Hsa_circ_0054220 Upregulates HMGA1 by the Competitive RNA Pattern to Promote Neural Impairment in MPTP Model of Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disease. Circular RNAs (circRNAs) have been confirmed to regulate neurodegenerative diseases. This study was aimed to explore hsa_circ_0054220 functions in PD. MPP-stimulated SH-SY5Y cells were established as the PD cell model. PD mouse model was established by MPTP. Gene expression in cells and tissues was tested by RT-qPCR. Cell viability and apoptosis were evaluated through CCK-8 and TUNEL assays. The interactions of RNAs were determined by RNA pull-down assay, RIP assay, and luciferase reporter assay. Circ_0054220 expressed at a high level in MPP-treated SH-SY5Y cells. Circ_0054220 inhibition promoted viability and suppressed apoptosis in MPP-stimulated cells. Furthermore, we found that circ_0054220 can competitively bind to miR-145 and miR-625 to upregulate high mobility group A1 (HMGA1) expression. HMGA1 was positively regulated by circ_0054220 and overexpressed in MPP-treated cells as well as the striatum (STR), substantia nigra pars compacta (SNpc), and serum of MPTP-induced mouse model of PD. HMGA1 overexpression counteracted the function of circ_0054220 silencing on cell apoptosis. Furthermore, HMGA1 inhibition notably alleviated motor dysfunction and increased the quantity of neurons in mice resembling PD. Circ_0054220 upregulates HMGA1 by the competitive endogenous RNAs (ceRNA) pattern to promote neural impairment in PD.

Upregulation of miR-29c-3p Hinders Melanoma Progression by Inhibiting CDCA4 Expression.

OBJECTIVE: To investigate the expression and regulation mechanism of miR-29c-3p and cell division cycle associated 4 (CDCA4) in melanoma (MM). Data and Methods. Fifty-nine patients with MM admitted to our hospital were enrolled as the MM group. They were followed up for 3 years to analyze the prognostic factors; meanwhile, 51 healthy subjects were allocated into a normal group. MM cell lines (M21 and C8161) were transfected with miR-29c-3p-mimics, miR-29c-3p-inhibitor, miR-NC, si-CDCA4, and sh-CDCA4. The expression of miR-29c-3p, CDCA4, Bax, Caspase3, Bcl-2, N-cadherin, vimentin, and E-cadherin was quantified, and cell proliferation, migration, invasion, and apoptosis, as well as epithelial-mesenchymal transition (EMT), were determined. RESULTS: Serum miR-29c-3p was lowly expressed and CDCA4 was highly expressed in the MM group. The area under the curve (AUC) of both for diagnosing MM was greater than 0.9. miR-29c-3p and CDCA4 were related to regional lymph node staging (N staging), distant metastasis (M staging), tumor diameter, and pathological differentiation. Low miR-29c-3p and high CDCA4 were associated with poor prognosis of MM. Overexpression of miR-29c-3p and suppression of CDCA4 hindered cell proliferation, migration, invasion, and expression of Bax, Caspase3, N-cadherin, and vimentin, but cell apoptosis and expression of Bcl-2 and E-cadherin were enhanced. Dual-luciferase reporter (DLR) assay confirmed the targeted relationship between miR-29c-3p and CDCA4. After miR-29c-3p-mimics+sh-CDCA4 was transfected into M21 and C8161 cells, the proliferation, invasion, and apoptosis were not different from those in the miR-NC group transfected with unrelated sequences. CONCLUSION: Overexpression of miR-29c-3p suppresses CDCA4 expression and decreases proliferation, migration, invasion, apoptosis, and EMT of MM cells, thus hindering MM progression.

Effect of miR-181a-3p on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting BMP10.

Objective: To explore the regulation relationship between miR-181a-3p and BMP10, and their mechanism of osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (MSCs).Methods: After osteogenic induction of MSCs, the ALP activity was detected by ELISA. The expression of miRNA-181a-3p and BMP10 was detected by RT-qPCR, and the protein levels of BMP10 and osteogenic differentiation marker proteins ALK and RUNX2 were detected by Western blot. The TargetScan online website was used to predict the putative target of miR-181a-3p, and dual luciferase reporter assay was performed to validate the targeting relationship between miR-181a-3p and BMP10.Results: In osteogenic differentiation of MSCs, ALP activity, the level of ALK and RUNX2 was evidently increased (p < .05), and the expression of miR-181a-3p was significantly downregulated (p < .05). Moreover, overexpression of miR-181a-3p obviously decreased the expression of BMP10 (p < .05), miR-181a-3p knockdown increased the expression of BMP10 prominently (p < .05). The transfection of miR-181a-3p mimics resulted in significantly downregulation of ALP activity and RUNX2 protein expression in MSCs (p < .05). In addition, overexpression of BMP10 could reverse the inhibitory effect of miR-181a-3p on osteogenic differentiation (p < .05).Conclusions: In conclusion, we found that miR-181a-3p inhibited osteogenic differentiation of MCSs by targeting BMP10.