Many cancers exhibit down-regulation or loss of miR-34a, and synthetic miR-34a supplementation has been shown to inhibit tumor growth <i>in vivo</i> However, the post-transcriptional mechanisms that cause miR-34a loss in cancer are not entirely understood.
The microRNA miR-34a is a tumor suppressor transcript, and its loss has been prominently linked to various human cancers, including malignancies of the brain.
Luciferase activity assay showed that <i>miR-34a-5p</i> directly target Smad family member 4 (Smad4), which is associated with cancer cell invasiveness and metastasis.
The integrative approach uncovered novel miRNA-gene networks (e.g., miR-146 and miR-34 regulating p62 and Beclin1 in autophagy) that might give new insights into the complex regulatory mechanisms of gene expression in AD and cancer.
These multiple roles of miR-34a are maintained in a model of human breast cancer, in which chronic expression of miR-34a in triple-negative mesenchymal-like cells (enriched in cancer stem cells-CSCs) could promote a luminal-like differentiation programme, restrict the CSC pool, and inhibit tumour propagation.
We showed that silica nanoparticles can efficiently deliver miR-34a into normal and cancer epithelial cells grown in culture without major signs of toxicity.
Not only that, numerous preclinical researches revealed the giant potential of miR-34a on cancer therapy through diversiform nano-scaled delivery systems.
For example, ectopic expression of microRNA-34a (miR-34a), a tumor suppressor gene that is a direct transcriptional target of p53 and thus is reduced in p53 mutant tumors, has clear effects on cell proliferation and survival in murine models of cancer.
Our data suggest that miR-34a-3p is an independent biomarker of NMIBC recurrence and a promising candidate for further independent validations as an additional factor to improve predictive value of European Organization for Research and Treatment of Cancer nomogram.
Intravenous delivery of miR-34a mimics has been investigated in clinical trials as a potential treatment for advanced cancers; however, the effect of miR-34a on cancer immune surveillance is controversial.
Statistical analysis suggested a probable role of CD44v6, SYNE1, and miR34a in early stages of the malignancy, whereas a strong association was observed between CD44v6, CD44v10, and miR34a expression with locoregional aggressiveness and histopathological conditions.
Although aberrant expression of miR-34a, an essential tumor suppressor miRNA, has been frequently observed in colon cancer (CCa), whether miR-34a can regulate CCa progression by modulating other facets of this malignancy (such as multidrug resistance, MDR) remains unknown.
Among the 51 DEMs, 19 were significantly enriched in 41 KEGG pathways. hsa-miR-34a-5p was enriched in 15 pathways such as the p53 signaling pathway. hsa-miR-323b-3p was enriched in four pathways such as pathways in cancer.
Our findings suggest that functional loss or suppression of the tumor suppressor CXCL10 due to induction of miR-34a leads to inhibition of the TLR signaling pathway during breast tumorigenesis, providing a novel target for the molecular treatment of breast malignancies.
In this study, we find that a long noncoding RNA transcribed antisense to the miR34a host gene, is critical for miR34a expression and mediation of its cellular functions in multiple types of human cancer.
We conducted a continuous variable, meta-analysis from data found in the cancer literature as well as that provided by the Cancer Genome Atlas (TCGA) to estimate miR-34a expression in HNSCC.
Further exploration on the downstream network of miR-34a identified that blocking plasminogen activator inhibitor-1 (PAI-1) expression could restrain OS dedifferentiation into cancer stem-like cells by downregulating SRY-related-HMG box (Sox) 2.
The developed miR-34a nanoplexes inhibited the breast cancer cell growth as confirmed by MTT assay wherein 28% and 34% cancer cell viability was observed in 4T1 and MCF-7 cells, respectively.