The results of the present study suggest that miR-181b may function as a tumor inhibitor in the development of lung cancer via targeting Sox6 to decrease the proliferation and metastasis of lung cancer cells.
Twist1 overexpression reversed the effect of Sox6 on inhibiting EMT, confirming that the effect of Sox6 on suppressing tumour invasiveness is mediated by the modulation of Twist1 expression.
We found that miR-671 was significantly upregulated in human prostate cancer tissues and cells. miR-671 overexpression promoted prostate cancer cell proliferation, while its downregulation inhibited prostate cancer cell proliferation, as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, colony formation assays, soft agar growth assays, and bromodeoxyuridine (BrdU) incorporation assays. miR-671 directly targets the 3' untranslated region (UTR) of the tumor suppressor SOX6 (encoding SRY (sex determining region Y)-box 6) to inhibit its expression.
It has been confirmed that SOX6 is a tumor suppressor and downregulated in various cancers, including esophageal squamous cell carcinoma, hepatocellular carcinoma, and chronic myeloid leukemia.
Collectively, these results reveal a new mechanism of SOX6-mediated tumor suppression involving p21 upregulation via the p14ARF-HDM2-p53 axis in an HMG domain-dependent manner.
Additionally, the expression of SOX6, determined by immunohistochemistry, was negatively correlated with the tumor stage (P=0.003) and serum AFP (P=0.02).
The tumor-suppressive function of SOX6 was characterized by cell growth, foci formation, wound-healing and cell invasive assays, and tumor xenograft experiment.