Abstrakt

Gynecologic Cancers 2017: Micro-RNA-505 functions as a tumor suppressor in endometrial cancer by targeting TGF-α- Shuo Chen- The First Affiliated Hospital of China Medical University

Shuo Chen

Background: microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are associated with post-transcriptional guideline of quality articulation in multicellular living beings by influencing both the dependability and interpretation of mRNAs. miRNAs are interpreted by RNA polymerase II as a component of topped and polyadenylated essential transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The essential transcript is divided by the Drosha ribonuclease III protein to deliver an around 70-nt stem-circle antecedent miRNA (pre-miRNA), which is additionally separated by the cytoplasmic Dicer ribonuclease to create the develop miRNA and antisense miRNA star (miRNA*) items. The develop miRNA is fused into a RNA-instigated hushing complex (RISC), which perceives target mRNAs through defective base matching with the miRNA and most usually brings about translational restraint or destabilization of the objective mRNA.

MiR-505 has been identified to function as a tumor suppressor in carcinoma. Numerous studies have indicated that miR-505 inhibits cell proliferation by inducing apoptosis and may promote chemo resistance in carcinoma. Expression of miR-505 correlates with established prognostic biomarkers in carcinoma. Moreover, data from mouse models has indicated an association between miR-505 and human basal-type carcinoma . Another study recently provided evidence that miR-505 could suppress the epithelial-mesenchymal transition (EMT) and metastasis in nasopharyngeal carcinoma. However, little is understood about the biological function and target genes of miR-505 in EC.

Endometrial carcinoma (EC) is one of the most lethal gynecologic cancers. Patients frequently have regional or distant metastasis at diagnosis. MicroRNAs are small non-coding RNAs that participate in numerous biological processes. Recent studies have demonstrated that miR-505 is associated with several types of cancer; however, the expression and function of miR-505 have not been investigated in EC.

Methods: miR-505 articulation in ordinary endometrial tissue, endometrial carcinomas were measured by Quantitative converse translation PCR. The endometrial carcinoma cell lines HEC-1B and Ishikawa were each transfected with miR-505 or mixed mirrors, after which cell phenotype and articulation of important atoms were tested. Double luciferase columnist test and a engraft mouse model were utilized to inspect miR-505 and its objective quality TGF-α.

Results: RT-PCR results showed that miR-505 was essentially down regulated in human EC tissues contrasted with ordinary endometrial tissues. In addition, miR-505 articulation was contrarily connected with FIGO (stage I-II versus III-IV), and lymph hub metastasis (negative versus positive). In vitro, over expression of miR-505 essentially stifled EC cell expansion, expanded apoptosis and diminished transient and intrusive movement. A miR-505 restricting site was recognized in the 3′ untranslated area of TGF-α mRNA (TGFA) utilizing miRNA target-distinguishing programming; a double luciferase correspondent test affirmed that miR-505 straightforwardly targets and controls TGFA. RT-PCR and Western-blotching results showed that over expressing miR-505 diminished the declaration of TGF-α and the TGF-α-managed proteins MMP2, MMP9, CDK2, while actuated Bax and severed PARP articulation in EC cells. In vivo, over expression of miR-505 diminished the tumorigenicity and hindered the development of engraft tumors in a mouse model of EC.

Conclusions: Taken together, this study demonstrates that miR-505 acts as tumor suppressor in EC by regulating TGF-α.

Biography: Dr. Shuo Chen, now is a associated research of Department of Gynecology, the First Affiliated Hospital of China Medical University. During the past five years, he had published 12 SCI articles as the first author, with the total IF value 45 points. He got the 1st National Woman and Child Health Science and Technology Award in 2015, and Liaoning Provincial Science and Technology Progress Award in 2015. Besides, he was the host of the National Natural Science Foundation of China (No. 81602266).