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.
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.
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.
The plasma expression of the miR-21, miR-155, and miR-10b was significantly increased and the Let-7a plasma expression decreased in the breast cancer patients compromised to the control ones.
We found that the multi-tyrosine kinase inhibitor linifanib could significantly inhibit miR-10b and reverse its oncogenic function in breast cancer and liver cancer both in vitro and in vivo.
The set of miRNAs hsa-mir-146a, hsa-mir-93, hsa-mir-375, hsa-mir-205, hsa-mir-15a, hsa-mir-21, hsa-mir-20a, hsa-mir-503, hsa-mir-29c, hsa-mir-497, hsa-mir-107, hsa-mir-125a, hsa-mir-200c, hsa-mir-212, hsa-mir-429, hsa-mir-34a, hsa-let-7c, hsa-mir-92b, hsa-mir-33a, hsa-mir-15b, hsa-mir-224, hsa-mir-185 and hsa-mir-10b integrate a profile that critically regulates the expression of the mRNA coding for Smad7 in breast cancer.
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.
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.
This was supported by analysis of breast cancer cells, which showed that loss of E-cadherin in metastatic cells is accompanied by elevation of miR-10b and interestingly, by a marked increase in accumulation of c-Jun.
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.
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.
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.
We found that differential miRNA expression in breast cancer could be variable between Lebanese and Western populations. miR-10b was positively correlated with the ER and PR status and miR-155 could be a noteworthy biomarker for the menopausal state, age at diagnosis, PR and Her2 status.
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.
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).
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.
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).