Abstract
BackgroundOur previous studies have identified that miR-125b was overexpressed in type II endometrial carcinoma (EC) cells compared with type I using microRNAs microarray. Although recent studies have shown the important role of miR-125b in several tumors and overexpression of miR-125b in advanced EC, its function in this disease has not yet been defined. In the present study, we tried to confirm the result of microRNAs microarray and further investigated the functions of miR-125b in EC, and tried to find new downstream targets of miR-125b.MethodsDifferential 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.ResultsMiR-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.ConclusionsTP53INP1 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.
Highlights
Our previous studies have identified that miR-125b was overexpressed in type II endometrial carcinoma (EC) cells compared with type I using microRNAs microarray
Differential expression of miR-125b between type I and type II EC cells In our previous work, we found that miR-125b was significantly overexpressed in type II EC cells (KLE and AN3CA) with estrogen receptor (ER) negative compared with type I EC cells (RL95-2 and ishikawa) with ER positive using microRNA microarray
There was a slight increase in expression of miR-125b in AN3CA cells compared with KLE but with no statistical significance
Summary
Our previous studies have identified that miR-125b was overexpressed in type II endometrial carcinoma (EC) cells compared with type I using microRNAs microarray. Recent studies have shown the important role of miR-125b in several tumors and overexpression of miR-125b in advanced EC, its function in this disease has not yet been defined. MicroRNAs profiles have shown that there was much microRNAs expression variation across the different subtypes and stages of carcinogenesis, with data indicating that they may play vital roles in the initiation and progression of human malignancies [8,9]. It has been proved to be one of etiologic factors of leukemia [21] Taken together, these observations suggest that miR-125b may play a vital role in the initiation and progression of cancers
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have