A role of miR-10b in drug-resistance of breast cancer cells has never been investigated, although its is very well known to influence invasion and metastasis.
Associations between miR-10b expression and validated target transcript levels, and effects of targeted manipulation of miR-10b levels in a primary BC cell line on proliferation and invasion potential, were explored.
Based on the results obtained in the last decade, some miRNAs are emerging as biomarkers of BC for diagnosis (i.e., miR-9, miR-10b, and miR-17-5p), prognosis (i.e., miR-148a and miR-335), and prediction of therapeutic outcomes (i.e., miR-30c, miR-187, and miR-339-5p) and have important roles in the control of BC hallmark functions such as invasion, metastasis, proliferation, resting death, apoptosis, and genomic instability.
Correspondingly, PTEN knockdown increased stem cell markers, whereas AKT inhibitors compromised the self-renewal ability of CSCs and breast cancer cell lines overexpressing miR-10b.
Differences in expression of miRNAs between cancer stages is also analyzed, and a subset of eight miRNAs is found, for which expression is increased in stage II relative to stage I, including hsa-miR-10b-5p, which contributes to breast cancer metastasis.
Enhanced miR-10b expression or silencing of miR-145 clearly revealed that these microRNAs can regulate the functional properties, EMT program and the expression of major matrix components known to be implicated in breast cancer aggressiveness.
From this perspective, we overview here the miR-10b locus and its involvement in cancer, focusing on its role in the establishment (miR-10b*) and spreading (miR-10b) of breast cancer.
Here we demonstrate sensing of single-stranded DNA analogues to their microRNA cousins using miR-10b and miR-21 as templates, both known to be upregulated in breast cancer.
Higher expression of these three genes were significantly correlated with the hazard ratio for breast cancer recurrence (RUNX2: 3.02, 95% CI = 1.50 ~ 6.07; miR-10a: 2.31, 95% CI = 1.00 ~ 5.32; miR-10b: 3.96, 95% CI = 1.21 ~ 12.98).
Hyperthermia-dependent down-regulatory influence on three distinct BC-related microRNAs in vitro generates translational aspects for clinical BC treatment, since the identified microRNAs miR-10b, miR-15b and miR-139 are known to have oncogenic as well as tumour suppressor functions in BC.
In particular, recent studies provide the first functional evidence that overexpression of a specific miRNA, miR-10b, can contribute to the development of metastasis, which can be exploited therapeutically in treating breast cancer metastasis in mice.
It was found that vestibular schwannomas ranked first among the reported cancer types with up-regulated microRNA-10b expression; melanoma ranked first among the reported cancer types with down-regulated microRNA-10b expression; while breast cancer and hepatocellular cancer presented inconsistent microRNA-10b regulation.
Moreover, five long noncoding RNAs that could competitively bind with miR-10b, respectively, named ACTA2-AS1, RP11-384P7.7, RP11-327J17.9, RP11-124N14.3, and RP11-645C24.5, were discovered as an integration signature with great potential in the prediction of survival outcomes in patients with different stages of breast cancer.
On the basis of these findings, it is plausible that reactivation of CCN5 in miR-10b-positive invasive/metastatic breast cancers alone or in combination with current therapeutic regimens could provide a unique, alternative strategy to existing breast cancer therapy.
Only the has-miR-10b involved in breast cancer invasion and metastasis and has-miR-512-3p appeared to be up-regulated (2-3-fold) in all three cell lines.
Our results provide evidences that the addition of miR-10b RERs to the prognostic factors used in clinical routine could improve the prediction abilities for both overall mortality and disease progression in breast cancer patients.
Overall, these results establish that TWIST1 facilitates breast cancer bone metastasis formation through a mechanism dependent of miR-10b, which leads to increase tumor burden and bone destruction.
Patients with non-metastatic HER2(+) breast cancer had higher serum miR-21 median levels than patients with non-metastatic HER2(-) disease (p = 0.044); whereas patients with metastatic HER2(+) breast cancer had higher serum miR-10b median levels than patients with metastatic HER2(-) disease (p = 0.0004).