Signaling Is Associated with Human Osteosarcoma Cells Radioresistance Characterized by Increased Proliferation, Migration, and Invasion

Activation of Sonic Hedgehog Signaling Is Associated with Human Osteosarcoma Cells Radioresistance Characterized by Increased Proliferation, Migration, and Invasion

Identification of co-expression modules and pathways correlated with osteosarcoma and its metastasis

Targeting Molecular Mechanisms Underlying Treatment Efficacy and Resistance in Osteosarcoma: A Review of Current and Future Strategies

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