A Novel Bioengineered miR-127 Prodrug Suppresses the Growth and Metastatic Potential of Triple-Negative Breast Cancer Cells

Umeh-Garcia, Maxine; Simion, Catalina; Ho, Pui Yan; Batra, Neelu; Berg, Anastasia L.; Carraway, Kermit L.; Yu, Aiming; Sweeney, Colleen

doi:10.1158/0008-5472.can-19-0656

Cited by 46 publications

(26 citation statements)

References 60 publications

(75 reference statements)

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“…The diagnostic and prognostic potential of miRNAs for tumors has recently been reported, with a number of miRNAs being used a tumor biomarkers and targeted drugs ( 31 ). Moreover, miRNAs are involved in osteosarcoma-associated signaling pathway regulation, which provides a novel strategy for identifying the molecular mechanisms underlying osteosarcoma ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Thiostrepton and miR‑216b synergistically promote osteosarcoma cell cytotoxicity and apoptosis by targeting FoxM1

Cai

Xiao²,

Shen³

et al. 2020

Oncol Lett

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Osteosarcoma is a common primary bone cancer that there are currently no effective treatment strategies for. Forkhead box M1 (FoxM1) is key in the development of osteosarcoma, and microRNA (miR)-216b serves an antitumor role by targeting FoxM1. Moreover, thiostrepton (TST), a natural thiazole antibiotic, induces antitumor effects and specifically targets FoxM1. Therefore, the present study investigated whether thiostrepton and miR-216b synergistically inhibited osteosarcoma cells by targeting FoxM1. The MTT assay, reverse transcription-quantitative PCR, a dual-luciferase reporter assay and flow cytometry were performed. Compared with the human osteoblast cell line hFOB1.19, miR-216b expression was significantly downregulated in the osteosarcoma cell lines U2OS, MG63 and Saos-2. By contrast, FoxM1 expression was significantly upregulated in osteosarcoma cell lines compared with the hFOB1.19 cell line. The results indicated that miR-216b targeted the 3'-untranslated region of FoxM1. Moreover, the results suggested that miR-216b cooperated with TST to decrease cell cytotoxicity and increase cell apoptosis. In addition, miR-216b cooperated with TST to increase Bax expression and decrease Bcl-2 expression. In conclusion, the combination of TST and miR-216b synergistically promoted osteosarcoma cell cytotoxicity and apoptosis by targeting FoxM1. Therefore, the present study suggested that the combination of TST and miR-216b may serve as a promising therapeutic strategy for osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Thiostrepton and miR‑216b synergistically promote osteosarcoma cell cytotoxicity and apoptosis by targeting FoxM1

Cai

Xiao²,

Shen³

et al. 2020

Oncol Lett

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“…uni-heidelberg.de/). Among these target genes of miR-25-5p, KLK9, WNT3A, FGF18, SRSF4, FIBP, SOX12, TGFBI, and NEDD9 have been reported to participate in the development human cancers (42)(43)(44)(45)(46)(47)(48)(49). Thus, we selected these genes for further investigation.…”

Section: Mir-25-5p Regulates Oscc Cell Proliferation Invasion and Mmentioning

confidence: 99%

Melatonin Inhibits the Progression of Oral Squamous Cell Carcinoma via Inducing miR-25-5p Expression by Directly Targeting NEDD9

Wang¹,

Tao

Mao

et al. 2020

Front. Oncol.

