MicroRNA-199a-5p promotes tumour growth by dual-targeting PIAS3 and p27 in human osteosarcoma

Wang, Chen; Ba, Ximing; Guo, Yu; Sun, Da; Jiang, Haoyang; Li, Wentao; Huang, Zhen; Zhou, Guangxin; Wu, Sujia; Zhang, Junfeng; Chen, Jiangning

doi:10.1038/srep41456

Cited by 39 publications

(42 citation statements)

References 47 publications

(52 reference statements)

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“…Extensive investigations of the role of miR‐199a‐5p in colorectal cancer showed that the overexpression of miR‐199a‐5p inhibited cell proliferation, migration, invasion, and induced cell apoptosis via targeting the expression of Rho‐associated coiled coil‐containing protein kinase 1 . In osteosarcoma, miR‐199a‐5p was found upregulated in tumor tissues and its downregulation led to cell proliferation and tumor growth inhibition . By introduction the miR‐199a‐5p inhibitor in an osteosarcoma xenograft model, the tumor volume and weight were significantly decreased, indicating the potential to use miR‐199a‐5p as a therapeutic target .…”

Section: Introductionmentioning

confidence: 99%

microRNA‐199a‐5p suppresses glioma progression by inhibiting MAGT1

Wang

et al. 2019

J of Cellular Biochemistry

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microRNAs (miRNAs) can function as a tumor suppressor or oncogenic genes in human cancers. Alternation expression of miR‐199a‐5p has been revealed in several human cancers. However, its expression pattern and biological roles in glioma remain unclear. Expression levels of miR‐199a‐5p in glioma were evaluated at first. The effects of miR‐199a‐5p expression on cell proliferation, migration, and invasion were investigated using the MTT assay, wound‐healing assay, and transwell invasion assay. The expression of miR‐199a‐5p was found to be reduced in glioma cell lines. Overexpression of miR‐199a‐5p inhibits glioma cell proliferation, migration, and invasion in vitro. Furthermore, the target of miR‐199a‐5p was predicted by TargetScan and validated by luciferase activity reporter assay. We found magnesium transporter 1 (MAGT1) was a direct target of miR‐199a‐5p. Overexpression of MAGT1 reversed the effects of miR‐199a‐5p on glioma cell behaviors. Taken together, our study revealed that miR‐199a‐5p and MAGT1 have the potential to be used as a biomarker for glioma.

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Section: Introductionmentioning

confidence: 99%

microRNA‐199a‐5p suppresses glioma progression by inhibiting MAGT1

Wang

et al. 2019

J of Cellular Biochemistry

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“…The miR-199a-5p directly binds to the 3′UTRs of the mRNA of both PIAS3 and p27 Kip1 and mediates the reduction of PIAS3 and p27 Kip1 proteins. The miR-199a-5p stimulates the STAT3, cell cycle progression, and tumor growth in osteosarcoma cells 36 . The miR-199a-5p promotes migration and tube formation of human cytomegalovirus-infected endothelial cells through downregulation of SIRT1 and eNOS 37 .…”

Section: Discussionmentioning

confidence: 99%

ROR2 suppresses metastasis of prostate cancer via regulation of miR-199a-5p–PIAS3–AKT2 signaling axis

