miR-34a is downregulated in human osteosarcoma stem-like cells and promotes invasion, tumorigenic ability and self-renewal capacity

Zou, Yonggen; Huang, Yurong; Yang, Jiexiang; Wu, Jian; Luo, Cheng

doi:10.3892/mmr.2017.6187

Cited by 31 publications

(32 citation statements)

References 24 publications

(35 reference statements)

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“…miR-34a-5p [13] and miR-20a-5p [14] can increase the chemosensitivity of osteosarcoma cells; miR-34a inhibits tumor invasion and metastasis of osteosarcoma by affecting C-IAP2 and Bcl-2 [15]. In addition, miR-34a can also reduce the self-renewal ability, tumorigenic activity and invasive ability of cancer stem cells [16]. miRNA-218 inhibits osteosarcoma cell migration and invasion by down-regulating TIAM1, MMP2 and MMP9 [17].…”

Section: Discussionmentioning

confidence: 99%

The study of mechanism of miR-34c-5p targeting FLOT2 to regulate proliferation, migration and invasion of osteosarcoma cells

Wang

Tang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Objective: Osteosarcoma is one of the most common malignancies in children and adolescents. Studies have shown that miR-34c-5p is involved in the progression of various cancers. To explore the effects of miR-34c-5p on the proliferation, migration and invasion of osteosarcoma cells and its potential mechanism. Methods: qRT-PCR was used to detect the expression levels of miR-34c-5p and FLOT2 mRNA in osteosarcoma tissues and cells. Western Blot was used to detect protein expression. MTT assay used to detect cell viability. Transwell was used to detect cell migration and invasion in each group. Dual luciferase reporter gene assay was used to detect luciferase activity. Results: The expression of miR-34c-5pwas significantly decreased in osteosarcoma tissues and cells and the expression level of FLOT2 mRNA was significantly increased. Overexpression of miR-34c-5p and inhibition of FLOT2 inhibited the proliferation, migration and invasion of osteosarcoma cells and inhibited the expression of Cyclin D1, MMP-2 and MMP-9 proteins and promoted the expression of p21 protein. miR-34c-5p targeted to regulate the expression of FLOT2. Overexpression of FLOT2 reversed the inhibitory effect of miR-34c-5p overexpression on proliferation, migration and invasion of osteosarcoma cell lines. Conclusion: miR-34c-5p can inhibit the proliferation, migration and invasion of osteosarcoma cells. The mechanism may be related to targeting FLOT2, which will provide a new target for the prevention and treatment of osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

The study of mechanism of miR-34c-5p targeting FLOT2 to regulate proliferation, migration and invasion of osteosarcoma cells

Wang

Tang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…Studies have suggested miRNAs could either suppress or promote tumor initiation and progression [12][13][14]. MiR-34a, an miRNA well-studied for its association with tumorigenesis, is commonly downregulated in multiple cancers, including osteosarcoma [15], colorectal carcinoma [16], prostate cancer, [17] and liver cancer [18]. A number of reports have demonstrated that reexpression of miR-34a reduces malignancy potential in many cancer cell types [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

“…MiR-34a, an miRNA well-studied for its association with tumorigenesis, is commonly downregulated in multiple cancers, including osteosarcoma [15], colorectal carcinoma [16], prostate cancer, [17] and liver cancer [18]. A number of reports have demonstrated that reexpression of miR-34a reduces malignancy potential in many cancer cell types [15][16][17]. It is noteworthy that miR-34a inhibits cancer stem cells in osteosarcoma and colorectal cancer [15,16].…”

