Tumor and control samples significantly (P < 0.05) differed in the expression of miR-23b, miR-1, let-7f, and let-7c in endometrial sarcomas, and miR-1, let-7c, miR-133b, let-7b, miR-143, let-7a, let-7d, let-7e, let-7g, miR-222, let-7i, and miR-214 in mixed epithelial-mesenchymal tumors.
TumormiR-1 levels correlated with the overall survival of patients with NSCLC. miR-1 levels were also lower in endothelial cells isolated from NSCLC tumors and tumor-bearing lungs of KP mouse model.
A tetrazolium assay and a trypan blue exclusion assay revealed that miR‑1 suppressed ESCC cell proliferation and increased apoptosis, whereas the silencing of miR‑1 promoted cell proliferation and decreased apoptosis, suggesting that miR‑1 is a novel tumor suppressor.
Additionally, it was investigated whether miR‑1 and its hub genes were associated with clinical features, including age, tumor status, residual tumor, lymph node metastasis, pathological T stage and prostate specific antigen level.
An age-, sex-, tumor stage and treatment-adjusted multivariate Cox regression analysis revealed that miR-1 serum levels (HR 0.451, 95% CI 0.228-0.856, P=0.015) were independently associated with OS, whereas serum miR-122 was not. miR-1 serum levels showed no relevant correlation with clinical chemistry liver parameters, whereas serum miR-122 correlated with clinical chemistry parameters of hepatic necroinflammation, liver function and synthetic capacity.
As a tumor suppressor miR involved in post-transcriptional regulation of crucial tumor associated gene expression, miR-1 represents a promising target for anticancer therapy.
Expression of miR-1 in nonexpressing A549 and H1299 cells reversed their tumorigenic properties, such as growth, replication potential, motility/migration, clonogenic survival, and tumor formation in nude mice.
Expression of miR-1 and miR-133a was further evaluated in 64 paired tissue samples (CRC tumor and adjacent normal mucosa) using the stem-loop real-time polymerase chain reaction.
Further analysis of novel cancer signaling pathways modulated by the tumor-suppressive cluster miR-1/133a will provide insights into the molecular mechanisms of lung-SCC oncogenesis and metastasis.
However, the relevant downstream effector signals in this axis are unclear. miR-1 was recently shown to function as a tumor suppressor in prostate cancer cells, where its expression correlated with reduced metastatic potential.
In addition to several novel MPM-associated microRNAs, we observed that the expression level of miR-1 was significantly lower in tumors as compared with normal pleural specimens.
In conclusion, our findings indicate that miR-1 acts as a tumor suppressor in prostate cancer by influencing multiple cancer-related processes and by inhibiting cell proliferation and motility.