Clinical significance of dynamical network indices of surface electromyography for reticular neuromuscular control assessment.

BACKGROUND: There is currently no objective and accurate clinical assessment of reticular neuromuscular control in healthy subjects or patients with upper motor neuron injury. As a result, clinical dysfunctions of neuromuscular control could just be semi-quantified, efficacies and mechanisms of various therapies for neuromuscular control improving are difficult to verify. METHODS: Fourteen healthy participants were required to maintain standing balance in the kinetostatics model of Gusu Constraint Standing Training (GCST). A backward and upward constraint force was applied to their trunk at 0°, 20° and 25°, respectively. The multiplex recurrence network (MRN) was applied to analyze the surface electromyography signals of 16 muscles of bilateral lower limbs during the tests. Different levels of MRN network indices were utilized to assess reticular neuromuscular control. RESULTS: Compared with the 0° test, the MRN indices related to muscle coordination of bilateral lower limbs, of unilateral lower limb and of inter limbs showed significant increase when participants stood in 20° and 25° tests (P < 0.05). The indices related to muscle contribution of gluteal, anterior thigh and calf muscles significantly increased when participants stood in 20° and 25° tests (P < 0.05). CONCLUSIONS: This study applied the dynamical network indices of MRN to analyze the changes of neuromuscular control of lower limbs of healthy participants in the kinetostatics model of GCST. Results showed that the overall coordination of lower limb muscles would be significantly enhanced during performing GCST, partly by the enhancement of neuromuscular control of single lower limb, and partly by the enhancement of joint control across lower limbs. In particular, the muscles in buttocks, anterior thighs and calves played a more important role in the overall coordination, and their involvement was significantly increased. The MRN could provide details of control at the bilateral lower limbs, unilateral lower limb, inter limbs, and single muscle levels, and has the potential to be a new tool for assessing the reticular neuromuscular control. Trial registration ChiCTR2100055090.

A novel regulatory loop miR-101/ANXA2/EGR1 mediates malignant characteristics of liver cancer stem cells.

Increasing evidence suggests that liver cancer stem cells (LCSCs) are the cellular determinants that promote tumor recurrence and metastases. Aberrantly expressed miRNAs were identified in LCSCs and found to play a significant role in modulating biological characteristics of LCSCs. In this study, we implemented miRNA microarrays in CD133+ LCSCs and found miR-101 expression was downregulated. Increasing miR-101 expression repressed the metastasis and tumorigenic potential in LCSCs. Further investigations showed that ANXA2 was a novel target of miR-101. And we revealed that ANXA2 plays a critical role in acceleration of cell cycle and enhancing the migration and invasion abilities of LCSCs. Elevated ANXA2 increased activation of extracellular signal-regulated kinase (ERK) which regulated SOX2 and cell cycle-related kinases. Moreover, ERK phosphorylation inhibited the expression of early growth response 1 (EGR1) which in turn restrained the transcription of miR-101. In vivo experiments, overexpression of miR-101 produced potent inhibitory effects on the growth of LCSCs xenograft tumors as well as ANXA2 knockdown. Taken together, our findings suggest a novel regulatory loop miR-101/ANXA2/EGR1 in LCSCs and may serve as potential therapeutic targets in liver cancer.

miR­302c­3p and miR­520a­3p suppress the proliferation of cervical carcinoma cells by targeting CXCL8.

The aim of the present study was to identify the differentially expressed microRNAs (miRs) in cervical carcinoma (CC) tissues and cells and to explore the function of miR­302c­3p and miR­520a­3p in the proliferation of CC cells. Potential dysregulated miRNAs in CC tissues and tumour­adjacent tissues were detected. Reverse transcription­quantitative PCR (RT­qPCR) was performed to determine the expression of miR­302c­3p, miR­520a­3p and CXCL8 in CC tissues and cell lines. The target genes of the miRNAs were predicted using miRTarBase and verified by luciferase reporter assays. RT­qPCR and western blotting were performed to measure the expression of C­X­C motif ligand (CXCL)8 after transfection. The effect on proliferation was verified by Cell Counting Kit assay and ethynyl­2­deoxyuridine staining. Flow cytometry was utilised to assess the effect on apoptosis. In the present study, miR­302c­3p and miR­520a­3p were markedly downregulated in CC cell lines compared to the normal cervical cell line H8. Functionally, overexpression of miR­302c­3p and/or miR­520a­3p inhibited proliferation and promoted the apoptosis of CC cell lines in vitro, while the knockdown of miR­302c­3p and/or miR­520a­3p had the opposite effect. Furthermore, miR­302c­3p and miR­520a­3p could both bind to CXCL8. Inhibition of CXCL8 in combination with miR­302c­3p and/or miR­520a­3p overexpression exerted proliferation­suppressive and apoptosis­stimulating effects on CC cells, whereas restoring CXCL8 attenuated the miR­302c­3p­ and miR­520a­3p­induced anti­proliferative and pro­apoptotic effects. miR­302c­3p and miR­520a­3p suppress the proliferation of CC cells by downregulating the expression of CXCL8, which may provide a novel target for the treatment of CC.

