MicroRNA-184 Modulates Doxorubicin Resistance in Osteosarcoma Cells by Targeting BCL2L1

Lin, Bochuan; Huang, Dong; Yu, Cui; Mou, Yong; Liu, Yuan-hang; Zhang, Dawei; Shi, Feng-jun

doi:10.12659/msm.896451

Cited by 37 publications

(25 citation statements)

References 30 publications

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“…The proteins, Bcl-2 and Bax have functions as anti-apoptosis and pro-apoptosis molecules, respectively. Their mutual antagonism influences the direction of apoptosis (15). In our study, the relative expression levels of caspase-3 and Bax mRNA in control group and low expression group remained relatively unchanged, and the level of Bcl-2 increased, while in the overexpression group, the relative expression levels of caspase-3 and Bax mRNA increased, and the level of Bcl-2 decreased.…”

Section: Discussionmentioning

confidence: 99%

The metastasis suppressor gene KISS-1 regulates osteosarcoma apoptosis and autophagy processes

Yin

Tang

Shi

2017

Molecular Medicine Reports

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The expression of the metastasis suppressor gene KISS-1 in osteosarcoma cells during apoptosis and autophagy was evaluated. MG-63 osteosarcoma cells were transfected with either KISS-1 overexpression or KISS-1 knockdown expression vector in vitro, and compared with cell lines transfected with empty vector. After 12, 24, 48 and 72 h of cell culture, the cell proliferation was examined. The MTT method was used to detect apoptosis by flow cytometry, and the mRNA levels of apoptosis and autophagy markers caspase-3, Bcl-2, Bax, LC3 and Beclin1 were assessed by RT-PCR. Our results showed that cells in the control and low expression group kept proliferating during the cell culture period of 72 h, while the cells in the overexpression group progressively decreased in number. Also, the proliferation rate of the low expression group was significantly higher than that of the control group. The relative mRNA expression levels of caspase-3 and Bax mRNA in the control and low expression group showed no change (the expression was lowest in the low expression group). Moreover, the mRNA level of Bcl-2 increased in both cell groups. The mRNA expression levels of caspase-3 and Bax in the overexpression group were increased, and the level of Bcl-2 was reduced significantly. At the same time, the relative expression level of LC3 and Beclin1 mRNA in the control and low expression groups remained the same, and that of the overexpression group increased. The mRNA levels of LC3 and Beclin1 in the overexpression group were the highest, and that of the low expression group the lowest. The differences were statistically significant (P<0.05). Based on these results, we showed that KISS-1 inhibited the proliferation of osteosarcoma in vitro, probably by accelerating the processes of apoptosis and autophagy in the cells.

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Section: Discussionmentioning

confidence: 99%

The metastasis suppressor gene KISS-1 regulates osteosarcoma apoptosis and autophagy processes

Yin

Tang

Shi

2017

Molecular Medicine Reports

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“…Sun and Pei (34) revealed that BCL2L1 is a target of miR-66 and increases vulnerability to propofol treatment in developing astrocytes. Lin et al (35) indicated that BCL2L1 was a target gene of miR-184 and that the miR-184 antagomir promoted apoptosis of osteosarcoma cells.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miRNA‑663b protects against hypoxia‑induced injury in cardiomyocytes by targeting BCL2L1

Sun

et al. 2020

Exp Ther Med

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In the present study, the role of microRNA-663b (miR-663b) in cardiomyocyte injury was examined. Reverse transcription-quantitative PCR (RT-qPCR) was performed to detect miR-663b expression in hypoxia-induced H9c2 cells. The results revealed that miR-663b expression was significantly upregulated in hypoxia-induced H9c2 cells compared with control cells. TargetScan analysis and dual-luciferase reporter assays demonstrated that miR-663b directly targeted the B-cell lymphoma 2 like 1 (BCL2L1) gene. RT-qPCR and western blotting data indicated that BCL2L1 expression was significantly downregulated in hypoxia-induced H9c2 cells compared with control cells. Under hypoxic conditions, H9c2 cells were transfected with miR-663b inhibitor, inhibitor control, miR-663b inhibitor + control small interfering (si)RNA or miR-663b inhibitor + BCL2L1-siRNA for 48 h. ELISA against creatine kinase-muscle/brain (CK-MB) and cardiac troponin 1 (cTnI) demonstrated that the miR-663b inhibitor reduced CK-MD and cTnI release and increased mitochondrial viability when compared with hypoxia-treated cells. Additionally, the miR-663b inhibitor significantly increased H9c2 cell viability and decreased cell apoptosis under hypoxic conditions. The results of ELISA further revealed that the miR-663b inhibitor decreased the release of various inflammatory factors, including tumour necrosis factor α, interleukin (IL) 1β and IL-6 in H9c2 cells under hypoxic conditions. These changes were reversed following BCL2L1 knockdown. In conclusion, miR-663b inhibition protected cardiomyocytes against hypoxia-induced injury by targeting BCL2L1 and may potentially be a novel target for the treatment of patients with myocardial infarction.

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“…46 Moreover, some miRNAs regulate osteosarcoma cell apoptosis by targeting TAp73β (a p53-family protein), EZH2, BCL2L1, PI3K, and KLF4, contributing to alternations in the expression of caspase-3 and bcl-2 and chemosensitivity. [47][48][49][50] Thus, regulating apoptosis process may be another key mechanism that miRNAs are involved in chemotherapy response to osteosarcoma.…”

Section: Modulating Apoptosis Pathwaysmentioning

confidence: 99%

“…Moreover, there are elevated miR-146b-5p and miR-184 in chemoresistant osteosarcoma cells. 49,55 The pro-cancer effect and compensatory raise in levels after chemotherapy may explain that miR-146b-5p and miR-184 could suppress apoptosis to exert chemoresistance. Besides, upregulation of miR-21 46 and miR-193a-5p 47 in osteosarcoma cells also shows resistance to anti-tumor drugs.…”

Section: Mirnas Inducing Chemoresistancementioning

confidence: 99%

Potential therapeutic implications of miRNAs in osteosarcoma chemotherapy

2017

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Osteosarcoma is the most common primary bone cancer in young adults and adolescents. Drug resistance is the main cause leading to therapeutical failure. The mechanisms of drug resistance of osteosarcoma have not been fully understood. Notably, recent researches associate microRNA with drug resistance in osteosarcoma cells, raising the awareness that targeting microRNAs may help in chemotherapy success. In this review, we summarize the mechanisms linking microRNAs to drug resistance and ongoing researches on microRNAs in drug response to osteosarcoma. In addition, the therapeutic potential of microRNAs in chemotherapy will also be discussed.

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MicroRNA-184 Modulates Doxorubicin Resistance in Osteosarcoma Cells by Targeting BCL2L1

Cited by 37 publications

References 30 publications

The metastasis suppressor gene KISS-1 regulates osteosarcoma apoptosis and autophagy processes

The metastasis suppressor gene KISS-1 regulates osteosarcoma apoptosis and autophagy processes

Downregulation of miRNA‑663b protects against hypoxia‑induced injury in cardiomyocytes by targeting BCL2L1

Potential therapeutic implications of miRNAs in osteosarcoma chemotherapy

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