MicroRNA-21 Inhibits the Apoptosis of Osteosarcoma Cell Line SAOS-2 via Targeting Caspase 8

Xu, Bin; Xia, Hehuan; Cao, Junming; Wang, Zhihong; Yang, Yongbo; Lin, Yongsheng

doi:10.3727/096504017x14841698396829

Cited by 20 publications

(13 citation statements)

References 31 publications

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“…4E and F , the expression of miR-21-5p was significantly increased compared with the human osteoblast cell line hFOB 1.19 and adjacent normal tissues. This result is consistent with a previous study ( 24 ). Moreover, we examined the potential correlation among the expression levels of XIST and miR-21-5p, and an inverse correlation between XIST and miR-21-5p expression levels was observed ( Fig.…”

Section: Resultssupporting

confidence: 94%

Long non-coding RNA XIST regulates PDCD4 expression by interacting with miR-21-5p and inhibits osteosarcoma cell growth and metastasis

Zhang¹,

Xia

2017

International Journal of Oncology

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lncRNA-X-inactive specific transcript (lncRNA XIST) has been demonstrated to be a tumor suppressor involved in the pathogenesis and development of various cancers. However, the function of XIST and its working mechanism in osteosarcoma (OS) remain enigmatic. Firstly, we determined the expression of XIST in OS tissues and cell lines by quantitative reverse transcription-PCR (qRT-PCR) and explored whether aberrant XIST expression was associated with recurrence and short overall survival. Furthermore, the effects of XIST on osteosarcoma cells were studied by lentivirus mediated overexpression approach in vitro and in vivo. Detection of a set of epithelial-mesenchymal transition (EMT) markers was performed to explore whether XIST is involved in EMT. Finally, we investigated the regulatory mechanism of XIST acting as a competitive endogenous RNA (ceRNA) of miR-21-5p in OS progression and metastasis. lncRNA XIST was significantly downregulated in osteosarcoma tissues and osteosarcoma cells, and associated with recurrence and short overall survival in OS patients. XIST overexpression remarkably inhibited the proliferation of OS cells as well as the xenograft tumor formation in vivo. Both cell invasion and migration were inhibited by XIST overexpression via suppressing the EMT process. These results indicated that XIST functioned as a tumor suppressor in OS. Moreover, we found that miR-21-5p interacted with XIST by directly targeting the miRNA-binding site in the XIST sequence, and qRT-PCR results showed XIST and miR-21-5p could affect each other's expression, respectively. The following assays verified that the tumor suppressor, PDCD4 was a functional target of miR-21-5p in OS cells. Finally, we affirmed that XIST regulated PDCD4 expression by competitively binding to miR-21-5p. XIST inhibited cell proliferation and cell mobility by competitively binding to miR-21-5p and upregulating PDCD4 in OS. Our study demonstrated that lncRNA-XIST, which acts as a miRNA sponge, impedes miR-21-5p to maintain the expression of PDCD4, which contributes to the progression of OS. Our findings suggest that the newly identified XIST/miR-21-5p/PDCD4 axis could be a potential biomarker or therapeutic target for OS.

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Section: Resultssupporting

confidence: 94%

Long non-coding RNA XIST regulates PDCD4 expression by interacting with miR-21-5p and inhibits osteosarcoma cell growth and metastasis

Zhang¹,

Xia

2017

International Journal of Oncology

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“…MicroRNAs are endogenous, small, non-coding RNAs that regulate gene expression through binding to the 3′untranslated region of target mRNAs [3]. MicroRNA-21(miR-21) is considered as an oncogene, and the up-regulation of it has been reported in a wide range of solid and leukaemic cancers such as colon, gastric, breast and pancreatic cancers [4]. Overexpression of miR-21 also inhibited apoptosis in osteosarcoma.…”

Section: Introductionmentioning

confidence: 99%

LncRNA MEG3 influences the proliferation and apoptosis of psoriasis epidermal cells by targeting miR-21/caspase-8

