Ablation of miR-10b Suppresses Oncogene-Induced Mammary Tumorigenesis and Metastasis and Reactivates Tumor-Suppressive Pathways

Kim, Jongchan; Siverly, Ashley N.; Chen, Dahu; Wang, Min; Yuan, Yuan; Wang, Yumeng; Lee, Hyemin; Zhang, Jinsong; Muller, William J.; Liang, Han; Gan, Boyi; Yang, Xianbin; Sun, Yutong; You, M. James; Ma, Li

doi:10.1158/0008-5472.can-16-1571

Cited by 77 publications

(70 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These included RHOC1, PTEN, and TBX59. Consistent with the literature, we observed a strong inhibition of the pro-metastatic RHOC in the lungs of animals treated with MN-anti-miR10b and doxorubicin, compared to the control groups (Suppl.…”

Section: Resultssupporting

confidence: 91%

Therapy targeted to the metastatic niche is effective in a model of stage IV breast cancer

Yoo

Kavishwar

Wang

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Treatment of stage IV metastatic breast cancer patients is limited to palliative options and represents an unmet clinical need. Here, we demonstrate that pharmacological inhibition of miRNA-10b - a master regulator of metastatic cell viability – leads to elimination of distant metastases in a mouse model of metastatic breast cancer. This was achieved using the miRNA-10b inhibitory nanodrug, MN-anti-miR10b, which consists of magnetic nanoparticles, conjugated to LNA-based miR-10b antagomirs. Intravenous injection of MN-anti-miR10b into mice bearing lung, bone, and brain metastases from breast cancer resulted in selective accumulation of the nanodrug in metastatic tumor cells. Weekly treatments of mice with MN-anti-miR-10b and low-dose doxorubicin resulted in complete regression of pre-existing distant metastases in 65% of the animals and a significant reduction in cancer mortality. These observations were supported by dramatic reduction in proliferation and increase in apoptosis in metastatic sites. On a molecular level, we observed a significant increase in the expression of HOXD10, which is a known target of miRNA-10b. These results represent first steps into the uncharted territory of therapy targeted to the metastatic niche.

show abstract

Section: Resultssupporting

confidence: 91%

Therapy targeted to the metastatic niche is effective in a model of stage IV breast cancer

Yoo

Kavishwar

Wang

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Kim et al demonstrated that overexpression of miR-10b could promote the proliferation, migration and invasion of breast cancer cell in vitro [31]. Kogo et al manifested that overexpression of miR-218 could suppress the migration and invasion of cervical cancer in vitro [15].…”

Section: Discussionmentioning

confidence: 99%

miR-509-3-5P inhibits the invasion and lymphatic metastasis by targeting PODXL and serves as a novel prognostic indicator for gastric cancer

Zhang

Zhu

Sheng³

et al. 2017

Oncotarget

View full text Add to dashboard Cite

BackgroundOur study aimed to investigate the clinicopathological feature and prognostic role of miR-509-3-5P in gastric cancer, to determine the invasive and metastatic role of miR-509-3-5P in vitro and in vivo and to explore the molecular mechanism between miR-509-3-5P and PODXL.ResultsStrikingly lower miR-509-3-5P expression was detected in gastric cancer tissues with advanced tumor stage, poor differentiation and advanced pT stage, and was regarded as an independent prognostic role for poor prognosis. MiR-509-3-5P expression was markedly down-regulated in gastric cancer cell lines and tissues comparing with normal gastric cell and adjacent normal tissues, respectively. Decreased expression of miR-509-3-5P promoted the colony, migration and invasion abilities of gastric cancer cells in vitro as well as tumorigenesis and lymph node metastasis in vivo. Based on the luciferase assay and tissue microarray, PODXL was regarded as a target gene of miR-509-3-5P.Materials and MethodsThe expression of miR-509-3-5P in gastric cancer patients and its clinicopathological relationships as well as prognostic role was studied employing tissue microarray; qRT-PCR was applied to explore miR-509-3-5P expression in gastric cancer cell lines and samples. Moreover, public database was used to analyze the expression of miR-509-3-5P and PODXL. Functional and molecular mechanism experiments were performed in vitro and in vivo.ConclusionsOverexpression of miR-509-3-5P inhibits the invasion and metastasis of gastric cancer in vitro and in vivo, functioning as a tumor suppressor, by targeting PODXL. More importantly, miR-509-3-5P was downregulated in gastric cancer tissues and may serve as a novel prognostic indicator for gastric cancer.

show abstract

“…Studies with cancer cell transplantation and autochthonous cancer mouse models have demonstrated the causal role of miR-10b in breast cancer initiation, growth, progression and metastasis (21). However, the causality of loss- or gain-of-function of miR-10b in other cancers including melanoma is not known.…”

