MicroRNA-130a promotes the metastasis and epithelial-mesenchymal transition of osteosarcoma by targeting PTEN

Abstract

MicroRNAs, which serve as post-transcriptional modulators of numerous genes, have been found to be important regulators during the pathogenesis of osteosarcoma. This study demonstrates for the first time that microRNA-130a (miR-130a) is significantly upregulated in osteosarcoma, and associated with the metastasis of osteosarcoma. Elevated level of miR-130a was closely correlated with poor clinical features and prognosis of osteosarcoma patients. In vitro assays revealed that miR-130a could potentiate the migration, invasion and the epithelial-mesenchymal transtion (EMT) of osteosarcoma cells. Moreover, phosphatase and tensin homolog (PTEN) was confirmed as not only a direct downstream target but also a functional mediator of miR-130a. MiR-130a exerted promoting effects on metastatic behavior and EMT of osteosarcoma cells through suppressing PTEN expression. Based on these findings, we conclude that miR-130a is a promising prognostic biomarker for osteosarcoma patients, and targeting miR-130a may be a potential treatment option for osteosarcoma patients with metastasis.

Macrophage‐derived extracellular vesicles mediate smooth muscle hyperplasia: role of altered miRNA cargo in response to HIV infection and substance abuse

“…Recently, Brock et al , (76) reported a role of miR-130a in hypoxia-induced smooth muscle proliferation leading to pulmonary hypertension. Specifically, miR-130a is known to negatively regulate PTEN expression in various types of cancer (77) by directly binding to the 3′UTR of PTEN (37–40). Because we observed no significant change in the expression of endogenous precursor miR-130a level upon addition of H+C EVs over HPASMCs, our findings suggest transfer of mature miR-130a from EVs to HPASMCs that leads to inhibition of PTEN and therefore activation of PI3K/AKT-dependent smooth muscle proliferation.…”

“…The up-regulated miR-130a has been reported to directly target PTEN, a tumor-suppressor protein that negatively regulates phosphorylation and activation of AKT (37)(38)(39)(40). In addition, miR-130a is known to target tumor-suppressor complexes (TSCs)-1 and -2, a cell growth inhibitor negatively regulated by AKT (41).…”

Prognostic value of microRNAs in osteosarcoma: a meta-analysis

“…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].…”

“…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).…”

“…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).…”