The Role of micro RNAs in Breast Cancer Metastasis: Preclinical Validation and Potential Therapeutic Targets

The death toll of non-small cell lung cancer (NSCLC) patients is primarily due to metastases, which are poorly amenable to therapeutic intervention. In this review we focus on miRs associated with metastasis of NSCLC as potential new targets for anti-metastatic therapy. We discuss miRs validated as therapeutic targets by in vitro data, identification of target(s) and pathway(s) and in vivo efficacy data in at least one clinically-relevant metastasis-related model. A few of the discussed miRs correlate with the clinical status of NSCLC patients. Using miRs as therapeutic agents has the advantage that targeting a single miR can potentially interfere with several metastatic pathways. Depending on their mode of action, the corresponding miRs can be up-or downregulated compared to normal matching tissues. Here, we describe therapeutic approaches for reconstitution therapy and miR inhibition, general principles of anti-metastatic therapy as well as current technical pitfalls.

mentioning

confidence: 99%

MicroRNAs as Potential Targets for Therapeutic Intervention With Metastasis of Non-small Cell Lung Cancer

Weidle

Birzele

Nopora

2019

“…It is expected that tumor cells would develop mechanisms to interact with viruses. Gene silencing by microRNAs is another regulatory mechanism engaged in carcinogenesis (39,(42)(43)(44). The observations of virus-cell interaction and gene silencing mechanisms as part of a cell motility relevant to invasiveness (Figure 4C and D), adds another layer of complexity to the regulation of invasiveness.…”

Section: Discussionmentioning

confidence: 97%

Acquisition of Invasiveness by Breast Adenocarcinoma Cells Engages Established Hallmarks and Novel Regulatory Mechanisms

Mousa

El‐Gamal

Marei

et al. 2019

Background/Aim: Proteomics of invasiveness opens a window on the complexity of the metastasis-engaged mechanisms. The extend and types of this complexity require elucidation. Materials and Methods: Proteomics, immunohistochemistry, immunoblotting, network analysis and systems cancer biology were used to analyse acquisition of invasiveness by human breast adenocarcinoma cells. Results: We report here that invasiveness network highlighted the involvement of hallmarks such as cell proliferation, migration, cell death, genome stability, immune system regulation and metabolism. Identified involvement of cell-virus interaction and gene silencing are potentially novel cancer mechanisms. Identified 6,113 nodes with 11,055 edges affecting 1,085 biological processes show extensive rearrangements in cell physiology. These high numbers are in line with a similar broadness of networks built with diagnostic signatures approved for clinical use. Conclusion: Our data emphasize a broad systemic regulation of invasiveness, and describe the network of this regulation.

“…In addition to oncogenesis, miRs are involved in metastasis of different types of cancer. We recently summarized the role of miRs in metastasis of breast-, prostate, non-small cell lung carcinoma and ovarian cancer (30)(31)(32)(33).…”

Section: Micrornas and Their Role In Oncologymentioning

confidence: 99%

Micro RNAs Promoting Growth and Metastasis in Preclinical In Vivo Models of Subcutaneous Melanoma

Weidle

Ausländer

Brinkmann

2020

During the last years a considerable therapeutic progress in melanoma patients with the RAF V600E mutation via RAF/MEK pathway inhibition and immunotherapeutic modalities has been witnessed. However, the majority of patients relapse after therapy. Therefore, a deeper understanding of the pathways driving oncogenicity and metastasis of melanoma is of paramount importance. In this review, we summarize microRNAs modulating tumor growth, metastasis, or both, in preclinical melanoma-related in vivo models and possible clinical impact in melanoma patients as modalities and targets for treatment of melanoma. We have identified miR-199a (ApoE, DNAJ4), miR-7-5p (RelA), miR-98a (IL6), miR-219-5p (BCL2) and miR-365 (NRP1) as possible targets to be scrutinized in further target validation studies.