Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MicroRNA-34 family in breast cancer: from research to therapeutic potential.

ABSTRACT: MicroRNA (miRNA)-34 family (miR-34s), including miR-34a/b/c, is the most well studied non-coding RNAs that regulate gene expression post-transcriptionally. The miR-34s mediates the tumor suppressor function of p53 in the pathogenesis of breast cancer by targeting different oncogenes. This review focuses on the anti-oncogenic regulation of the miR-34s, emphasizing the major signaling pathways that are involved in the modulation of miR-34s in breast cancer. Moreover, it highlights how epigenetic modification by the p53/miR-34s axis regulates the proliferation, invasiveness, chemoresistance, and sternness of breast cancer. A better understanding of the molecular mechanisms of miR-34s will open new opportunities for the development of novel therapeutic strategies and define a new approach in identifying potential biomarkers for early diagnosis of breast cancer.

SUBMITTER: Imani S

PROVIDER: S-EPMC6216011 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

MicroRNA-34 family in breast cancer: from research to therapeutic potential.

Imani Saber S Wu Ray-Chang RC Fu Junjiang J

Journal of Cancer 20180928 20

MicroRNA (miRNA)-34 family (miR-34s), including miR-34a/b/c, is the most well studied non-coding RNAs that regulate gene expression post-transcriptionally. The miR-34s mediates the tumor suppressor function of p53 in the pathogenesis of breast cancer by targeting different oncogenes. This review focuses on the anti-oncogenic regulation of the miR-34s, emphasizing the major signaling pathways that are involved in the modulation of miR-34s in breast cancer. Moreover, it highlights how epigenetic m ...[more]

PMID: 30405848

Similar Datasets

MicroRNA-34 family: a potential tumor suppressor and therapeutic candidate in cancer.

Project description:MicroRNA-34 (miR-34) has been reported to be dysregulated in various human cancers and regarded as a tumor suppressive microRNA because of its synergistic effect with the well-known tumor suppressor p53. Along with the application of MRX34, the first tumor-targeted microRNA drug which based on miR-34a mimics, on phase I clinical trial (NCT01829971), the significance of miR-34 is increasingly recognized. miR-34 plays a crucial role on repressing tumor progression by involving in epithelial-mesenchymal transition (EMT) via EMT- transcription factors, p53 and some important signal pathways. Not only that, numerous preclinical researches revealed the giant potential of miR-34a on cancer therapy through diversiform nano-scaled delivery systems. Here, we provide an overview about the function of miR-34 in various cancers and the mechanism of miR-34 in tumor-associated EMT. Furthermore, its potential role as a microRNA therapeutic candidate is also discussed. Notwithstanding some obstacles existed, the extensive application prospect of miR-34 on oncotherapy cannot be neglected.

| S-EPMC6360685 | biostudies-literature

MicroRNA-34 Family in Cancers: Role, Mechanism, and Therapeutic Potential.

Project description:MicroRNA (miRNA) are small noncoding RNAs that play vital roles in post-transcriptional gene regulation by inhibiting mRNA translation or promoting mRNA degradation. The dysregulation of miRNA has been implicated in numerous human diseases, including cancers. miR-34 family members (miR-34s), including miR-34a, miR-34b, and miR-34c, have emerged as the most extensively studied tumor-suppressive miRNAs. In this comprehensive review, we aim to provide an overview of the major signaling pathways and gene networks regulated by miR-34s in various cancers and highlight the critical tumor suppressor role of miR-34s. Furthermore, we will discuss the potential of using miR-34 mimics as a novel therapeutic approach against cancer, while also addressing the challenges associated with their development and delivery. It is anticipated that gaining a deeper understanding of the functions and mechanisms of miR-34s in cancer will greatly contribute to the development of effective miR-34-based cancer therapeutics.

| S-EPMC10571940 | biostudies-literature

Kinesin family member 11 is a potential therapeutic target and is suppressed by microRNA-30a in breast cancer.

