Clinical significance of microRNA-130b in osteosarcoma and in cell growth and invasion

Yu, Liedao; Jin, Rilong; Gu, Pengcheng; Ling, Zhi-Heng; Lin, Xiang-Jin; Du, Jingyu

doi:10.1016/j.apjtm.2015.07.026

Cited by 11 publications

(13 citation statements)

References 29 publications

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“…High expressions of miRNA210, 17-92 cluster, 128, 9, 214, 542-5p, 130b, 130a, 199b-5p were associated with poor prognosis of osteosarcoma patients, [10, 12, 14, 19, 23, 26, 27, 29, 31]. Eight studies were included to analyze OS with miRNA210, 17-92 cluster, 128, 9, 214, 130b, 130a, 199-5p in 732 patients [10, 12, 19, 23, 26, 27, 29, 31].…”

Section: Resultsmentioning

confidence: 99%

“…Eight studies were included to analyze OS with miRNA210, 17-92 cluster, 128, 9, 214, 130b, 130a, 199-5p in 732 patients [10, 12, 19, 23, 26, 27, 29, 31]. The HR ranged between 0.33 and 0.67 with a pooled HR for deaths of 0.45 (0.35-0.60, p <0.00001) with low expression of miRNA, and the test for heterogeneity gave no significant results (χ 2 =2.47, p =0.93, I 2 =0%) (Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…The HR ranged between 0.33 and 0.67 with a pooled HR for deaths of 0.45 (0.35-0.60, p <0.00001) with low expression of miRNA, and the test for heterogeneity gave no significant results (χ 2 =2.47, p =0.93, I 2 =0%) (Table 2). The EFS was analyzed with miRNA210, 17-92 cluster, 128, 214, 542-5p, 130b, 130a, 199b-5p based on 8 studies including 693 patients [10, 12, 14, 19, 23, 26, 29, 31]. The pooled HR of high miRNA for adverse events was 0.46 with a range from 0.30 to 0.71 (0.35-0.60, p <0.00001), and the test for heterogeneity gave no significant results (χ 2 =4.37, p =0.74, I 2 =0%) (Table 2).…”

Section: Resultsmentioning

confidence: 99%

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Prognostic value of microRNAs in osteosarcoma: a meta-analysis

Kim¹,

Goh

Lee

et al. 2017

Oncotarget

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BACKGROUNDOsteosarcoma is the most common primary bone malignancy. We meta-analyzed the prognostic value of altered miRNAs in patients with osteosarcoma.METHODSSources from MEDLINE (from inception to August 2016) and EMBASE (from inception to August 2016) were searched. Studies of osteosarcoma with results of miRNA and studies that reported survival data were included and two authors performed the data extraction independently. Any discrepancies were resolved by a consensus. The outcome was overall survival and event-free survival assessed using hazard ratios (HRs).RESULTSAfter reviewing the full text of 65 articles, 25 studies including 2,278 patients were eligible in this study. The pooled HR for deaths was 1.40 (95% confidence interval [CI] 1.01-1.94, p=0.04) with random-effects model (χ2=113.08, p<0.00001, I2=79%) for patients of osteosarcoma with lower expression of miRNA. However, the pooled HR for events was not significant (HR 0.97, 0.63-1.48, p=0.87, χ2=72.65, p<0.00001, I2=79%). In pathway analysis of miRNAs, miRNA449a, 199-5p, 542-5p have common target genes.CONCLUSIONSExpression level of miRNA in patients of osteosarcoma is important as a prognostic factor.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Prognostic value of microRNAs in osteosarcoma: a meta-analysis

Kim¹,

Goh

Lee

et al. 2017

Oncotarget

View full text Add to dashboard Cite

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“…For example, miR-27a was found to overexpress in serum of OS patients, indicating its potential to be a diagnostic marker for OS (19). Another study found that the elevated miR-130b in OS tissues was related to the aggressive progression of OS patients, thus affecting the rate of survival (20). There were also downregulated miRNAs detected in OS tumor cells, such as miR-29b, miR-181b, miR-142-5p and miR-16 (21–23) which may play a significant role in osteosarcomagenesis.…”

