lncRNA MCM3AP-AS1 inhibits the progression of colorectal cancer via the miR-19a-3p/FOXF2 axis.

BACKGROUND: Long non-coding RNA MCM3AP antisense RNA 1 (lncRNA MCM3AP-AS1) has a regulatory role in the development of diverse malignancies, whereas its role and mechanism in colorectal cancer (CRC) is not yet clear. METHODS: The relative expression of MCM3AP-AS1, miR-19a-3p and forkhead box F2 (FOXF2) mRNA in 53 cases of CRC and its adjacent normal tissues, human normal colonic mucosal cells (FHC cells) and CRC cell lines was examined by a quantitative real-time polymerase chain reaction, and the changes of cell multiplication and migration were examined by the cell counting kit-8 method, EdU test, and scratch-healing test, respectively. Bioinformatics, dual-luciferase reporter gene assay and a RNA immunoprecipitation experiment were adopted to predict and verify the relationship between MCM3AP-AS1 and miR-19a-3p; bioinformatics and dual-luciferase reporter gene assay were adopted to predict and verify the relationship between miR-19a-3p and FOXF2. Western blotting was executed to examine the effects of MCM3AP-AS1 overexpression or knockdown on FOXF2 protein expression. RESULTS: MCM3AP-AS1 expression was down-modulated in CRC, and its dysregulation was linked to unfavorable pathological characteristics. MCM3AP-AS1 significantly impeded the multiplication and migration of CRC cells. MCM3AP-AS1 was recognized as a molecular sponge to suppress miR-19a-3p expression, and FOXF2 was a target gene of miR-19a-3p. MCM3AP-AS1 positively modulated FOXF2 expression, and its biological effect was dependent the on miR-19a-3p/FOXF2 axis. CONCLUSIONS: MCM3AP-AS1 can inhibit CRC promoting by modulating the miR-19a-3p/FOXF2 axis.

The impact of cardiomotor rehabilitation on endothelial function in elderly patients with chronic heart failure.

BACKGROUND: To explore the effects of cardiac exercise rehabilitation on peripheral blood endothelial progenitor cells (EPC) in elderly patients with chronic heart failure. METHODS: 80 elderly patients with chronic heart failure were selected from March 2017 to March 2019 and randomly divided into two groups (N = 40). The control group was treated routinely and walked freely for 30-60 min every day. The patients in the exercise rehabilitation group developed a cardiac exercise rehabilitation plan. Then, cardiac function and peripheral blood B-natriuretic peptide (BNP) levels in the two groups were compared. The cell viability, proliferation, apoptosis, and invasion ability of EPCs were detected. The levels of the PI3K/AKT pathway and eNOS and VEGF were compared. RESULTS: There were no significant differences in all indexes between the two groups before treatment (P > 0.05), and both improved significantly after treatment (P < 0.05). After treatment, LVEF and LVFS in the exercise rehabilitation group were significantly higher than those in the control group (P < 0.05), and LVEDD and LVESD were significantly lower than those in the control group (P < 0.05). The BNP level in the exercise rehabilitation group was significantly lower than that in the control group (P < 0.05). The cell viability, proliferation, invasion ability of EPC, and the levels of PI3K, AKT, eNOS, and VEGF mRNA and protein in the exercise rehabilitation group were significantly higher than those in the control group. Apoptosis rate was significantly lower than those in the control group (P < 0.05). CONCLUSIONS: Visceral exercise rehabilitation can improve cardiac ejection and myocardial function in elderly patients with chronic heart failure, and can promote the vitality, proliferation, and invasion of peripheral blood EPC, and promote the expression of eNOS and VEGF by upregulating the PI3K/AKT pathway to promote angiogenesis and endothelial function.

LncRNA FUNDC2P4 down-regulation promotes epithelial-mesenchymal transition by reducing E-cadherin expression in residual hepatocellular carcinoma after insufficient radiofrequency ablation.