et al. 2020

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Bones are the most common metastatic sites for prostate cancer (PCa). Receptor tyrosine kinase-like orphan receptor 2 (ROR2), a noncanonical Wnt receptor, plays crucial roles in skeletal morphogenesis, osteoblast differentiation, and bone formation. The role of ROR2 in PCa metastasis is unclear. We analyzed online datasets from Oncomine as well as using IHC staining on tissue array to determine the relationship between ROR2 expression level and disease outcome of PCa. To investigate how ROR2 regulates migration and invasion of PCa cells, we performed transwell assay and orthotopic xenograft model in nude mice. We then applied the Micro-Western Array (MWA), a high-throughput western blotting platform to analyze the downstream signaling pathways being regulated by ROR2. Compared with nonmalignant PZ-HPV-7 and RWPE-1 cells, PCa cell lines express lower level of ROR2 protein. Constitutive expression of ROR2 in PC-3, DU-145, or C4-2B PCa cells significantly suppressed the cell migration, invasion, and epithelial-mesenchymal transition (EMT) proteins. MWA, western blotting, and microRNA analysis showed that elevation of ROR2 suppressed the expression of miR-199a-5p, which in turn increased the expression of PIAS3. The upregulation of PIAS3 then decreased AKT2 and the phosphorylation of AKT, resulting in the inhibition of migration and invasion of PCa cells both in vitro and in orthotopic xenograft mice model. IHC staining of tissue array and Oncomine datasets analysis indicated that the gene and protein level of ROR2 is much lower in metastatic prostate tumors as compared with primary tumors or adjacent normal prostate tissues. Low level of ROR2 correlated to poor survival and high recurrent frequency in PCa patients. In conclusion, we discovered that ROR2 suppresses PCa metastasis via regulation of PIAS3-PI3K-AKT2 signaling axis.

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“…Previous studies have indicated that miRNAs function as oncogenes or tumor suppressors to regulate the expression of cancer-associated genes ( 10 , 11 ). Certain miRNAs have been demonstrated to be involved in OS progression: miRNA-503 suppresses cell proliferation and invasion in OS via targeting insulin-like growth factor 1 receptor ( 12 ); miR-187 inhibits tumor growth and invasion by directly targeting mitogen activated protein kinase 12 in OS ( 13 ); miRNA-199a-5p promotes tumor growth by dually targeting protein inhibitor of activated signal transducer and activator of transcription 3 and cyclin-dependent kinase inhibitor 1B in human OS ( 14 ). In a previous study, performed by Yin et al ( 9 ), miR-491 was identified to be downregulated in OS and to serve as a tumor suppressor, revealing that the upregulation of miRNA-491-5p suppressed proliferation and promoted apoptosis by targeting FOXP4 in human OS.…”

Section: Discussionmentioning

confidence: 99%

miR‑491‑5p inhibits osteosarcoma cell proliferation by targeting PKM2

Chen

Cao

et al. 2018

Oncol Lett

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Increasing evidence has indicated that microRNAs (miRNAs/miRs) are associated with tumorigenesis and the development of numerous cancer types. Previous studies have suggested miRNA-491-5p is downregulated in osteosarcoma (OS) and functions as a tumor suppressor. However, the biological roles and underlying mechanisms associated with miR-491-5p function in OS require further exploration. In the present study, it was demonstrated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) that miR-491-5p was downregulated in 36 pairs of OS tissues, compared with in adjacent normal bone tissues. Furthermore, CCK-8 and colony formation assays indicated that miR-491-5p mimics suppressed OS cell proliferation. However, an miR-491-5p inhibitor enhanced cell proliferation. In addition, luciferase reporter assays, RT-qPCR and western blot analysis demonstrated that PKM2 was a direct target of miR-491-5p. The miR-491-5p mimic inhibited the mRNA and protein expression of PKM2, while the miR-491-5p inhibitor promoted PKM2 mRNA and protein expression. In addition, PKM2 overexpression reversed the proliferation-inhibiting effects of miR-491-5p in OS cells. Therefore, these results indicated that miR-491-5p serves as a tumor suppressor in OS cells, which may be important in OS treatment.

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MicroRNA-199a-5p promotes tumour growth by dual-targeting PIAS3 and p27 in human osteosarcoma

Cited by 39 publications

References 47 publications

microRNA‐199a‐5p suppresses glioma progression by inhibiting MAGT1

microRNA‐199a‐5p suppresses glioma progression by inhibiting MAGT1

ROR2 suppresses metastasis of prostate cancer via regulation of miR-199a-5p–PIAS3–AKT2 signaling axis

miR‑491‑5p inhibits osteosarcoma cell proliferation by targeting PKM2

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