Exosomal miR-130b-3p targets SIK1 to inhibit medulloblastoma tumorigenesis

Huang, Saihua; Xue, Ping; Han, Xiao; Zhang, Caiyan; Yang, Lan; Liu, Lijuan; Wang, Xiang; Li, Hao; Fu, Jinrong; Zhou, Yufeng

doi:10.1038/s41419-020-2621-y

Cited by 36 publications

(27 citation statements)

References 44 publications

(48 reference statements)

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“…Among these, we focused on SIK1. Previous studies have shown that SIK1 is a tumor suppressor and is regulated by transcription factors in some cancers [ 26 – 29 , 49 ]. We therefore speculated that BMI1 might be involved in regulation of SIK1 expression.…”

Section: Discussionmentioning

confidence: 99%

BMI1 promotes osteosarcoma proliferation and metastasis by repressing the transcription of SIK1

Wang

Lin

et al. 2022

Cancer Cell Int

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Background Osteosarcoma (OS) is the most common malignant tumor of bone, and the clinical efficacy of current treatments and associated survival rates need to be further improved by employing novel therapeutic strategies. Although various studies have shown that BMI1 protein is universally upregulated in OS cells and tissues, its specific role and underlying mechanism have not yet been fully explored. Methods Expression of BMI1 protein in OS cells was detected by western blot. The effect of BMI1 on proliferation and migration of OS cells (143B and U-2OS cell lines) was investigated in vitro using CCK-8, colony formation and transwell assays, and in vivo using subcutaneous tumorigenesis and lung metastasis assays in xenograft nude mice. Expression of epithelial–mesenchymal transition (EMT)-associated proteins was detected by immunofluorescence imaging. Bioinformatic analysis was performed using ENCODE databases to predict downstream targets of BMI1. SIK1 mRNA expression in osteosarcoma cells was detected by quantitative real-time reverse transcription PCR (qPCR). Chromatin immunoprecipitation-qPCR (ChIP-qPCR) was used to investigate expression of BMI1-associated, RING1B-associated, H2AK119ub-associated and H3K4me3-associated DNA at the putative binding region of BMI1 on the SIK1 promoter in OS cells. Results Using both in vitro and in vivo experimental approaches, we found that BMI1 promotes OS cell proliferation and metastasis. The tumor suppressor SIK1 was identified as the direct target gene of BMI1 in OS cells. In vitro experiments demonstrated that SIK1 could inhibit proliferation and migration of OS cells. Inhibition of SIK1 largely rescued the altered phenotypes of BMI1-deficient OS cells. Mechanistically, we demonstrated that BMI1 directly binds to the promoter region of SIK1 in a complex with RING1B to promote monoubiquitination of histone H2A at lysine 119 (H2AK119ub) and inhibit H3K4 trimethylation (H3K4me3), resulting in inhibition of SIK1 transcription. We therefore suggest that BMI1 promotes OS cell proliferation and metastasis by inhibiting SIK1. Conclusions Our results reveal a novel molecular mechanism of OS development promoted by BMI1 and provides a new potential target for OS treatment.

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Section: Discussionmentioning

confidence: 99%

BMI1 promotes osteosarcoma proliferation and metastasis by repressing the transcription of SIK1

Wang

Lin

et al. 2022

Cancer Cell Int

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“… 23 Another study found that exosomal miR-130b-3p targeted serine/threonine-protein kinase 1 through the p53 signal pathway could inhibit medulloblastoma tumorigenesis. 24 As for miR-3614-3p, a study has reported that the overexpression of it can down-regulate the expression of TRIM25 to inhibit the growth of breast cancer cells. 25 MiR-365a-3p was proved to inhibit the expansion and metastasis of colorectal cancer cells partly via inhibiting the expression of ADAM10 and JAK/STAT signal.…”

Section: Discussionmentioning

confidence: 99%

A Novel miRNA-Based Model Can Predict the Prognosis of Clear Cell Renal Cell Carcinoma