PURPOSE: Hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA) could induce epithelial-mesenchymal transition (EMT) in residual tumours, resulting in rapid and aggressive recurrence. However, the role of EMT-related Long noncoding RNAs (lncRNAs) in residual tumour progression remains unclear. METHODS: Insufficient RFA was simulated in vitro by heating Huh7 cells in water bath at 47 °C, named as Huh7-H. Cell invasion, migration assays and wound healing assay were conducted for functional analysis. Cell proliferation was determined by CCK8 assay. Differential expression profile of EMT-related lncRNAs between Huh7-H and Huh7 was analysed by LncPath human EMT array, and validated by qRT-PCR. Gain/loss-of-function assays of selected lncRNA were conducted by over-expressing or silencing its expression. RESULTS: Huh7-H presented characteristic EMT morphological changes. WB analysis showed significantly decreased E-cadherin in Huh7-H cells. Transwell assays indicated the abilities of Huh7-H cells in migration and invasion were evidently strengthened. A new lncRNA, FUNDC2P4, was identified by LncPath human EMT array to be significantly down-regulated in Huh7-H cells. In vitro studies showed overexpression of FUNDC2P4 inhibited proliferation, invasion and migration potential and up-regulated E-cadherin expression in SMMC-7721 cells, whereas silencing FUNDC2P4 promoted these potentials and down-regulated E-cadherin expression in Huh7 cells. CONCLUSIONS: We explored that lncRNA FUNDC2P4 down-regulation promoted EMT leading to tumour proliferation, invasion and migration by reducing E-cadherin expression in residual HCC after insufficient RFA in vitro. These results suggest that FUNDC2P4 may have potentially therapeutic value for prevention and treatment of HCC recurrence after RFA in the future.

Epithelial-mesenchymal transition-related gene prognostic index and phenotyping clusters for hepatocellular carcinoma patients.

Epithelial-mesenchymal transition (EMT) contributes to high tumor heterogeneity and the immunosuppressive environment of the HCC tumor microenvironment (TME). Here, we developed EMT-related genes phenotyping clusters and systematically evaluated their impact on HCC prognosis, the TME, and drug efficacy prediction. We identified HCC specific EMT-related genes using weighted gene co-expression network analysis (WGCNA). An EMT-related genes prognostic index (EMT-RGPI) capable of effectively predicting HCC prognosis was then constructed. Consensus clustering of 12 HCC specific EMT-related hub genes uncovered two molecular clusters C1 and C2. Cluster C2 preferentially associated with unfavorable prognosis, higher stemness index (mRNAsi) value, elevated immune checkpoint expression, and immune cell infiltration. The TGF-ß signaling, EMT, glycolysis, Wnt ß-catenin signaling, and angiogenesis were markedly enriched in cluster C2. Moreover, cluster C2 exhibited higher TP53 and RB1 mutation rates. The TME subtypes and tumor immune dysfunction and exclusion (TIDE) score showed that cluster C1 patients responded well to immune checkpoint inhibitors (ICIs). Half-maximal inhibitory concentration (IC50) revealed that cluster C2 patients were more sensitive to chemotherapeutic and antiangiogenic agents. These findings may guide risk stratification and precision therapy for HCC patients.

Lipid Coated and Chlorin e6 Loaded Calcium Carbonate for Effective In Situ Immunotheraphy of Colorectal Cancer.

Cancer vaccine is well recognized as a novel but effective way for cancer immunotherapy. Especially, the role of dendritic cells (DCs) in antigen presentation properties is critical for the final performance of cancer vaccine. Herein, a lipid (Li) coated calcium carbonate (CC) vehicle (Li/CC) was employed to load chlorin e6 (Ce6) to serve as a potential in situ vaccine (Li/CC-Ce6) for effective immunotherapy of colorectal cancer. It was suggested that the loaded Ce6 within Li/CCCe6 can be activated under laser irradiation. The photodynamic therapy (PDT) of Ce6 was expected to produce reactive oxygen species (ROS) to cause cell death and expose tumor-associated antigen (TAA). In addition, the produced ROS can mimic the inflammatory responses for the recruitment of DC to initiate strong immune response cascade. Moreover, the recruitment of DC can recognize the exposed TAA to stimulate DC for effective vaccination in situ. Results from in vitro and in vivo assays demonstrated the strong ability of this platform to enhance DC vaccination, resulting in promising growth inhibition of both primary and distant tumors.

Bioinformatical Analysis of Gene Expression Omnibus Database Associates TAF7/CCNB1, TAF7/CCNA2, and GTF2E2/CDC20 Pathways with Glioblastoma Development and Prognosis.

OBJECTIVE: This study bioinformatically analyzed aberrant genes and pathways for associations with glioblastoma development and prognosis. METHODS: The Gene Expression Omnibus (GEO) database was searched and 4 GEO datasets (GSE4290, GSE50161, GSE116520, and GSE90598) were retrieved for limma and RobustRankAggreg package analyses of differentially expressed genes (DEGs) between glioblastoma and normal brain tissues. Functional enrichment analysis was conducted for the main biological functions of these DEGs, whereas the hub genes were identified using the protein-protein interaction network and confirmed for transcriptional and translational levels using the Cancer Genome Atlas, the Genotype-Tissue Expression, and the Human Protein Atlas data. The prognostic values of these hub genes were analyzed using the Chinese Glioma Genome Atlas. Their transcriptional factor regulation network was constructed to assess the roles in glioblastoma development and progression. RESULTS: A total of 473 DEGs (182 upregulated and 291 downregulated) were identified and the hub genes (including CCNB1, CDC20, CCNB2, BUB1, and CCNA2) were shown in module 1 and enriched in the cell cycle or p53 signaling pathway. The highly expressed CCNB1, CDC20, BUB1, and CCNA2 in patients with glioblastoma were associated with poor overall survival, whereas TAF7 could upregulate expression of CCNB1 and CCNA2 and GTF2E2 could upregulate CDC20 expression in glioblastoma. CONCLUSIONS: This study showed several DEGs in glioblastoma, and aberrant expression of their hub genes was associated with glioblastoma pathogenesis and poor prognosis, especially the signaling axes of TAF7/CCNB1, TAF7/CCNA2, and GTF2E2/CDC20.

[Effect of yizhi jiannao granule on the behavior and neuron apoptosis in SAMP/8 mice].

OBJECTIVE: To investigate the effect of yizhi jiannao granule concentration fluid (YCF) on the behavior, the apoptosis rate of hippocampus neuron and the expression of apoptosis gene Bcl-2, Bax in senescence accelerated mice Senile-Prone/8 (SAMP/8), and to discuss some mechanism of traditional chinese medicine YCF in improving the capability of learning and memory. METHODS: Forty 6-month old SAMP/8 mice were randomly divided into the old group, huperzine A (Hup-A) group and YCF group. Ten 4-month old SAMP/8 mice were served as a young control group. Four groups were given different drugs for 8 weeks, their behavior changes were observed, and the hippocampus were taken out to examine the apotosis rate by flow cytomeutry (FCM) and the expression of Bcl-2, Bax mRNA by RT-PCR. RESULTS: In the YCF group, the escape latency was significantly shortened, the time of swim in the platform quadrant significantly increased, the apoptosis rate of hippocampus neural decreased; the level of Bcl-2 mRNA and the rate of Bcl-2/Bax increased, and the level of Bax mRNA decreased. CONCLUSION: Yizhi jiannao granule can decrease the neuron apoptosis rate and the Bax level, increase the Bcl-2 level, and modulate the rate of Bcl-2/Bax in SAMP/8 brain, which is probably part of the mechanisms of inhibiting the apoptosis and improving learning and memory.