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Trophoblastic dysfunction, such as insufficient migration and invasion, is well-known to be correlated with preeclampsia (PE). Recently, microRNAs (miRNAs) have been implicated in diverse biological processes and human diseases, including PE. However, the expression and functions of miRNAs in the progression of PE, especially in the regulation of trophoblast cell migration and invasion remain largely unclear. Here, we compared the miRNAs expression profiles of PE patients with healthy controls using microarray assay and chose a significant increased miRNA-miR-34a-5p for further investigation. Overexpression of miR-34a-5p dramatically reduced migration and invasion in trophoblast HTR-8/SVneo cells, whereas enhanced by its inhibitor. Luciferase activity assay showed that miR-34a-5p directly target Smad family member 4 (Smad4), which is associated with cancer cell invasiveness and metastasis. We also found that Smad4 was down-regulated in PE patients, and an inverse relationship between Smad4 and miR-34a-5p expression levels was observed in placental tissues from PE patients. Further study showed that knockdown of Smad4 effectively attenuated the promoting effects of miR-34a-5p inhibition on the migration and invasion of HTR-8/SVneo cells. Taken together, these findings suggest that inhibition of miR-34a-5p improves invasion and migration of trophoblast cells by directly targetting Smad4, which indicated the potential of miR-34a-5p as a therapeutic target against PE. [ABSTRACT FROM AUTHOR]

PI3K/Akt/mTOR signaling pathway plays an important role in tumor development. mTOR overexpression and PI3K/Akt/mTOR signaling pathway enhancement were found in endometrial cancer (EC). MiR-101 was found downregulated in EC. Bioinformatics analysis showed the binding site between miR-101 and the 3'-UTR of mTOR mRNA. This study investigated the role of miR-101 in affecting EC proliferation, apoptosis, and invasion, and mediating mTOR expression. EC tumor tissue and normal endometrial tissue were collected from Jinan maternity and child care hospital. MiR-101 and mTOR expressions were detected. The targeted relationship between miR-101 and mTOR was tested by dual-luciferase reporter gene assay. MiR-101, mTOR, p-mTOR, and p-4EBP1 expressions between HEEC and HEC-1A cells were compared. HEC-1A cells were cultured in vitro and divided into five groups, including miR-NC, miR-101 mimic, si-NC, si-mTOR, and miR-101 + si-mTOR. mTOR, pmTOR, and p-4EBP1 expressions were compared. Cell apoptosis was evaluated by flow cytometry. Cell malignant proliferation was evaluated by colony formation assay. Cell invasion was determined by Transwell assay. MiR-101 and mTOR expressions significantly declined in EC tissue compared with normal endometrium. MiR-101 showed targeted relationship with mTOR. MiR-101 reduced, while mTOR, p-mTOR, and p-4EBP1 levels elevated in HEC-1 cells compared with HEEC cells. MiR-101 mimic and/or si-mTOR transfection obviously reduced mTOR, p-mTOR, and p-4EBP1 expressions, decreased colony formation, decreased invasion, and enhanced apoptosis in HEC-1A cells. MiR-101 downregulated and mTOR elevated in EC tissue. MiR- 101 decreased HEC-1A cell proliferation and invasion, and upregulated apoptosis through targeting mTOR to attenuate PI3K/Akt/mTOR signaling pathway activity. [ABSTRACT FROM AUTHOR]