Section: Resultsmentioning

confidence: 99%

Critical role of miR-10b in BRaf^V600E dependent anchorage-independent growth and invasion of melanoma cells

Datar

Kalpana

Serna

et al. 2018

Preprint

View full text Add to dashboard Cite

26Recent high-throughput-sequencing of cancer genomes has identified oncogenic 27 mutations in the BRaf genetic locus as one of the critical events in melanomagenesis. 28 BRaf encodes a serine/threonine kinase that regulates the MAPK/ERK kinase (MEK) 29 and extracellular signal-regulated kinase (ERK) protein kinase cascade. In normal cells, 30 the activity of BRaf is tightly regulated and is required for cell growth and survival. BRaf 31 gain-of-function mutations in melanoma frequently lead to unrestrained growth, 32 enhanced cell invasion and increased viability of cancer cells. Although it is clear that 33 the invasive phenotypes of BRaf mutated melanoma cells are stringently dependent on 34 BRaf-MEK-ERK activation, the downstream effector targets that are required for 35 oncogenic BRaf-mediated melanomagenesis are not well defined. miRNAs have 36 regulatory functions towards the expression of genes that are important in 37 carcinogenesis. We observed that miR-10b expression correlates with the presence of 38 the oncogenic BRaf (BRaf V600E ) mutation in melanoma cells. While expression of miR-39 10b enhances anchorage-independent growth of BRaf wild-type melanoma cells, miR-40 10b silencing decreases BRaf V600E cancer cell invasion in vitro. Importantly, the 41 expression of miR-10b is required for BRaf V600E -mediated anchorage-independent 42 growth and invasion of melanoma cells in vitro. Taken together our results suggest that 43 miR-10b is an important mediator of oncogenic BRaf V600E activity in melanoma.44 45 46 3 47 48 49 Melanoma is the most aggressive of all the skin cancers. BRaf is a 50 serine/threonine protein kinase that activates the MEK/ERK-signaling pathway. About 51 25-70% of malignant melanomas harbor gain-of-function mutations in the oncogene 52 BRaf (1). Among several BRaf gain-of-function mutations, BRaf V600E is the most 53 common mutation and accounts for nearly 80% of them (1). Not only does BRaf V600E 54 cause a sustained activation of ERK signaling pathway in melanoma, it is also critical for 55 the malignant process and is one of the few identified driver mutations essential for 56 melanoma proliferation and survival. The transformation of melanocytes to melanoma 57 by BRaf V600E requires activation of the MEK-ERK kinases cascade with multiple 58 downstream components (2-4). The mechanism that integrates the diverse components 59 into a coordinated response to the BRaf V600E mutation remains undefined. 60 61 MicroRNAs (miRNAs) are small, non-protein coding RNA molecules and they 62 regulate gene expression through a combination of translational repression and mRNA 63 destabilization (5). Each miRNA targets ~200 mRNA molecules (6). Because of their 64 pleiotropic potentials, miRNAs are attractive candidates as master regulators of the 65 BRaf V600E oncogenic transformation program. In this study, we identified for the first 66 time, significant positive correlation between BRaf V600E mutation and microRNA-10b 67 (miR-10b) expression. Furthermore, we show that miR-10b is a novel ...

show abstract

Ablation of miR-10b Suppresses Oncogene-Induced Mammary Tumorigenesis and Metastasis and Reactivates Tumor-Suppressive Pathways

Cited by 77 publications

References 58 publications

Therapy targeted to the metastatic niche is effective in a model of stage IV breast cancer

Therapy targeted to the metastatic niche is effective in a model of stage IV breast cancer

miR-509-3-5P inhibits the invasion and lymphatic metastasis by targeting PODXL and serves as a novel prognostic indicator for gastric cancer

Critical role of miR-10b in BRaf^V600E dependent anchorage-independent growth and invasion of melanoma cells

Contact Info

Product

Resources

About

Ablation of miR-10b Suppresses Oncogene-Induced Mammary Tumorigenesis and Metastasis and Reactivates Tumor-Suppressive Pathways

Cited by 77 publications

References 58 publications

Therapy targeted to the metastatic niche is effective in a model of stage IV breast cancer

Therapy targeted to the metastatic niche is effective in a model of stage IV breast cancer

miR-509-3-5P inhibits the invasion and lymphatic metastasis by targeting PODXL and serves as a novel prognostic indicator for gastric cancer

Critical role of miR-10b in BRafV600E dependent anchorage-independent growth and invasion of melanoma cells

Contact Info

Product

Resources

About

Critical role of miR-10b in BRaf^V600E dependent anchorage-independent growth and invasion of melanoma cells