microRNAs (miRNAs) have been reported to play a crucial role in regulating a variety of genes pivotal for tumor metastasis. miR-126 is well known as one of the angiogenesis regulatory miRNAs.
We found that low miR-126 expression had significant association with advanced TNM stage (P <0.001), distant metastasis (P <0.001), and higher tumor grade (P = 0.001).
Of these microRNAs, miR-126 restoration reduces overall tumour growth and proliferation, whereas miR-335 inhibits metastatic cell invasion. miR-335 regulates a set of genes whose collective expression in a large cohort of human tumours is associated with risk of distal metastasis. miR-335 suppresses metastasis and migration through targeting of the progenitor cell transcription factor SOX4 and extracellular matrix component tenascin C. Expression of miR-126 and miR-335 is lost in the majority of primary breast tumours from patients who relapse, and the loss of expression of either microRNA is associated with poor distal metastasis-free survival. miR-335 and miR-126 are thus identified as metastasis suppressor microRNAs in human breast cancer.
In conclusion, we demonstrated that the loss of tumor suppressor miR-126 in hepatitis B virus-related hepatocellular carcinoma cells contributes to the development of metastases through the upregulated expression of its target gene, ADAM9.
Analysis of matched tissues from the same patient revealed that approximately 70% of the tested patients had similar levels of expression of miR-126 in primary cancer and cancer metastases in both lymph node and distant metastases.
This set includes hsa-miR-182, which was most strongly over-expressed in the lung primary tumors, and hsa-miR-126, which was over-expressed in the metastatic tumors.
Decreased miR-126 expression in cervical cancer was found to be significantly associated with lymphatic invasion (P = 0.002), distant metastasis (P < 0.001), FIGO stage (P = 0.009), and histological grade (P = 0.005).
Ectopic expression of miR-126 in SGC-7901 gastric cancer cells potently inhibited cell growth by inducing cell cycle arrest in G0/G1 phase, migration and invasion in vitro as well as tumorigenicity and metastasis in vivo.
Furthermore, miR-126 was down-regulated in human colon cancer tissue, and its expression was inversely correlated with TNM stage and metastasis of patients.
Strategies restoring miR-126-3p expression or targeting VEGF-A or ADAM9 could restrain growth and metastasis of dabrafenib-resistant melanomas and increase their drug sensitivity.
Potential miR‑126 target genes and the signaling pathways that may be regulated by miR‑126 were then examined. miR‑126 expression was significantly reduced in patients with metastatic RCC compared with patients without metastasis.
Cells transfected with shHOTAIR or miR-126 mimic were subjected to western blot to investigate the role of SDF-1/CXCR4 signaling in HOTAIR mediated proliferation and metastasis.
Specific miRNAs (mir-10, mir-21, mir-155, mir-373, mir-30b, mir-126, mir-17p, mir-335) are associated with tumor metastasis and other clinical characteristics for BC, facilitating identification of individuals who are at risk.