Section: Discussionmentioning

confidence: 99%

miR-22 promotes apoptosis of osteosarcoma cells via inducing cell cycle arrest

et al. 2017

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To study the effects of miR-22 on the proliferation and the apoptosis of osteosarcoma MG-63 cell line and to explore the potential molecular mechanism that miR-22 regulates this biological process. Quantitive real-time polymerase chain reaction (RT-qPCR) was performed to explore the miRNA level of miR-22. The MG-63 cell line was infected with miR-22 mimics for establishment of miR-22 overexpression. Non-infected cells were in blank group and cells infected with empty vector were served as negative control (NC group). MTT assay was conducted to measure cell viability. The cell cycle and apoptosis were explored using flow cytometry and the apoptosis-related markers were detected by western blotting. RT-qPCR results revealed that the miR-22 miRNA level in the MG-63 cells was significantly lower than that in osteoblasts (P<0.05). MTT assay showed that the MG-63 cells infected with miR-22 mimics exhibited markedly decreased proliferation ability compared with blank and empty vector (NC) groups. Next, we found that overexpression of miR-22 remarkably increased the apoptosis of the MG-63 cells, evidenced from the flow cytometry results and elevated Bax and reduced Bcl-2. Furthermore, results revealed that percentage of the cells at G0/G1 phase in miR-22 mimic group (66.75±3.67%) was significantly higher than blank (52.9±2.58%) and NC (50.5±2.45%) groups. miR-22 attenuated the proliferation and induced the apoptosis of the MG-63 cells via promoting G0/G1 cell cycle arrest. Thus, miR-22 may have the potential to be a novel therapeutic in treatment of osteosarcoma.

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“…Furthermore, miR-130b was identified as oncogenic miR and is part of pan-cancer oncogenic superfamily that targets key pathways often deregulated in cancer including p53 and TGFβ 12 . The majority of miR-130b studies have been in epithelial based tumors; but several sarcomas, including leiomyosarcoma, osteosarcoma, and ES have shown enhanced expression of miR-130b 13–15 . Overexpression of miR-130b correlated with poor event free survival and overall survival in ES; however, its function and role in dictating sarcoma biology and metastasis is not understood 14 .…”

Section: Introductionmentioning

confidence: 99%

miR‐130b directly targets ARHGAP1 to drive activation of a metastatic CDC42‐PAK1‐AP1 positive feedback loop in Ewing sarcoma

Satterfield

Shuck

Kurenbekova

et al. 2017

Intl Journal of Cancer

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Ewing Sarcoma (ES) is a highly aggressive bone tumor with peak incidence in the adolescent population. It has a high propensity to metastasize, which is associated with dismal survival rates of approximately 25%. To further understand mechanisms of metastasis we investigated microRNA regulatory networks in ES. Our studies focused on miR-130b due to our analysis that enhanced expression of this microRNA has clinical relevance in multiple sarcomas, including ES. Our studies provide insights into a novel positive feedback network involving the direct regulation of miR-130b and activation of downstream signaling events contributing towards sarcoma metastasis. Specifically, we demonstrated miR-130b induces proliferation, invasion, and migration in vitro and increased metastatic potential in vivo. Using microarray analysis of ES cells with differential miR-130b expression we identified alterations in downstream signaling cascades including activation of the CDC42 pathway. We identified Arhgap1, which is a negative regulator of CDC42, as a novel, direct target of miR-130b. In turn, downstream activation of PAK1 activated the JNK and AP-1 cascades and downstream transcriptional targets including IL-8, MMP1 and CCND1. Furthermore, chromatin immunoprecipitation of endogenous AP-1 in ES cells demonstrated direct binding to an upstream consensus binding site within the miR-130b promoter. Finally, small molecule inhibition of PAK1 blocked miR-130b activation of JNK and downstream AP-1 target genes, including primary miR-130b transcripts, and mir-130b oncogenic properties, thus identifying PAK1 as a novel therapeutic target for ES. Taken together, our findings identify and characterize a novel, targetable miR-130b regulatory network that promotes ES metastasis.

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Clinical significance of microRNA-130b in osteosarcoma and in cell growth and invasion

Cited by 11 publications

References 29 publications

Prognostic value of microRNAs in osteosarcoma: a meta-analysis

Prognostic value of microRNAs in osteosarcoma: a meta-analysis

miR-22 promotes apoptosis of osteosarcoma cells via inducing cell cycle arrest

miR‐130b directly targets ARHGAP1 to drive activation of a metastatic CDC42‐PAK1‐AP1 positive feedback loop in Ewing sarcoma

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