Hsa_circRNA_102610 upregulation in Crohn's disease promotes transforming growth factor-ß1-induced epithelial-mesenchymal transition via sponging of hsa-miR-130a-3p.

BACKGROUND: The incidence of inflammatory bowel disease, a chronic intestinal inflammatory disorder that includes Crohn's disease (CD) and ulcerative colitis, is rising. Circular RNAs are considered valuable diagnostic biomarkers for CD. Current evidence supports the views that epithelial-mesenchymal transition (EMT) plays an important role in CD pathogenesis, and that hsa-miR-130a-3p can inhibit transforming growth factor-ß1 (TGF-ß1)-induced EMT. Our previous study revealed that hsa_circRNA_102610 was upregulated in CD patients. Moreover, we predicted an interaction between hsa_circRNA_102610 and hsa-miR-130a-3p. Thus, we hypothesized that hsa_circRNA_102610 may play roles in the proliferation and EMT of intestinal epithelial cells by sponging hsa-miR-130a-3p to participate in the pathogenesis of CD. AIM: To explore the mechanism of hsa_circRNA_102610 in the pathogenesis of CD. METHODS: The relative expression levels of hsa_circRNA_102610 and hsa-miR-130a-3p in patients were detected by quantitative reverse transcription-polymerase chain reaction. The proliferation of human intestinal epithelial cells (HIECs) and normal-derived colon mucosa cell line 460 (NCM460) cells was detected by cell counting kit-8, 5-ethynyl-2'-deoxyuridine staining and cell cycle assays following overexpression or downregulation of hsa_circRNA_102610. Cell proliferation assays were performed as described above in a rescue experiment with hsa-miR-130a-3p mimics. The interaction of hsa_circRNA_102610 and hsa-miR-130a-3p was verified by fluorescence in situ hybridization and dual luciferase reporter assays. The relative expression levels of CyclinD1, mothers against decapentaplegic homolog 4 (SMAD4), E-cadherin, N-cadherin and Vimentin were detected by western blotting following hsa_circRNA_102610 overexpression, TGF-ß1-induced EMT or hsa-miR-130a-3p mimic transfection (in rescue experiments). RESULTS: Upregulation of hsa_circRNA_102610 was determined to be positively correlated with elevated fecal calprotectin levels in CD (r = 0.359, P = 0.007) by Pearson correlation analysis. Hsa_circRNA_102610 promoted the proliferation of HIECs and NCM460 cells, while hsa-miR-130a-3p reversed the cell proliferation-promoting effects of hsa_circRNA_102610. Fluorescence in situ hybridization and dual luciferase reporter assays showed that hsa_circRNA_102610 directly bound hsa-miR-130a-3p in NCM460 and 293T cells. An inverse correlation between downregulation of hsa-miR-130a-3p and upregulation of hsa_circRNA_102610 in CD patients was observed (r = -0.290, P = 0.024) by Pearson correlation analysis. Moreover, overexpression of hsa_circRNA_102610 promoted SMAD4 and CyclinD1 protein expression validated by western-blotting. Furthermore, over-expression of hsa_circRNA_102610 promoted TGF-ß1 induced EMT in HIECs and NCM460 cells via targeting of hsa-miR-130a-3p, with increased expression of Vimentin and N-cadherin and decreased expression of E-cadherin. CONCLUSION: Hsa_circRNA_102610 upregulation in CD patients could promote the proliferation and EMT of intestinal epithelial cells via sponging of hsa-miR-130a-3p.