MicroRNA-203 inhibits proliferation and invasion, and promotes apoptosis of osteosarcoma cells by targeting Runt-related transcription factor 2

Lin, Wenjun; Zhu, Xiongbai; Yang, Shengwu; Chen, Xin; Wang, Lu; Huang, Zhengxiang; Ding, Yewei; Huang, Lintuo; Lv, Chen

doi:10.1016/j.biopha.2017.05.034

Cited by 26 publications

(16 citation statements)

References 38 publications

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“…The re-expression of normal RUNX2 restored migratory ability. On the other hand, it has been shown that miR-203 inhibits the migration and invasion of osteosarcoma cells by targeting RUNX2 mRNA [ 34 ]. In prostate cancer, miR-466, by directly repressing the osteogenic transcription factor RUNX2 , inhibits tumor growth and metastases [ 35 ], highlighting the role of RUNX2 in inducing the malignant phenotype.…”

Section: Discussionmentioning

confidence: 99%

New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration

Deiana

Carbonare

Serena

et al. 2018

Cells

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The mortality rate for malignant melanoma (MM) is very high, since it is highly invasive and resistant to chemotherapeutic treatments. The modulation of some transcription factors affects cellular processes in MM. In particular, a higher expression of the osteogenic master gene RUNX2 has been reported in melanoma cells, compared to normal melanocytes. By analyzing public databases for recurrent RUNX2 genetic and epigenetic modifications in melanoma, we found that the most common RUNX2 genetic alteration that exists in transcription upregulation is, followed by genomic amplification, nucleotide substitution and multiple changes. Additionally, altered RUNX2 is involved in unchecked pathways promoting tumor progression, Epithelial Mesenchymal Transition (EMT), and metastasis. In order to investigate further the role of RUNX2 in melanoma development and to identify a therapeutic target, we applied the CRISPR/Cas9 technique to explore the role of the RUNT domain of RUNX2 in a melanoma cell line. RUNT-deleted cells showed reduced proliferation, increased apoptosis, and reduced EMT features, suggesting the involvement of the RUNT domain in different pathways. In addition, del-RUNT cells showed a downregulation of genes involved in migration ability. In an in vivo zebrafish model, we observed that wild-type melanoma cells migrated in 81% of transplanted fishes, while del-RUNT cells migrated in 58%. All these findings strongly suggest the involvement of the RUNT domain in melanoma metastasis and cell migration and indicate RUNX2 as a prospective target in MM therapy.

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Section: Discussionmentioning

confidence: 99%

New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration

Deiana

Carbonare

Serena

et al. 2018

Cells

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“…As a direct target of miR-18a-5p, IRF2 is a DNA-binding protein belonging to IRFs family ( 30 ). The functions of IRF2 may be complex and remain obscure in human cancers.…”

Section: Discussionmentioning

confidence: 99%

miR‑18a‑5p promotes cell invasion and migration of osteosarcoma by directly targeting IRF2

et al. 2018

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An increasing number of studies have suggested that microRNAs (miRNAs) are involved in the progress of many human cancers including osteosarcoma (OS). Especially, microRNA-18a-5p (miR-18a-5p) has been reported to associate with the occurrence, development and clinical outcomes of human cancers. Therefore, we investigated the functions of miR-18a-5p in OS. Reverse transcription-quantitative PCR (RT-qPCR) showed that miR-18a-5p was significantly upregulated in OS tissues and cell lines (MG-63 and Saos-2). The overexpression of miR-18a-5p was found to significantly promote cell migration and invasion in MG-63 cells via Transwell assay. Moreover, luciferase reporter assays indicated that interferon regulatory factor (IRF)2 was a direct target of miR-18a-5p. IRF2 was downregulated in MG-63 and Saos-2 cell lines. Furthermore, Transwell analysis showed that the knockout of IRF2 promoted cell migration and invasion in MG-63 cells. Carcinogenesis of miR-18a-5p was reversed by the overexpression of IRF2 in OS. In conclusion, miR-18a-5p promoted the invasion and migration of OS cells through inhibiting IRF2 expression. Thus, miR-18a-5p might act as a potential target for the diagnosis and treatment of OS in the future.

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“…An increasing number of studies have reported that miR‐203 is frequently downregulated in numerous types of cancer cells, such as osteosarcoma, colorectal cancer, hepatocellular carcinoma, breast cancer, and NSCLC cells. Changes in the expression of miR‐203 results in antitumor effects, suggesting that miR‐203 plays an important role in regulating tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

miR‐203 inhibits cell proliferation, invasion, and migration of non‐small‐cell lung cancer by downregulating RGS17

et al. 2017

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Involvement of the RGS17 oncogene in the promotion of non‐small‐cell lung cancer (NSCLC) has been reported, but the regulation mechanism in NSCLC remains unclear. MicroRNAs (miRNAs) negatively regulate gene expression, and their dysregulation has been implicated in tumorigenesis. To understand the role of miRNAs in Regulator of G Protein Signaling 17 (RGS17)‐induced NSCLC, we showed that miR‐203 was downregulated during tumorigenesis, and inhibited the proliferation and invasion of lung cancer cells. We then determined whether miR‐203 regulated NSCLC by targeting RGS17. To characterize the regulatory effect of miR‐203 on RGS17, we used lung cancer cell lines, A549 and Calu‐1, and the constructed miR‐203 and RGS17 overexpression vectors. The CCK8 kit was used to determine cell proliferation, and the Transwell® assay was used to measure cell invasion and migration. RT‐PCR, western blots, and immunofluorescence were used to analyze expression of miR‐203 and RGS17, and the luciferase reporter assay was used to examine the interaction between miR‐203 and RGS17. Nude mice were used to characterize in vivo tumor growth regulation. Expression of miR‐203 inhibited proliferation, invasion, and migration of lung cancer cell lines A549 and Calu‐1 by targeting RGS17. The regulatory effect of miR‐203 was inhibited after overexpression of RGS17. The luciferase reporter assay showed that miR‐203 downregulated RGS17 by direct integration into the 3′‐UTR of RGS17 mRNA. In vivo studies showed that expression of miR‐203 significantly inhibited growth of tumors. Taken together, the results suggested that expression of miR‐203 inhibited tumor growth and metastasis by targeting RGS17.

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MicroRNA-203 inhibits proliferation and invasion, and promotes apoptosis of osteosarcoma cells by targeting Runt-related transcription factor 2

Cited by 26 publications

References 38 publications

New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration

New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration

miR‑18a‑5p promotes cell invasion and migration of osteosarcoma by directly targeting IRF2

miR‐203 inhibits cell proliferation, invasion, and migration of non‐small‐cell lung cancer by downregulating RGS17

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