Section: Introductionmentioning

confidence: 99%

The DNMT1/miR-34a/FOXM1 Axis Contributes to Stemness of Liver Cancer Cells

Cao

Liu

Cao

et al. 2020

Journal of Oncology

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Background. Whether DNA methyltransferase 1 (DNMT1)/miR-34a/FoxM1 signaling promotes the stemness of liver cancer stem cells (LCSCs) remains unclear. This study aimed to assess whether methylation-based silencing of miR-34a by DNMT1 contributes to stemness features via FoxM1 upregulation in LCSCs. Methods. The CD133+ subgroup of MHCC97H cells sorted by MACS was used as LCSCs. DNMT1, BMI1, SOX2, and OCT4 mRNA levels, and miR-34a amounts were determined by qRT-PCR. DNMT1, CD44, and FoxM1 proteins were analyzed by immunoblot. Sphere and colony formation abilities were detected by respective assays. CD133+ cell percentages were assessed by flow cytometry. In vivo oncogenicity was evaluated using a tumor xenograft model in mice. The effects of DNMT1/miR-34a signaling on the stemness of LCSCs were examined by knockdown or overexpression of DNMT1 and/or transfection of miR-34a mimic or inhibitor using lentivirus-delivery systems. FoxM1 association with miR-34a was detected by a reporter assay. Results. We here showed that LCSCs exhibited elevated DNMT1 activity and expression, lower miR-34a expression with higher promoter methylation, and stronger stemness, compared with the parental liver cancer cells. DNMT1 knockdown repressed DNMT1, increased miR-34a amounts by promoter demethylation, and reduced stemness in LCSCs, whereas DNMT1 overexpression had the opposite effects in liver cancer cells. Transfection with miR-34a mimic repressed the stemness of LCSCs, while miR-34a inhibitor significantly downregulated miR-34a and enhanced stemness, without affecting DNMT1 in liver cancer cells. MiR-34a mimic rescued the effects of DNMT1 overexpression on the stemness of LCSCs, without affecting DNMT1 expression. Finally, FOXM1 was identified as a direct target by miR-34a in LCSCs. Conclusions. We revealed that aberrant activation of DNMT1 causes miR-34a promoter methylation and suppression, leading to FoxM1 upregulation by disinhibition and promotion of LCSC stemness. These findings suggest that blockage of DNMT1/miR-34a-mediated FOXM1 upregulation might suppress liver cancer by targeting LCSCs.

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“…miR-34a targets include transcripts coding for proteins that control cell proliferation and survival, and its expression in most normal cell types promotes growth arrest, senescence, or apoptosis [151]. While miR-34a is downregulated in many cancer types [152][153][154], we observed that miR-34a is more abundant in HTLV-1-infected cell lines and in ATLL cells compared to control CD4+ cells [136,155], and provided evidence that both p53 and NF-κB promote miR-34a expression in the context of HTLV-1 infection [136]. Experiments performed using a miR-34a 'sponge' construct and a synthetic miR-34 mimic provided evidence that abundant miR-34a levels provide a survival advantage to HTLV-1-infected cells, in part by controlling the expression of the pro-apoptotic BCL2 family member Bax [136].…”

Section: Deregulation Of Mirna Expression By Tax-1 and Hbzmentioning

confidence: 99%

NF-κB and MicroRNA Deregulation Mediated by HTLV-1 Tax and HBZ

et al. 2019

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The risk of developing adult T-cell leukemia/lymphoma (ATLL) in individuals infected with human T-cell lymphotropic virus 1 (HTLV-1) is about 3–5%. The mechanisms by which the virus triggers this aggressive cancer are still an area of intensive investigation. The viral protein Tax-1, together with additional regulatory proteins, in particular HTLV-1 basic leucine zipper factor (HBZ), are recognized as relevant viral factors required for both viral replication and transformation of infected cells. Tax-1 deregulates several cellular pathways affecting the cell cycle, survival, and proliferation. The effects of Tax-1 on the NF-κB pathway have been thoroughly studied. Recent studies also revealed the impact of Tax-1 and HBZ on microRNA expression. In this review, we summarize the recent progress in understanding the contribution of HTLV-1 Tax- and HBZ-mediated deregulation of NF-κB and the microRNA regulatory network to HTLV-1 pathogenesis.

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miR-34a is downregulated in human osteosarcoma stem-like cells and promotes invasion, tumorigenic ability and self-renewal capacity

Cited by 31 publications

References 24 publications

The study of mechanism of miR-34c-5p targeting FLOT2 to regulate proliferation, migration and invasion of osteosarcoma cells

The study of mechanism of miR-34c-5p targeting FLOT2 to regulate proliferation, migration and invasion of osteosarcoma cells

The DNMT1/miR-34a/FOXM1 Axis Contributes to Stemness of Liver Cancer Cells

NF-κB and MicroRNA Deregulation Mediated by HTLV-1 Tax and HBZ

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