MiR-125b promotes proliferation and migration of type II endometrial carcinoma cells through targeting TP53INP1 tumor suppressor in vitro and in vivo

Differential expression of miR-125b was detected between type II EC cells (KLE, AN3CA) with ER negative and type I EC cells (ishikawa, RL95-2) with ER positive by qRT-PCR and northern blotting. The effects of miR-125b of on proliferation, migration, and target protein expression were evaluated by CCK8 assay, wound healing assay, transwell migration assay, western blotting, and Tumorigenicity assays in nude mice. In addition, luciferase reporter plasmid was constructed to demonstrate the direct target of miR-125b.MiR-125b was overexpressed in type II EC cells compared with type I. Exogenous miR-125b expression increased proliferation and migration of ishikawa cells and abrogating expression of miR-125b suppressed proliferation, and migration of AN3CA cells in vitro. In addition, in vivo tumor formation assay confirmed that forced miR-125b expression promoted proliferation potential of ishikawa cells, and tumor suppressor gene Tumor Protein 53-Induced Nuclear Protein 1 (TP53INP1) was identified to be the direct target of miR-125b.TP53INP1 was newly identified to be the direct downstream target of miR-125b. MiR-125b, which was overexpressed in type II EC cells compared with type I, contributes to malignancy of type II EC possibly through down-regulating TP53INP1.Endometrial carcinoma (EC) is one of the most common gynecologic malignancies and it is totally classified into two subtypes referred to as type I and type II EC [1]. Type I EC, occurring in ~85% of patients, often displays ER positive. Tumors with this type tend to be well differentiated, of low grade and good prognosis. In contrast, type II, consisting mostly of serous and clear cell carcinoma, typically arises in atrophic endometrium via a mechanism unrelated to estrogen exposure. This type is usually ER negative, and poorly differentiated, of high grade and poor prognosis. Although type II ECs account for approximately 15% of cases, they are responsible for about 50% of all relapses [2]. Great progress was