miR-17 inhibitor suppressed osteosarcoma tumor growth and metastasis via increasing PTEN expression

Gao, Yong; Luo, Lan; Li, Shuai; Yang, Cao

doi:10.1016/j.bbrc.2014.01.061

Cited by 59 publications

(47 citation statements)

References 20 publications

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“…The relevance of this pathway in cancer has been highlighted by the elevated number of components within the cascades, such as the activation of AKT kinases, which play crucial roles in cell survival, cell proliferation, angiogenesis, and anabolic metabolism, and represent one of the main targets for cancer therapy 26. In osteosarcomas, Gao et al27 and Shen et al16 both observed the downregulation of PTEN expression in osteosarcoma tissues and cell lines, which was in line with our findings. In these previous studies, PTEN functions as a direct target for miR-17 and miR-128, respectively.…”

Section: Discussionsupporting

confidence: 89%

Upregulation of micro-ribonucleic acid-128 cooperating with downregulation of PTEN confers metastatic potential and unfavorable prognosis in patients with primary osteosarcoma

Tian¹,

Guo²,

Yu³

et al. 2014

OTT

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ObjectiveAbnormal expression of micro-ribonucleic acid (miRNA [miR])-128 has been observed in various human cancer types, and its validated target genes are implicated in cancer-related cellular processes, such as cell proliferation, differentiation, and apoptosis. Especially, it has been demonstrated that miR-128 may play an important role in the proliferation of human osteosarcoma cells in vitro by directly inhibiting PTEN, which functions as a tumor suppressor in this malignancy. In the current study, we investigated the involvement of miR-128 and its target gene PTEN in tumor progression and prognosis in patients with primary osteosarcoma.Materials and methodsExpression levels of miR-128 and PTEN messenger RNA in osteosarcoma and noncancerous bone tissues obtained from 100 patients with primary osteosarcoma were detected by quantitative real-time polymerase chain reaction.ResultsExpression levels of miR-128 and PTEN messenger RNA in osteosarcoma tissues were significantly higher and lower, respectively, than those in noncancerous bone tissues (both P<0.001). In addition, high miR-128 expression and low PTEN expression, alone (miR-128-high or PTEN-low) or combined (miR-128-high/PTEN-low), were all dramatically associated with poor response to chemotherapy and positive metastasis. More importantly, the associations of miR-128-high/PTEN-low expression with these clinicopathological parameters were more significant than miR-128-high or PTEN-low alone. Finally, miR-128 expression, PTEN expression, miR-128/PTEN expression, the response to chemotherapy and the metastatic status were all identified as independent prognostic factors for overall survival and disease-free survival.ConclusionThese findings indicate for the first time that the deregulation of miR-128 and its target gene PTEN may be involved in the aggressive progression of human osteosarcoma. Notably, the upregulation of miR-128 cooperating with the downregulation of PTEN may confer an unfavorable prognosis in patients with this malignancy.

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Section: Discussionsupporting

confidence: 89%

Upregulation of micro-ribonucleic acid-128 cooperating with downregulation of PTEN confers metastatic potential and unfavorable prognosis in patients with primary osteosarcoma

Tian¹,

Guo²,

Yu³

et al. 2014

OTT

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“…Introduction of miR-143 in OS cell lines halts cell metastasis, but has no effects on cell proliferation [7]. More microRNAs involved in OS metastasis have been reported, such as miR-27a [14], miR-17 [15], and miR-34a [16], but excluding miR-26b. The roles of miR-26b have been investigated in several cancers.…”

Section: Introductionmentioning

confidence: 97%

MicroRNA-26b inhibits metastasis of osteosarcoma via targeting CTGF and Smad1

et al. 2015

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Downregulation of miR-26b has been found in various cancers, but it has never been investigated in osteosarcoma. In this study, we demonstrated downregulation of miR-26b in osteosarcoma tissues, negatively correlated with the expression of connective tissue growth factor (CTGF) and Smad1. Luciferase reporter assay confirmed the interaction of miR-26b with the 3' untranslated regions (UTRs) of CTGF and Smad1. Transfection of miR-26b in osteosarcoma cells suppressed the expression of CTGF and Smad1, suggesting CTGF and Smad1 as direct targets of miR-26b. Overexpression of miR-26b inhibited the migration of osteosarcoma cells, which was reversed by overexpression of CTGF or Smad1. Knockdown of CTGF by small interfering RNA (siRNA) interference blocked the activation of Smad1, ERK1/2, and MMP2, which was opposite to the overexpression of CTGF. Differently, Smad1 did not significantly affect CTGF level, but mediated ERK1/2 phosphorylation and MMP2 activation. Furthermore, miR-26b inhibited lung metastasis of osteosarcoma in vivo. Our data indicated that downregulation of miR-26b in osteosarcoma elevated the levels of CTGF and Smad1, facilitating osteosarcoma metastasis.

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“…Recent evidence has demonstrated that miRNAs play critical roles in many biological processes, such as lineage determination and cell proliferation, migration, apoptosis and differentiation 2, 17, 18, 19. Deregulation of miRNAs is involved in the initiation, progression and metastasis of various types of cancer, in which miRNAs can act as oncogenesor tumour suppressors 20, 21, 22, 23.…”

Section: Introductionmentioning

confidence: 99%

Retracted: MicroRNA‑224 promotes the sensitivity of osteosarcoma cells to cisplatin by targeting Rac1

Geng

Fang

et al. 2016

J Cellular Molecular Medi

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Osteosarcoma is the most common primary bone tumour in children and adolescents. Accumulating evidence has shown that microRNAs (miRNAs) participate in the development of almost all types of cancer. Here, we investigated the role of miR‐224 in the development and progression of osteosarcoma. We demonstrated that miR‐224 was down‐regulated in osteosarcoma cell lines and tissues. Lower miR‐224 levels were correlated with shorter survivalin osteosarcoma patients. Furthermore, overexpression of miR‐224 suppressed osteosarcoma cell proliferation, migration and invasion and contributed to the increased sensitivity of MG‐63 cells to cisplatin. We identified Rac1 as a direct target gene of miR‐224 in osteosarcoma. Rac1 expression was up‐regulated in the osteosarcoma cell lines and tissues, and there was an inverse correlation between Rac1 and miR‐224 expression in osteosarcoma tissues. Furthermore, rescuing Rac1 expression decreased the sensitivity of miR‐224‐overexpressing MG‐63 cells to cisplatin. We also demonstrated that ectopic expression of Rac1 promoted the proliferation, migration and invasion of miR‐224‐overexpressing MG‐63 cells. These data suggest that miR‐224 plays a tumour suppressor role in the development of osteosarcoma and is related to the sensitivity of osteosarcoma to cisplatin.

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miR-17 inhibitor suppressed osteosarcoma tumor growth and metastasis via increasing PTEN expression

Cited by 59 publications

References 20 publications

Upregulation of micro-ribonucleic acid-128 cooperating with downregulation of PTEN confers metastatic potential and unfavorable prognosis in patients with primary osteosarcoma

Upregulation of micro-ribonucleic acid-128 cooperating with downregulation of PTEN confers metastatic potential and unfavorable prognosis in patients with primary osteosarcoma

MicroRNA-26b inhibits metastasis of osteosarcoma via targeting CTGF and Smad1

Retracted: MicroRNA‑224 promotes the sensitivity of osteosarcoma cells to cisplatin by targeting Rac1

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