Zhang

et al. 2021

Technol Cancer Res Treat

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Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent renal malignant cancer, whose survival rate and quality of life of patients are still not satisfactory. Nevertheless, the TNM staging system currently used in clinical cannot make accurate survival predictions and precise treatment decisions for ccRCC patients. Therefore, there is an urgent need for more reliable biomarkers to identify high-risk subgroups of ccRCC patients to guide timely intervention and treatment. Recently, MiRNAs have been shown to be closely related to the procession of a variety of tumors, and they have high stability in various tissues, which makes them suggested to have the potential as a prognostic biomarker of ccRCC. In this study, by analyzing and processing the miRNAs expression profile of ccRCC patients from the TCGA database, we finally constructed an excellent miRNAs signature and verified it through a variety of methods. In order to build a more accurate and reliable clinical predictive model, we integrated the miRNAs signature with other prognostic-related clinical parameters to construct a nomogram. Functional enrichment analysis showed that miRNAs in the signature may regulate the genes involved in the Hippo signaling pathway, Tight junction, and Wnt signaling pathway to cause different prognoses of ccRCC patients, which may provide a reference for subsequent basic research and targeted therapy. To conclude, our study constructed a useful miRNAs signature, which allows the prognosis stratification for ccRCC patients and thereby guides the timely and effective interventions on high-risk patients. At the same time, this study also found the potential biological pathways involved in the procession of ccRCC.

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“…As a new intracellular communication toll, exosomes play a vital role in tumor progression (Huang et al, 2020; Zhang et al, 2020). Exosomes are considered to be an ideal drug delivery vehicle, which mediate cell‐to‐cell communication by delivering DNAs, RNAs, and proteins.…”

Section: Discussionmentioning

confidence: 99%

Cisplatin‐resistant osteosarcoma cell‐derived exosomes confer cisplatin resistance to recipient cells in an exosomal circ_103801‐dependent manner

Pan

Lin

2020

Cell Biology International

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Studies have shown that exosomes can mediate the chemoresistance of drug‐resistant cells by transmitting circular RNAs (circRNAs). However, the role of exosome‐derived hsa_circ_103801 (exosomal hsa_circ_103801) in osteosarcoma (OS) remains unclear. The level of hsa_circ_103801 was upregulated in the serum exosomes from patients with OS, and OS patients with high hsa_circRNA_103801 expression had a shorter survival time relative to patients with low hsa_circ_103801 expression. The expression of hsa_circ_103801 was upregulated in cisplatin‐resistant MG63 (MG63/CDDP) cells compared with that in MG63 cells. In addition, hsa_circ_103801 was highly enriched in exosomes derived from CDDP‐resistant OS cells and could be delivered to MG63 and U2OS cells through exosomes. Exosomes derived from CDDP‐resistant cells were shown to reduce the sensitivity of MG63 and U2OS cells to CDDP, inhibit apoptosis, and increase the expression of multidrug resistance‐associated protein 1 and P‐glycoprotein. Moreover, exosomal hsa_circ_103801 could strengthen the promotive effect of exosomes on the chemoresistance of MG63 and U2OS cells to CDDP. Hence, serum exosomal hsa_circ_103801 may serve as an effective prognostic biomarker for OS, and exosomal hsa_circ_103801 could be a potential target for overcoming OS chemoresistance.

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Exosomal miR-130b-3p targets SIK1 to inhibit medulloblastoma tumorigenesis

Cited by 36 publications

References 44 publications

BMI1 promotes osteosarcoma proliferation and metastasis by repressing the transcription of SIK1

BMI1 promotes osteosarcoma proliferation and metastasis by repressing the transcription of SIK1

A Novel miRNA-Based Model Can Predict the Prognosis of Clear Cell Renal Cell Carcinoma

Cisplatin‐resistant osteosarcoma cell‐derived exosomes confer cisplatin resistance to recipient cells in an exosomal circ_103801‐dependent manner

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