Decreased expression of tumor suppressive miR-874 and its clinical significance in human osteosarcoma

Zhang, L Q; Sun, Shengjie; Li, W Y; Zuo, Feng; Xu, Xiao-Chao; Zhuang, Q.; Fang, Jun

doi:10.4238/2015.december.23.19

Cited by 14 publications

(11 citation statements)

References 21 publications

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“…Recently, several reports show that miRNA-874 (miR-874) expression is downregulated and functions as a tumor suppressor in several cancers, including non-small cell lung cancer (NSCLC) [ 9 ], breast cancer [ 10 ], osteosarcoma [ 11 , 12 ], gastric cancer [ 13 , 14 ], colorectal cancer [ 15 ], testis cancer [ 16 ], and maxillary sinus squamous cell carcinoma [ 17 ]. Moreover, miR-874 is significantly downregulated in breast cancer cells and its overexpression could suppress growth, colony formation and cycle of breast cancer cells and increase cell apoptosis [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

DNA methylation mediated silencing of microRNA-874 is a promising diagnosis and prognostic marker in breast cancer

et al. 2017

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MicroRNA-874 (miR-874) is downregulated in several human cancers and has been suggested to be a tumor suppressor gene. However, the molecular mechanism of miR-874 downregulation in breast cancer has not been well elucidated. Here we aimed to study the aberrant hyper-methylation of CpG sites with the utility of miR-874 downreregulation in breast cancer and evaluate the clinical function of miR-874 as a prognostic marker. The miR-874 expressions in cells and tissues of two breast cancer lines were measured by real-time PCR. The DNA methylation status of the miR-874 promoter region in 19 pairs of breast cancer and adjacent normal samples was analyzed with Sequenom EpiTYPER MassArray. To evaluate whether miR-874 is a potential prognostic marker in breast cancer, we also explored the clinical long-time follow-up records from The Cancer Genome Atlas (TCGA). We found miR-874 expression was downregulated in 47 pairs of breast cancer tissues. Moreover, univariate and multivariate analysis revealed miR-874 expression may be a prognostic biomarker of overall survival in breast cancer patients. Preconditioning with 5-Aza-CdR in two cell lines elevated miR-874 expressions. The data from Sequenom EpiTYPER MassArray showed that DNA methylation of the promoter region of miR-874 was upregulated and accompanied by decreased miR-874 expression, which was further confirmed by TCGA. After comprehensive considerations, we think miR-874, which might be served as a prognostic biomarker, is mediated by DNA methylation.

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Section: Introductionmentioning

confidence: 99%

DNA methylation mediated silencing of microRNA-874 is a promising diagnosis and prognostic marker in breast cancer

et al. 2017

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“…A previous study demonstrated that miR-874 was downregulated in osteosarcoma and inhibits osteosarcoma cell proliferation and metastasis ( 14 ). Therefore, it was speculated that the specific genes suppressed by miR-874 may predominantly function in this process.…”

Section: Resultsmentioning

confidence: 99%

“…A previous study reported that miR-874 inhibited osteosarcoma progression ( 14 ). Therefore, the present study aimed to determine whether miR-874 promotes the proliferation of osteosarcoma cells by targeting CDK9.…”

Section: Resultsmentioning

confidence: 99%

“…It has been reported that miR-874 can suppress cell migration and invasion by targeting its target genes ( 13 ). Previously, miR-874 was reported to be significantly downregulated in osteosarcoma cell lines and clinical specimens, and the decreased miR-874 expression was significantly associated with large tumor size, distant metastasis and advanced clinical stage, and was an independent predictor of poor survival ( 14 ). However, little is known about the mechanism of miR-874 in osteosarcoma proliferation and invasion.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-874 inhibits cell proliferation and invasion by targeting cyclin‑dependent kinase 9 in osteosarcoma

et al. 2018

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MicroRNAs (miRNAs) perform important roles in the development and progression of human malignancy. miR-874, as a tumor suppressor, is decreased in malignant tumors, including osteosarcoma. However, the potential mechanism of miR-874 in osteosarcoma remains largely unknown. In the present study, a dual-luciferase reporter system supported cyclin-dependent kinase 9 (CDK9) as a direct target gene of miR-874. miR-874 mimics evidently repressed CDK9 expression in osteosarcoma. Furthermore, osteosarcoma tissues and cell lines exhibited increased expression of CDK9, and CDK9 expression levels were inversely correlated (R=−0.725) with that of miR-874 in osteosarcoma tissues. Finally, CDK9 overexpression reversed the potential effect of miR-874 on the proliferation and invasion of osteosarcoma cells. Overall, the results revealed that miR-874, as a tumor suppressor, is involved in osteosarcoma progression and metastasis by targeting CDK9, indicating that the miR-874/CDK9 pathway may serve as a potential therapeutic target for the treatment of osteosarcoma.

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“…Dysregulation of miR-874-3p has been reported to be implicated in several disorders, including intestinal barrier dysfunction, skeletal anabolism, allergic rhinitis, asthma, myogenesis and cognitive impairment ( 62 – 68 ), as well as in the progression and metastasis of several malignancies, such as osteosarcoma, breast, gastric and lung cancer, and head and neck squamous cell carcinoma ( 69 – 76 ). Furthermore, emerging evidence indicates that miR-874-3p is downregulated in CRC and upregulation of miR-874-3p inhibits growth, induces apoptosis and reverses chemoresistance in CRC ( 77 – 79 ).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR-874-3p promotes chemotherapeutic resistance in colorectal cancer via inactivation of the Hippo signaling pathway

et al. 2017

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Overcoming resistance to chemotherapy is an arduous challenge in the treatment of colorectal cancer (CRC), particularly since the underlying molecular mechanisms remain obscure. In the present study, we reported that miR-874-3p was markedly downregulated in CRC tissues compared with that in adjacent normal colorectal epithelial tissues. Upregulation of miR-874-3p attenuated the chemoresistance of CRC cells to 5-fluorouracil (5-FU) in vitro and in vivo. Conversely, inhibition of miR-874-3p yielded an opposite effect. Furthermore, our results demonstrated that miR-874-3p directly inhibited the expression of transcriptional co-activators YAP and TAZ of the Hippo signaling pathway, resulting in the inactivation of the TEAD transcription. Thus, our findings clarify a novel mechanism by which miR-874-3p restores chemotherapeutic sensitivity of CRC to 5-FU, indicating that offering miR-874-3p mimics in combination with 5-FU may serve as a new therapeutic strategy to circumvent the chemoresistance in CRC.

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Decreased expression of tumor suppressive miR-874 and its clinical significance in human osteosarcoma

Cited by 14 publications

References 21 publications

DNA methylation mediated silencing of microRNA-874 is a promising diagnosis and prognostic marker in breast cancer

DNA methylation mediated silencing of microRNA-874 is a promising diagnosis and prognostic marker in breast cancer

MicroRNA-874 inhibits cell proliferation and invasion by targeting cyclin‑dependent kinase 9 in osteosarcoma

Downregulation of miR-874-3p promotes chemotherapeutic resistance in colorectal cancer via inactivation of the Hippo signaling pathway

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