In addition to CTNNB1-activating mutations, we found inactivating mutations of epigenetic regulators (KDM6A, TET1, BAP1) associated with metastatic disease.
Additionally, luciferase reporter assay was conducted and showed that ten-eleven translocation 1 (TET1), a tumor suppressor gene that regulating cell survival and metastasis, was a direct target of miR‑4284.
As the promoting effects of miR-29b in the proliferation and metastasis of MDA-MB-231 and MCF-7, knockdown of TET1 also led to increased proliferation, colony formation, invasion and EMT.
Collectively, these findings suggest that Tet1 expression plays a critical role in metastasis of lung cancer cells by suppression of invasion and epithelial-mesenchymal transition (EMT).
And we further investigated the expression and functional involvement of TET1 in proliferation, migration and invasion and determined that TET1 may function as a tumor suppressor. miR-29b was proved to inhibit metastasis through the targeting of TET1, indicating that downregulation of miR-29 may involve in HCC carcinogenesis and progression through potentiation of TET1 expression.
Here we show that, in gastric cancers, the 5 hmC decrease correlates with a decrease in ten-eleven translocation 1 (TET1) expression, which is strongly associated with metastasis and poor survival in patients with gastric cancer.
Taken together, these findings indicate that promoter hypermethylation may contribute to the downregulation of TET1 and could be used as a promising marker for diagnosis in patients with breast cancer metastasis.
In particular, TET1 acts as tumor suppressor preventing cell proliferation and tumor metastasis and it has frequently been found down-regulated in cancer.