Upregulation of miRNA-10a-5p promotes tumor progression in cervical cancer by suppressing UBE2I signaling.

Cervical cancer (CC) is a common malignant neoplasm in gynecology. There is increasing evidence to suggest that microRNAs (miRNAs) act as crucial regulators of CC. However, whether miR-10a-5p plays a role in CC is under investigation. The aim of this stuy was to assess the miR-10a-5p expression pattern in the development of CC and investigate its downstream target. MiR-10a-5p inhibition decreased CC cell proliferation and impaired CC cell invasion and migration but enhanced apoptosis. UBE2I was a direct target of miR-10a-5p. QRT-PCR results showed a down-regulation of UBE2I in CC cells, opposing miR-10a-5p. Besides, overexpression of miR-10a-5p down-regulated UBE2I. Functional rescue experiments further indicated the miR-10a-5p-UBE2I axis was linked to CC cell growth, apoptosis and metastasis. MiR-10a-5p upregulation promotes cervical cancer development by inhibiting UBE2I. These results also predict that miR-10a-5p may be a potential target for the clinical treatment of CC.IMPACT STATEMENTWhat is already known on this subject? As a widely researched cancer-related miRNA, the overexpression of miR-10a-5p has been verified in various cancers. It has been described in a meta-analysis report that there were 42 miRNAs up-regulated and 21 miRNAs down-regulated in different stages of cervical cancer tissue versus healthy tissue.What do the results of this study add? We verified that miR-10a-5p initiates and promotes tumor cell development by decreasing UBE2I abundance. This miR-10a-5p-mediated post-transcriptional regulation of UBE2I is involved in the tumorigenesis, invasion and migration of human cervical cancer.What are the implications of these findings for clinical practice and/or further research? These findings provide mechanistic insights into how miR-10a-5p regulates cervical cancer hyper-proliferation and metastasis, as well as a new target for clinical treatment. Nevertheless, whether miR-10a-5p/UBE2I axis can be regulated by non-invasive methods need further exploration, which will be the focus of our future research.

MiR-195-5p facilitates the proliferation, migration, and invasion of human trophoblast cells by targeting FGF2.

BACKGROUND: Preeclampsia (PE), the most significant adverse exposure to cardiovascular risk during pregnancy, is one of the three major factors contributing to maternal and fetal mortality and the leading cause of preterm birth. Recently, various miRNAs have been reported to participate in PE occurrence and development. Nevertheless, the regulatory impact of miR-195-5p in PE is still indistinct. METHODS: Quantitative realtime-PCR (qRT-PCR), western blot, and fluorescence in situ hybridization (FISH) assay were performed to examine miR-195-5p and FGF2 expressions in PE serum samples or HTR-8/SVneo and TEV-1 cells. CCK8, flow cytometry, wound scratch, and transwell assays were conducted to determine cell viability, cycle, apoptosis, migration, and invasion. Dual-luciferase reporter assay unveiled the relationship between miR-195-5p and FGF2. Migration-related and invasion-related protein expressions were measured by western blot assay. RESULTS: miR-195-5p was prominently downregulated while FGF2 was increased in serum samples from PE patients and hypoxia-treated human trophoblast cells. FGF2 was predicted as a downstream target of miR-195-5p and targeted association was verified by dual-luciferase reporter assay. Functional experiments elaborated that miR-195-5p could facilitate trophoblast cell proliferation and metastasis but hinder cell cycle and apoptosis. Inversely, overexpressing of FGF2 could reverse the effects of miR-195-5p on trophoblast cell growth. DISCUSSION: miR-195-5p was decreased in PE serum samples and cell lines, serving as a potential biomarker in protecting PE exacerbation by targeting FGF2.

Accelerated postero-lateral spinal fusion by collagen scaffolds modified with engineered collagen-binding human bone morphogenetic protein-2 in rats.

Bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive cytokine that plays a critical role in bone regeneration and repair. However, its distribution and side effects are major barriers to its success as therapeutic treatment. The improvement of therapy using collagen delivery matrices has been reported. To investigate a delivery system on postero-lateral spinal fusion, both engineered human BMP-2 with a collagen binding domain (CBD-BMP-2) and collagen scaffolds were developed and their combination was implanted into Sprague-Dawley (SD) rats to study Lumbar 4-5 (L4-L5) posterolateral spine fusion. We divided SD rats into three groups, the sham group (G1, n = 20), the collagen scaffold-treated group (G2, n = 20) and the BMP-2-loaded collagen scaffolds group (G3, n = 20). 16 weeks after surgery, the spines of the rats were evaluated by X-radiographs, high-resolution micro-computed tomography (micro-CT), manual palpation and hematoxylin and eosin (H&E) staining. The results showed that spine L4-L5 fusions occurred in G2(40%) and G3(100%) group, while results from the sham group were inconsistent. Moreover, G3 had better results than G2, including higher fusion efficiency (X score, G2 = 2.4±0.163, G3 = 3.0±0, p<0.05), higher bone mineral density (BMD, G2: 0.3337±0.0025g/cm3, G3: 0.4353±0.0234g/cm3. p<0.05) and more bone trabecular formation. The results demonstrated that with site-specific collagen binding domain, a dose of BMP-2 as low as 0.02mg CBD-BMP-2/cm3 collagen scaffold could enhance the posterolateral intertransverse process fusion in rats. It suggested that combination delivery could be an alternative in spine fusion with dramatically decreased side effects caused by high dose of BMP-2.