Here, we identified the TIC-specific miRNAs, miR-1246 and miR-1290, as crucial drivers for tumour initiation and cancer progression in human non-small cell lung cancer.
Overexpression of miR-1246 in a prostate cancer cell line significantly inhibited xenograft tumor growth <i>in vivo</i> and increased apoptosis and decreased proliferation, invasiveness, and migration <i>in vitro</i> miR-1246 inhibited N-cadherin and vimentin activities, thereby inhibiting epithelial-mesenchymal transition.
Our proteomic approach also revealed that miR-1246 inhibits Cav1 and acts through PDGFβ receptor at the recipient cells to inhibit cell proliferation. miR-1246 inhibitor treatment in combination with chemotherapy led to reduced tumor burden in vivo.
The pro-inflammatory phenotype of miR-1246 in MSCs was independent of TNFα stimulations and mediated by direct targeting of the tumor-suppressors PRKAR1A and PPP2CB.
Importantly, the selectively enriched exosome microRNA, human miR-1246, was detected at significantly higher levels in exosomes isolated from PDX mouse plasma, indicating that tumor exosome microRNAs are released into the circulation and can serve as plasma biomarkers for breast cancer.
Our data showed that the expression of miR-1246 was dramatically decreased in cervical cancer tissue, compared with normal control group (p=0.0012), and miR-1246 was negatively correlated with clinical stage and HPV16E6 infected status (p=0.0410), but no correlation was observed with age, tumor diameter, cervical invasion depth, lymph node metastasis, or vascular invasion (p>0.05).
MicroRNA-1246 in the blood can be used as a good indicator for the diagnosis of malignant tumor diseases and has a moderate diagnostic accuracy for the differentiation of patients with malignant tumors from healthy people.
These results demonstrated that miR-1246 inhibited cell invasion and EMT process by targeting CXCR4 and blocking JAK/STAT and PI3K/AKT signal pathways in lung cancer cells.