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Melatonin exerts anti-cancer roles in various types of cancers. However, to the best of our knowledge, its role in oral squamous cell carcinoma (OSCC) is unknown. The present study aimed to investigate the role of melatonin and its underlying mechanism in OSCC. MTT, colony formation, wound healing, and transwell invasion assays proved that melatonin played anti-tumor effects in OSCC cells by inhibiting cell viability, proliferation, migration, and invasion in a concentration-dependent manner. The RT-qPCR analysis showed that miR-25-5p was significantly upregulated after melatonin treatment. Further, miR-25-5p might be involved in melatonin-induced inhibitory effects on the biological behavior of OSCC. The expression of miR-25-5p was decreased in tumor tissues and OSCC cells detected by RT-qPCR. MTT assay, colony formation assay, and TUNEL staining indicated miR-25-5p overexpression inhibited OSCC cell viability, proliferation, and induced OSCC cell apoptosis. Furthermore, wound healing, transwell invasion assay, and animal experiments suggested that miR-25-5p might exert suppressive effects on the migration, invasion, and tumor formation of OSCC cells, while miR-25-5p knockdown exhibited the opposite effects in OSCC cells. Bioinformatics analysis, western blot analysis, and luciferase reporter assay suggested that neural precursor cell expressed developmentally downregulated protein 9 (NEDD9) was proved to be a putative target for miR-25-5p. The role of NEDD9 in inhibiting OSCC cell proliferation, invasion, and migration was verified with NEDD9 siRNA transfection. Thus, melatonin exerted anti-proliferative, anti-invasive, and anti-migrative effects on OSCC via miR-25-5p/NEDD9 pathway. Melatonin could be applied as a potential novel drug on treating OSCC.

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“…They lead to the silencing of respective gene expression either by direct degradation of mRNA or inhibition of protein translation [ 11 , 12 ]; miRNAs are involved in a wide range of cancer biology processes, including regulation of target mRNA expression, which promotes tumor growth, apoptosis, progression, metastasis, and immune evasion [ 13 , 14 , 15 , 16 ]. Many studies have reported that miRNAs play key roles in the occurrence and progression of breast cancer [ 17 , 18 , 19 , 20 ]; this has prompted translational studies on miRNAs for breast cancer to be actively conducted [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of MicroRNAs as Diagnostic Biomarkers for Breast Cancer Based on the Cancer Genome Atlas

Kim

2021

Diagnostics

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Breast cancer is the most common cancer among women worldwide. MicroRNAs (miRNAs or miRs) play an important role in tumorigenesis, and thus, they have been identified as potential targets for translational research with diagnostic, prognostic, and therapeutic markers. This study aimed to identify differentially expressed (DE) miRNAs in breast cancer using the Cancer Genome Atlas. The miRNA profiles of 755 breast cancer tissues and 86 adjacent non-cancerous breast tissues were analyzed using Multi Experiment Viewer; miRNA–mRNA network analyses and constructed KEGG pathways with the predicted target genes were performed. The clinical relevance of miRNAs was investigated using area under the receiver operating characteristic curve (AUC) analysis, sensitivity, and specificity. The analysis identified 28 DE miRNAs in breast cancer tissues, including nine upregulated and 19 downregulated miRNAs, compared to non-cancerous breast tissues (p < 0.001). The AUC for each DE miRNA, miR-10b, miR-21, miR-96, miR-99a, miR-100, miR-125b-1, miR-125b-2, miR-139, miR-141, miR-145, miR-182, miR-183, miR-195, miR-200a, miR-337, miR-429, and let-7c, exceeded 0.9, indicating excellent diagnostic performance in breast cancer. Moreover, 1381 potential target genes were predicted using the prediction database tool, miRNet. These genes are related to PD-L1 expression and PD-1 checkpoint in cancer, MAPK signaling, apoptosis, and TNF pathways; hence, they regulate the development, progression, and immune escape of cancer. Thus, these 28 miRNAs can serve as prospective biomarkers for the diagnosis of breast cancer. Taken together, these results provide insight into the pathogenic mechanisms and potential therapies for breast cancer.

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A Novel Bioengineered miR-127 Prodrug Suppresses the Growth and Metastatic Potential of Triple-Negative Breast Cancer Cells

Cited by 46 publications

References 60 publications

Thiostrepton and miR‑216b synergistically promote osteosarcoma cell cytotoxicity and apoptosis by targeting FoxM1

Thiostrepton and miR‑216b synergistically promote osteosarcoma cell cytotoxicity and apoptosis by targeting FoxM1

Melatonin Inhibits the Progression of Oral Squamous Cell Carcinoma via Inducing miR-25-5p Expression by Directly Targeting NEDD9

Identification of MicroRNAs as Diagnostic Biomarkers for Breast Cancer Based on the Cancer Genome Atlas

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