Human homologues of murine miRNA sequences, miR-143 and miR-145, consistently display reduced steady-state levels of the mature miRNA at the adenomatous and cancer stages of colorectal neoplasia.
To search for tumor-associated mutations that could affect processing and expression of mature miRNAs, a panel of 91 cancer-derived cell lines was analyzed for sequence variations in 15 miRNAs implicated in tumorigenesis by virtue of their known target transcripts (let-7 family targeting oncogenic Ras) or their localization to sites of frequent chromosomal instability (miR-143, miR-145, miR-26a-1, and miR-21).
Here, we report that expression of miR-145 and miR-205 was restricted to the myoepithelial/basal cell compartment of normal mammary ducts and lobules, whereas their accumulation was reduced or completely eliminated in matching tumor specimens.
Comparison of the possible combinations of DLBCL-, FL- and LN resulted in specific DLBCL- and FL-signatures, which include miRNAs with previously published function in haematopoiesis (MIRN150 and MIRN155) or tumour development (MIRN210, MIRN10A, MIRN17-5P and MIRN145).
Several miRNAs were differentially expressed between normal tissue and tumor microsatellite subtypes, with miR-145 showing the lowest expression in cancer relative to normal tissue.
This specific silencing of c-Myc by miR-145 accounts at least in part for the miR-145-mediated inhibition of tumor cell growth both in vitro and in vivo.
Restoration of tumour suppressor hsa-miR-145 inhibits cancer cell growth in lung adenocarcinoma patients with epidermal growth factor receptor mutation.
The effects of normalisers on the relative quantity of established oncogenic (miR-21 and miR-31) and tumour suppressor (miR-143 and miR-145) target miRNAs were assessed.
Moreover, our findings support a view that miR-145 re-expression therapy could be mainly envisioned in the specific group of patients with ER-alpha-positive and/or TP53 wild-type tumors.
The putative tumor suppressor miR145 is transcriptionally regulated by TP53 and is downregulated in many tumors; however, its role in prostate cancer is unknown.
According to the predictive and prognostic value of the analyzed miRNAs, a significant correlation between miR-145 expression and tumor regression was seen.
In conclusion, this study demonstrated that miR-145 suppresses tumor growth by inhibition of multiple tumor survival effectors, and more we suppose that miR-145 is potentially useful in the therapy of breast cancers.
After systemic or local application of low molecular weight PEI/miRNA complexes, intact miRNA molecules were delivered into mouse xenograft tumors, where they caused profound antitumor effects. miR-145 delivery reduced tumor proliferation and increased apoptosis, with concomitant repression of c-Myc and ERK5 as novel regulatory target of miR-145.
Our results strongly suggested that miR-145 is a tumor cell differentiation-inducing agent in endometrial carcinoma, and that miR-145 or OCT4 may be useful markers for grading endometrial carcinoma.