Project description:Kinesin family member 11 (KIF11) is a plus end-directed kinesin indispensable for the formation of the bipolar spindle in metaphase, where it objects to the action of minus end-directed molecular motors. Here, we hypothesize that KIF11 might be a therapeutic target of breast cancer and regulated by miR-30a. Cell Counting Kit 8 assays were used to investigate cell proliferation. Invasion assays were used to survey the motility of cells. Kaplan-Meier and Cox proportional analyses were employed for this outcome study. The prognostic significance and performance of KIF11 were validated on 17 worldwide independent microarray datasets and two The Cancer Genome Atlas-Breast Invasive Carcinoma sets. microRNA was predicted targeting KIF11 through sequence alignment in microRNA.org and confirmed by coexpression analysis in human breast cancer samples. Dual-luciferase reporter assays were employed to validate the interaction between miR-30a and KIF11 further. Higher KIF11 mRNA levels and lower miR-30a were significantly associated with poor survival of breast cancer patients. Inhibition of KIF11 by small-hairpin RNA significantly reduced the proliferation and invasion capabilities of the breast cancer cells. Meanwhile, downregulation of KIF11 could enhance the cytotoxicity of adriamycin in breast cancer cell lines MCF-7 and MDA-MB-231. A population study also validated that chemotherapy and radiotherapy significantly improved survival in early-stage breast cancer patients with low KIF11 expression levels. Further bioinformatics analysis demonstrated that miR-30a could interact with KIF11 and validated by dual-luciferase reporter assays. Therefore, KIF11 is a potential therapeutic target of breast cancer. miR-30a could specifically interact with KIF11 and suppress its expression in breast cancer.

| S-EPMC7384136 | biostudies-literature

Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34.

Project description:Tumor suppressor microRNAs (miRNA) provide a new opportunity to treat cancer. This approach, "miRNA replacement therapy," is based on the concept that the reintroduction of miRNAs depleted in cancer cells reactivates cellular pathways that drive a therapeutic response. Here, we describe the development of a therapeutic formulation using chemically synthesized miR-34a and a lipid-based delivery vehicle that blocks tumor growth in mouse models of non-small-cell lung cancer. This formulation is effective when administered locally or systemically. The antioncogenic effects are accompanied by an accumulation of miR-34a in the tumor tissue and downregulation of direct miR-34a targets. Intravenous delivery of formulated miR-34a does not induce an elevation of cytokines or liver and kidney enzymes in serum, suggesting that the formulation is well tolerated and does not induce an immune response. The data provide proof of concept for the systemic delivery of a synthetic tumor suppressor mimic, obviating obstacles associated with viral-based miRNA delivery and facilitating a rapid route for miRNA replacement therapy into the clinic.

| S-EPMC2913706 | biostudies-literature

Potential Therapeutic and Prognostic Values of LSM Family Genes in Breast Cancer.

Project description:In recent decades, breast cancer (BRCA) has become one of the most common diseases worldwide. Understanding crucial genes and their signaling pathways remain an enormous challenge in evaluating the prognosis and possible therapeutics. The "Like-Smith" (LSM) family is known as protein-coding genes, and its member play pivotal roles in the progression of several malignancies, although their roles in BRCA are less clear. To discover biological processes associated with LSM family genes in BRCA development, high-throughput techniques were applied to clarify expression levels of LSMs in The Cancer Genome Atlas (TCGA)-BRCA dataset, which was integrated with the cBioPortal database. Furthermore, we investigated prognostic values of LSM family genes in BCRA patients using the Kaplan-Meier database. Among genes of this family, LSM4 expression levels were highly associated with poor prognostic outcomes with a hazard ratio of 1.35 (95% confidence interval 1.21-1.51, p for trend = 3.4 × 10-7). MetaCore and GlueGo analyses were also conducted to examine transcript expression signatures of LSM family members and their coexpressed genes, together with their associated signaling pathways, such as "Cell cycle role of APC in cell cycle regulation" and "Immune response IL-15 signaling via MAPK and PI3K cascade" in BRCA. Results showed that LSM family members, specifically LSM4, were significantly correlated with oncogenesis in BRCA patients. In summary, our results suggested that LSM4 could be a prospective prognosticator of BRCA.

| S-EPMC8508234 | biostudies-literature

Characterizing isomiR variants within the microRNA-34/449 family.