Jia

Zhang

Lü

et al. 2019

BMC Mol and Cell Biol

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BackgroundIt was reported that microRNA-21(miR-21) was differentially expressed in the keratinocytes of psoriasis patients, and it may influence the apoptosis and proliferation of cells. The role of lncRNA maternally expressed gene3 (MEG3), a competing endogenous RNAs of miR-21, in the progression of psoriasis remains unclear. We aimed to unfold the influence of MEG3 and miR-21 on the proliferation and apoptosis of psoriasis epidermal cells.Methods50μg/L TNF-α was used to treat HaCaTs and NHEKs cells for 24 h, and then different experiments were conducted. qRT-PCR were applied for measuring the mRNA level of MEG3, miR-2, and caspase-8, and the protein expression of caspase-8 was measured with western blotting. Flow cytometry was used for assessing apoptosis. Cell proliferation was detected using MTT and colony formation assays. Dual luciferase reporter assay was applied for confirming the binding site between MEG3 and miR-21, miR-21 and Caspase-8.ResultsA cell model for in vitro studying the role of MEG3 in psoriasis pathophysiology was established using HaCaT and HHEKs. MEG3 was significantly down-regulated in HaCaT, HHEKs, and psoriatic skin samples. MEG3 inhibits proliferation and promotes apoptosis of Activated-HaCaT (Act-HaCaT) and Activated-HHEKs (Act- HHEK) by regulating miR-21, and the binding site between MEG3 and miR-21 was identified. We also found that miR-21 could inhibit the level of caspase-8 and identified the binding site between caspase-8 and miR-21. Some down-stream proteins of caspase-8, Cleaved caspase-8, cytc, and apaf-1 were regulated by miR-21 and MEG3.ConclusionMEG3/miR-21 axis may regulate the expression of caspase-8, and further influence the proliferation and apoptosis of psoriasis keratinocyte, Act-HaCaT and Act- HHEK. Therefore, our findings may provide a new thought for the study of pathogenesis and treatment of psoriasis.

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“…Previous studies also reported that HNK induces apoptosis and G 1 cell cycle arrest in various types of cancer cell ( 39 – 42 ). Furthermore, miR-21 has been identified as an important regulator of diverse cellular functions via the regulation of cancer cell growth ( 43 – 45 ). However, the possible molecular mechanism underlying HNK-induced apoptosis of human OS cells requires further research.…”

Section: Discussionmentioning

confidence: 99%

Honokiol suppresses proliferation and induces apoptosis via regulation of the miR‑21/PTEN/PI3K/AKT signaling pathway in human osteosarcoma cells

2018

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Honokiol (HNK) is a small biphenolic compound, which exerts antineoplastic effects in various types of cancer. However, the mechanism underlying the antitumor effects of HNK in osteosarcoma (OS) cells is not yet fully understood. Emerging evidence has indicated that microRNAs (miRNAs/miRs) serve key roles in numerous pathological processes, including cancer. It has previously been reported that Chinese medicinal herbs harbor anticancer properties via modulating miRNA expression. Therefore, the present study aimed to determine whether HNK could suppress OS cell growth by regulating miRNA expression. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis were used to evaluate the cell proliferation and apoptosis in human OS cells after treatment with HNK, respectively. The results demonstrated that HNK inhibits proliferation and induces apoptosis of human OS cells in a dose-dependent manner. Furthermore, HNK-induced apoptosis was characterized by upregulation of proapoptotic proteins, including cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerase and B-cell lymphoma 2 (Bcl-2)-associated X protein, and downregulation of the anti-apoptotic protein Bcl-2. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) verified that HNK was able to induce aberrant expression of miRNAs in human OS cells, and miR-21 was one of the miRNAs that was most significantly downregulated. To further investigate miR-21 function, the present study validated that HNK reduces miR-21 levels in a dose-dependent manner. In addition, restoration of miR-21 expression abrogated the suppressive effects of HNK on OS cells. Luciferase assay and western blot analysis identified that miR-21 inhibits the expression of phosphatase and tensin homolog (PTEN) by directly targeting its 3′-UTR. Notably, HNK was able to suppress the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway; however, it was reactivated by miR-21 overexpression. Taken together, these data indicated that HNK may inhibit proliferation and induce apoptosis of human OS cells by modulating the miR-21/PTEN/PI3K/AKT signaling pathway. Therefore, miR-21 may be considered a potential therapeutic target for the treatment of osteosarcoma with HNK.

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MicroRNA-21 Inhibits the Apoptosis of Osteosarcoma Cell Line SAOS-2 via Targeting Caspase 8

Cited by 20 publications

References 31 publications

Long non-coding RNA XIST regulates PDCD4 expression by interacting with miR-21-5p and inhibits osteosarcoma cell growth and metastasis

Long non-coding RNA XIST regulates PDCD4 expression by interacting with miR-21-5p and inhibits osteosarcoma cell growth and metastasis

LncRNA MEG3 influences the proliferation and apoptosis of psoriasis epidermal cells by targeting miR-21/caspase-8

Honokiol suppresses proliferation and induces apoptosis via regulation of the miR‑21/PTEN/PI3K/AKT signaling pathway in human osteosarcoma cells

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