Long non-coding RNA Taurine upregulated gene 1 promotes osteosarcoma cell metastasis by mediating HIF-1α via miR-143-5p

Osteosarcoma is one of the most malignant bone tumors, and its major threats are aggressive invasion and early tumor metastasis, which result in a poor prognosis and high mortality. Accumulating evidence indicates that ginsenoside compound K (CK) has a significant antitumor effect, particularly on the inhibition of proliferation and invasion of numerous human tumors. In the present study, it was revealed that CK inhibited the viability and proliferation of osteosarcoma cells. Moreover, it was demonstrated that CK induced apoptosis and inhibited the migration and invasion of osteosarcoma cells via apoptotic staining, Annexin V/PI staining, and Transwell invasion assays. Furthermore, at the molecular level, the present results confirmed that apoptosis and invasion-related proteins were regulated by CK, which was possibly related to the blockade of the PI3K/mTOR/p70S6K1 signaling pathway. In summary, the present findings indicated that CK inhibited viability and proliferation, induced apoptosis, and inhibited the migration and invasion of osteosarcoma cells through the PI3K/mTOR/p70S6K1 signaling pathway.

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“…radiotherapy and chemotherapy for osteosarcoma in the clinic. Thus, patients usually have a poor prognosis and a high mortality rate (22,23).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside CK induces apoptosis and suppresses proliferation and invasion of human osteosarcoma cells through the PI3K/mTOR/p70S6K1 pathway

et al. 2020

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“…37 lncRNA TUG1 could act as a competing endogenous RNA to abolish the endogenous effect of miR-143-5p in osteosarcoma cells, which inhibited HIF-1α expression. 38 In addition, some mRNAs in the CNC network were indicated to be involved in osteogenesis. For example, SFRP1 was found to have core effect in the network for correlating with eight miRNAs and could activate Wnt signal pathway, 39 and IL15RA was an important component in bone formation.…”

Section: Discussionmentioning

confidence: 99%

microRNA expression profiles and the potential competing endogenous RNA networks in NELL‐1‐induced human adipose‐derived stem cell osteogenic differentiation

Cen

Xia

et al. 2020

J of Cellular Biochemistry

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Studies have indicated that Nel‐like molecule‐1 (NELL‐1) was an osteoblast‐specific cytokine and some specific microRNAs (miRNAs) could serve as competing endogenous RNA (ceRNA) to partake in osteogenic differentiation of human adipose‐derived stem cells (hASCs). The aim of this study was to explore the potential functional mechanisms of recombinant human NELL‐1 protein (rhNELL‐1) during hASCs osteogenic differentiation. rhNELL‐1 was added to osteogenic medium to activate osteogenic differentiation of hASCs. High‐throughput RNA sequencing (RNA‐Seq) was performed and validated by real‐time quantitative polymerase chain reaction. Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed to detect the functions of differentially expressed miRNAs and genes. Coding‐noncoding gene co‐expression network and ceRNA networks were constructed to predict the potential regulatory role of miRNAs. A total of 1010 differentially expressed miRNAs and 1762 differentially expressed messenger RNAs (mRNAs) were detected. miRNA‐370‐3p, bone morphogenetic protein 2 (BMP2), and parathyroid hormone like hormone (PTHLH) were differentially expressed during NELL‐1‐induced osteogenesis. Bioinformatic analyses demonstrated that these differentially expressed miRNAs and mRNAs enriched in Rap1 signaling pathway, PI3K‐Akt signaling pathway, p53 signaling pathway, Glucagon signaling pathway, and hypoxia‐inducible factor‐1 signaling pathway, which were important pathways related to osteogenic differentiation. In addition, miRNA‐370‐3p and has‐miR‐485‐5p were predicted to interact with circ0001543, circ0002405, and ENST00000570267 in ceRNA networks. Based on the gain or loss of functional experiments by transfection, the results showed that miR‐370‐3p was a key regulator in osteogenic differentiation by targeting BMP2 and disturbing the expression of PTHLH, and participated in NELL‐1‐stimulated osteogenesis. The present study provided the primary data and evidence for further exploration on the roles of miRNAs and ceRNAs during NELL‐1‐induced ossification of hASCs.

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“…21 Recently, an increasing number of studies have identified aberrantly expressed miRNAs involved in many aspects of OS progression, such as tumour initiation, drug resistance, and metastasis. 22 miR-375 has been identified as a tumour suppressor and was found to be significantly downregulated in multiple types of cancer, including hepatocellular carcinoma and glioma. 23,24 Liu et al found that downregulated miR-375 could be used as a potential serum biomarker for the diagnosis and the prediction of the prognosis and chemosensitivity of OS.…”

Section: Discussionmentioning

confidence: 99%

<p>A Chemotherapy-Driven Increase in Mcl-1 Mediates the Effect of miR-375 on Cisplatin Resistance in Osteosarcoma Cells</p>

Liu¹,

Yu²,

Yang³

et al. 2019

OTT

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Background: Osteosarcoma (OS) is one of the most difficult cancers to treat due to its resistance to chemotherapy. The essential role played by Mcl-1 in promoting chemoresistance has been observed in a variety of cancers, including OS, while the underlying mechanism remains unclear. Methods: We investigated the expression of Mcl-1 in 42 paired OS specimens obtained before and after adjuvant chemotherapy, and its correlation with clinicopathological characteristics. Loss and gain of function studies were performed to analyze the effects of Mcl-1 modulations on the chemosensitivity, and the mechanism involved in the deregulation of Mcl-1 in OS cells. Results: In OS specimens, the expression of Mcl-1 was significantly upregulated after chemotherapy, and high Mcl-1 expression was associated with poorer overall survival and an increased recurrence rate. Furthermore, we demonstrated that chemotherapy-driven increased Mcl-1 decreased chemosensitivity by promoting tumour proliferation and inhibiting DNA damage. Moreover, Mcl-1 was found to be a direct target of miR-375 in OS cells. The knockdown of Mcl-1 phenocopied miR-375 downregulation, and the overexpression of miR-375 rescued the effects of cisplatin-induced DNA damage mediated by Mcl-1. Conclusion: Our data indicated that chemotherapy-driven increase in the expression of Mcl-1 plays a critical role in chemoresistance, and the intervention of the miR-375/Mcl-1 axis may offer a novel strategy to enhance chemosensitivity in OS treatment.

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Long non-coding RNA Taurine upregulated gene 1 promotes osteosarcoma cell metastasis by mediating HIF-1α via miR-143-5p

Cited by 81 publications

References 46 publications

Ginsenoside CK induces apoptosis and suppresses proliferation and invasion of human osteosarcoma cells through the PI3K/mTOR/p70S6K1 pathway

Ginsenoside CK induces apoptosis and suppresses proliferation and invasion of human osteosarcoma cells through the PI3K/mTOR/p70S6K1 pathway

microRNA expression profiles and the potential competing endogenous RNA networks in NELL‐1‐induced human adipose‐derived stem cell osteogenic differentiation

<p>A Chemotherapy-Driven Increase in Mcl-1 Mediates the Effect of miR-375 on Cisplatin Resistance in Osteosarcoma Cells</p>

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