Project description:miR-34/449 microRNAs are conserved regulators of multiciliated cell differentiation. Here, we evidence and characterize expression of two isomiR variant sequences from the miR-34/449 family in human airway epithelial cells. These isomiRs differ from their canonical counterparts miR-34b and miR-449c by one supplemental uridine at their 5'-end, leading to a one-base shift in their seed region. Overexpression of canonical miR-34/449 or 5'-isomiR-34/449 induces distinct gene expression profiles and biological effects. However, some target transcripts and functional activities are shared by both canonical microRNAs and isomiRs. Indeed, both repress important targets that result in cell cycle blockage and Notch pathway inhibition. Our findings suggest that 5'-isomiR-34/449 may represent additional mechanisms by which miR-34/449 family finely controls several pathways to drive multiciliogenesis.

| S-EPMC5363356 | biostudies-literature

Src Family Kinases as potential therapeutic targets for chemotherapy-resistant triple negative breast cancer

Project description:Here we quantified tyrosine phosphorylation (pTyr) mediated signaling networks in chemotherapy sensitive (CS) and resistant (CR) TNBC patient derived xenografts (PDX) to gain novel therapeutic insights. We identified Src Family Kinases (SFKs) as potential therapeutic targets in CR TNBC PDXs. Additionally, we performed pTyr analysis on tumor specimens derived from TNBC patients and observed lower prevalence of SFK driven tumors.

2022-10-13 | PXD034154 | Pride

MicroRNA as a Potential Therapeutic Molecule in Cancer.

Project description:Small noncoding RNAs, as post-translational regulators of many target genes, are not only markers of neoplastic disease initiation and progression, but also markers of response to anticancer therapy. Hundreds of miRNAs have been identified as biomarkers of drug resistance, and many have demonstrated the potential to sensitize cancer cells to therapy. Their properties of modulating the response of cells to therapy have made them a promising target for overcoming drug resistance. Several methods have been developed for the delivery of miRNAs to cancer cells, including introducing synthetic miRNA mimics, DNA plasmids containing miRNAs, and small molecules that epigenetically alter endogenous miRNA expression. The results of studies in animal models and preclinical studies for solid cancers and hematological malignancies have confirmed the effectiveness of treatment protocols using microRNA. Nevertheless, the use of miRNAs in anticancer therapy is not without limitations, including the development of a stable nanoconstruct, delivery method choices, and biodistribution. The aim of this review was to summarize the role of miRNAs in cancer treatment and to present new therapeutic concepts for these molecules. Supporting anticancer therapy with microRNA molecules has been verified in numerous clinical trials, which shows great potential in the treatment of cancer.

| S-EPMC8947269 | biostudies-literature

Characterizing isomer variants in the microRNA-34/449 family

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-06-12 | GSE77252 | GEO

MicroRNA-34a: a potential therapeutic target in human cancer.

Project description:MicroRNAs (miRs) are small noncoding RNAs that negatively regulate gene expression by binding to the three untranslated regions of their target mRNAs. Deregulations of miRs were shown to play pivotal roles in tumorigenesis and progression. Recent research efforts have been devoted to translating these basic discoveries into applications that could improve the therapeutic outcome of patients with cancer. MiR-34a is a highly conserved miR throughout many different species. In humans, there are three homologs (hsa-miR34a, hsa-miR-34b and hsa-miR-34c). Early studies have shown that miR-34a acts as a tumor-suppressor gene by targeting many oncogenes related to proliferation, apoptosis and invasion. In this review, we provide a complex overview of miR-34a, including regulating its expression, its known functions in cancer and future challenges as a potential therapeutic target in human cancers.

| S-EPMC4123066 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data