MicroRNA­4284 promotes gastric cancer tumorigenicity by targeting ten-eleven translocation 1.

ABSTRACT

Increasing evidence has shown that abnormal expression of miR-4284 participates in the progression of several types of cancer. However, the expression and the role of miR­4284 in gastric cancer remain largely unknown. Therefore, in the present study the miR­4284 expression levels in gastric cancer tissues and cell lines, was examined using reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and found that miR­4284 was significantly upregulated in 40 pairs of gastric cancer tissues and five gastric cancer cell lines compared to the corresponding normal tissues and GES­1 cell line. In addition, increased miR­4284 expression was positively associated with TNM stage (P=0.035), distal metastasis (P=0.022) and poor prognosis in gastric cancer patients. Furthermore, the overexpression of miR­4284 expression was shown to promote cell proliferation, clone formation, invasion and migration, while the suppression of miR­4284 expression induced opposite effects. 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 miR­4284. Upregulated miR­4284 decreased the mRNA and protein levels of TET1 in SGC­7901 cells and downregulated miR­4284 increased the mRNA and protein levels of TET1 in AGS cells. In addition, miR­4284 expression was negatively correlated with the TET1 expression in gastric cancer tissues. Moreover, inhibition of TET1 suppressed the effect of miR­4284 inhibitors on cell proliferation in AGS cells. Therefore, data demonstrated that miR­4284 could promote tumor cell growth, migration and invasion by directly targeting TET1 in gastric cancer, which may provide a potential therapeutic target for gastric cancer treatment.