Dataset Information

Potent and selective effect of the mir-10b inhibitor MN-anti-mir10b in human cancer cells of diverse primary disease origin.

ABSTRACT: Since microRNAs (miRNAs, miRs) have been implicated in oncogenesis, many of them have been identified as therapeutic targets. Previously we have demonstrated that miRNA-10b acts as a master regulator of the viability of metastatic tumor cells and represents a target for therapeutic intervention. We designed and synthesized an inhibitor of miR-10b, termed MN-anti-miR10b. We showed that treatment with MN-anti-miR10b led to durable regression/elimination of established metastases in murine models of metastatic breast cancer. Since miRNA-10b has been associated with various metastatic and non-metastatic cancers, in the present study, we investigated the effect of MN-anti-miR10b in a panel of over 600 cell lines derived from a variety of human malignancies. We observed an effect on the viability of multiple cell lines within each cancer type and a mostly dichotomous response with cell lines either strongly responsive to MN-anti-miR10b or not at all even at maximum dose tested, suggesting a very high specificity of the effect. Genomic modeling of the drug response showed enrichment of genes associated with the proto-oncogene, c-Jun.

SUBMITTER: Yoo B

PROVIDER: S-EPMC6054402 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Potent and selective effect of the mir-10b inhibitor MN-anti-mir10b in human cancer cells of diverse primary disease origin.

Yoo Byunghee B Greninger Patricia P Stein Giovanna T GT Egan Regina K RK McClanaghan Joseph J Moore Anna A Benes Cyril H CH Medarova Zdravka Z

PloS one 20180720 7

Since microRNAs (miRNAs, miRs) have been implicated in oncogenesis, many of them have been identified as therapeutic targets. Previously we have demonstrated that miRNA-10b acts as a master regulator of the viability of metastatic tumor cells and represents a target for therapeutic intervention. We designed and synthesized an inhibitor of miR-10b, termed MN-anti-miR10b. We showed that treatment with MN-anti-miR10b led to durable regression/elimination of established metastases in murine models o ...[more]

PMID: 30028875

Similar Datasets

Project description:Deciphering the molecular mechanisms involved in breast tumorigenesis has been the subject of extensive research in the last years; yet unpredictable response and development of resistance to adjuvant therapies remain major questions in the management of breast cancer patients. The power of miR expression signatures has emerged recently from several studies. Normal and breast tumor tissues can be discriminated by a miR signature as reported by Iorio et al (Iorio et al, 2005). Recent findings have also linked deregulated miR expression to breast cancer metastasis (Adorno et al, 2009; Huang et al, 2008; Tavazoie et al, 2008). Moreover, microRNAs are considering as a powerful tool in diagnosis and prognosis of breast cancer. In our study, we measured microRNA expression profiles from 64 primary breast cancer patients, comprising 56 matched tumor and adjacent peritumoral breast tissues, 5 tumor and 3 peritumor unmatched tissues. Our aim was to identify new microRNAs involved in the process of neoplastic transformation. The microarray data analysis identified, in every subgroup of breast cancers analyzed, a specific subset of microRNAs that were differentially expressed in tumor compared to peritumoral tissues. Among these miRs, we identified two (miR-10b* and miR-139-5p) that were down-regulated and three (miR-425, miR-454 and miR-301a) that were up-regulated for all three subtypes. We further show that microRNA-10b* is a master regulator of breast cancer cell proliferation. Two canonical CpG islands (5kb) upstream from the precursor sequence are hypermethylated in breast cancer tissues analyzed. Ectopic delivery of synthetic microRNA-10b* in breast cancer cell lines or into xenograft mouse breast tumors inhibits cell proliferation and impairs tumor growth in vivo, respectively. We identified and validated in vitro and in vivo three novel target mRNAs of miR-10b*, BUB1, PLK1 and CCNA2 genes, which play a remarkable role in cell cycle regulation and whose high expression in breast cancer patients reduced disease free survival, relapse free survival and metastasis free survival when compared to low expressors. This also suggests that restoration of microRNA-10b* expression might bear therapeutic promise. In exploring the potential involvement of miRs in breast tumorigenesis, we profiled the miRs expression of 64 primary breast cancer patients, comprising 56 matched tumor and adjacent peritumoral breast tissues, 5 tumor and 3 peritumor unmatched tissues, using the Agilent microarray platform. For 14 samples technical replicate were also performed.

Dataset Information

Potent and selective effect of the mir-10b inhibitor MN-anti-mir10b in human cancer cells of diverse primary disease origin.

Publications

Potent and selective effect of the mir-10b inhibitor MN-anti-mir10b in human cancer cells of diverse primary disease origin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets