Objective To summarize the mechanism of microRNA in the recurrence and metastasis of hepatocellular carcinoma (HCC) and its possible clinical application. Methods The relevant literatures at home and abroad were reviewed to summarize the results of various scholars. Results microRNA played an important role in cell proliferation and apoptosis of HCC. microRNA of different types promoted or inhibited the recurrence and metastasis of HCC through different action targets and molecular pathways. Conclusions microRNA has a regulation role in the recurrence and metastasis of HCC, and the depth mechanisms study of microRNA in the recurrence and metastasis of HCC provides great significance to clinical therapy. The miRNA is expected to be one of the new target on the prediction and treatment of recurrence and metastasis in HCC.
ObjectiveTo summarize the research progress of microRNA-200 (miR-200) family in triple-negative breast cancer (TNBC).MethodsRelevant literatures at home and abroad were systematically retrieved and read to review the research progress of miR-200 family in TNBC in recent years.ResultsThe miR-200 family played an important role in the proliferation, invasion, and metastasis of TNBC, as well as the resistance to treatment. It could also be used as potential therapeutic targets and biological predictors. Different miR-200 family members and differential expression mediated various targeting effects, which may be related to differences in signaling pathways and cellular environment.ConclusionsmiR-200 family plays a key regulatory role in the occurrence and development of TNBC, and it is expected to provide new ideas for the treatment and prognosis evaluation of TNBC. However, its mechanism of action still needs further study.
ObjectiveTo investigate the function and possible mechanism of microRNA-199b-5p (miR-199b-5p) in Ewing's sarcoma cell lines so as to provide theoretical basis for biological treatment in the future. MethodsA673 cells and TC252 cells were adopted as Ewing's sarcoma cell lines in vitro. miR-199b-5p oligonucleotide fragments (mimic) and scramble control (mimic control) were used to transfect TC252 cells and A673 cells, respectively. The expression of miR-199b-5p was measured in 2 cell lines by real-time quantitative-PCR and compared with that in mesenchymal stem cells (MSCs). The cell proliferation was examined by cell counting kit 8. The cell cycle and apoptosis were detected by flow cytometry. The possible targets of miR-199b-5p were determined by luciferase assays. The protein expressions of possible targets were measured by Western blot. ResultsThe expression of miR-199b-5p in control group was significantly down-regulated in A673 cells and TC252 cells when compared with that in MSCs (P<0.05); and the expression of miR-199b-5p in experimental group was significantly up-regulated when compared with that in control group (P<0.05). G1 phase cells increased obviously and S phase cells decreased significantly compared with corresponding cells in control group (P<0.05); but no significant difference was found in G2/M phase cells between 2 groups (P>0.05). The apoptosis rate increased significantly in experimental group when compared with that in control group (P<0.05). The possible targets of miR-199b-5p were cyclin-L1 (CCNL1) and c-Kit by luciferase assays. Western blot results showed that the CCNL1 and c-Kit protein expression levels in experimental group were significantly lower than those in control group (P<0.05). ConclusionmiR-199b-5p can suppress the cell proliferation, block the cell cycle, and promote the cell apoptosis, so miR-199b-5p inhibits Ewing's sarcoma cell lines by targeting CCNL1 and c-Kit.
ObjectiveTo summarize the current research progress of serum exosome microRNAs in patients with colorectal cancer.MethodsThe domestic and foreign literatures related to serum exosome microRNAs of colorectal cancer patients, which had been reported in recent years were collected through literature search. Subsequently, those literatures were used to read and review.ResultsExosomes were extracellular vesicles, which contained lipids, proteins, DNA, RNA (mRNA, microRNA, and long non-coding RNA), and other molecules. These vesicles mediated communication between cells by transporting the above molecules. Exosomes in serum were the main carriers of microRNAs in the blood circulation system. Serum exosome microRNAs could affect the proliferation, invasion, and metastasis of colorectal cancer cells, mediate the drug resistance of colorectal cancer cells, and could be used as biomarkers to predict the prognosis of colorectal cancer.ConclusionsSerum exosome microRNAs play important role in the occurrence, development, treatment, and diagnosis of colorectal cancer. As a class of biomarker, serum exosome microRNAs have great potential in the early diagnosis and prognostic evaluation of colorectal cancer.
Objectives To evaluate the expression levels of serum microRNA-21 (miRNA-21) and microRNA-155 (miRNA-155) from patients and rats with pancreatic cancer, and to explore its value in the diagnosis of pancreatic cancer. Methods The clinical materials and the serum samples from 18 patients with pancreatic cancer (pancreatic cancer group) and 12 patients with benign pancreatic disease (benign pancreatic disease group) admitted to Fujian Medical University Union Hospital between January 2016 and December 2016 were collected prospectively. The real-time fluorescent quantitative PCR was performed to detect the levels of serum miRNA-21 and miRNA-155. 7, 12-dimethylbenz (a) anthracene (DMBA)-induced pancreatic cancer rat models (n=20) and the models of the blank control group (sham operation, n=10) were established and the serum samples from the pancreatic cancer group and the blank control group were measured by the real-time fluorescent quantitative PCR, to detect the levels of miRNA-21 and miRNA-155. Results The median expression levels of serum miRNA-21 and miRNA-155 were 1.99 (1.43–5.30) and 7.06 (4.98–21.48) in the pancreatic cancer group, as well as 1.28 (0.58–2.01) and 2.20 (1.76–3.02) in the benign pancreatic disease group. The expression levels of serum miRNA-21 and miRNA-155 were significantly higher in the pancreatic cancer group (Z=–2.621,P=0.009; Z=–3.430,P=0.001). In animal studies, the rat models of pancreatic cancer were successfully established and 11 rats with pancreatic cancer were acquired, as well as 9 rats in the blank control group were acquired. The median expression levels of serum miRNA-21 and miRNA-155 were 2.12 (1.33–2.72) and 16.45 (7.18–25.40) in the rat pancreatic cancer group, as well as 1.00 (0.45–1.60) and 1.49 (1.25–1.97) in the blank control group. The expression levels of serum miRNA-21 and miRNA-155 were significantly higher in the rat pancreatic cancer group (Z=–2.621,P=0.009; Z=–3.609,P<0.001). For distinguishing pancreatic cancer from benign diseases, the best cutoff value of serum miRNA-21 level was 4.21 and the sensitivity and specificity were 75.0% and 61.1% respectively; the best cutoff value of serum miRNA-155 level was 4.67 and the sensitivity and specificity both were 83.3%. Conclusions The serum miRNA-21and miRNA-155 levels are elevated both in patients and rats with pancreatic cancer. Detection of serum miRNA-155 will be helpful to some extent to distinguish pancreatic cancer from benign diseases.
Objective To explore the effects of dioscin (Dio) on airway inflammation and microRNA-155 (miR-155)/cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathways in asthmatic mice. Methods Seventy mice were randomly divided into control group, model group, inhibitor negative control group (inhibitor-NC group), miR-155 inhibitor group, and Dio group, Dio+miR-155 mimic negative control group (Dio+mimic-NC group), Dio+miR-155 mimic group, with 10 mice in each group. Using house dust mite to induce the preparation of asthma mouse models; enzyme linked immunosorbent assay was used to detect the levels of PGE2, tumor necrosis factor α (TNF-α), cysteyl leukotrienes (CysLTs), cysteyl leukotriene receptor 1 (CysLTR1) and interleukin (IL)-4, IL-5, IL-13 in mouse bronchoalveolar lavage fluid (BALF); hematoxylin-eosin and periodic acid-Schiff staining were used to observe the infiltration of inflammatory cells around the airway and the secretion of mucus by goblet cells; quantitative real-time PCR was used to detect the expression levels of miR-155 and COX-2 mRNA in mouse lung tissue; Western blot was used detect the expression of COX-2 protein in mouse lung tissue. Results MiR-155 inhibitor and Dio could reduce the levels of PGE2, TNF-α, CysLTs, CysLTR1 and IL-4, IL-5, IL-13 in BALF of asthmatic mice, reduce lung tissue inflammatory cell infiltration and goblet cell mucus secretion, and reduce lung tissue miR-155, COX-2 mRNA and protein expression; and miR-155 mimic could significantly weaken the anti-asthma effect of Dio. Conclusion The anti-asthma effect of Dio may be related to the inhibition of miR-155/COX-2/PGE2 pathway to reduce airway inflammation in asthmatic mice.
Objective To construct human recombinant lentiviral expression vector of microRNA-210 (miR-210)and to explore the over-expression of miR-210 on the capillary formation in human umbilical vein endothelial cells 12 (HUVE-12). Methods The recombinant lentiviral expression vector of pGCSIL-green fluorescent protein (GFP)-pre-miR-210 wasconstructed by molecular cloning and transfected to HUVE-12 (LV-miR-210-GFP group), only pGCSIL-GFP was transfectedas control group (LV-GFP group). The miR-210 expression activity was evaluated by GFP reporter through fluorescencedetection and real-time fluorescent quantitative PCR. The ephrinA3 protein expression was measured by flow cytometry. Theconcentration of vascular endothelial growth factor (VEGF) in culture supernatant was determined by ELISA. The cells werecultured in 96-well culture plate coated with Matrigel to assess the abil ity of capillary formation. Results The recombinantplasmid pGCSIL-GFP-pre-miR-210 was confirmed by restriction endonuclease analysis and DNA sequencing. Fluorescencedetection showed that the fluorescence intensity of GFP was highest between 48 and 72 hours after transfection. Real-timefluorescent quantitative PCR showed that the miR-210 expression of LV-miR-210-GFP group was 9.72 times higher than thatin LV-GFP group (t= —11.10，P=0.00). Flow cytometry analysis showed that the positive cell rate of enphrinA3 in LV-miR-210-GFP group (12.52% ± 0.67%) was significantly lower than that in LV-GFP group (73.22% ± 1.45%) (t= —66.12，P=0.00).The concentration of VEGF in supernatant in LV-miR-210-GFP group was significantly higher than that in LV-GFP group[(305.29 ± 16.52) pg/mL vs. (42.52 ± 3.11) pg/mL, t= —27.06，P=0.00]. In vitro capillary-l ike formation assay showed that thenumber of capillaries was significantly larger in LV-miR-210-GFP group than in LV-GFP group (17.33 ± 6.33 vs. 6.33 ± 2.33,t= —2.83，P=0.04). Conclusion The recombinant lentiviral expression vector of miR-210 is constructed successfully andHUVE-12 over-expressing miR-210 can significantly increase the capillary formation, which facil itates further study on themolecular functions of miR-210 in angiogenesis.
Objective To determine the expression levels of micro RNA (miR)-196, miR-217, and transforming growth factor β receptor 1 (TGFβR1) protein in the pancreatic ductal adenocarcinoma tissues and its adjacent tissues, to reveal the relationship among them in the pathological process of pancreatic ductal adenocarcinoma. Methods A total of 30 cases’ pancreatic ductal adenocarcinoma tissues and its adjacent tissues were collected. The expression levels of miR-196b and miR-217 in the pancreatic ductal adenocarcinoma and adjacent tissues were detected by real-time fluorescence quantitative polymerase chain reaction method, the level of TGFβR1 protein was detected by Western blotting method. Results In the pancreatic ductal adenocarcinoma tissues, the expression levels of miR-196b and TGFβR1 protein were significantly higher than those of adjacent tissues (P<0.001), while the level of miR-217 was significantly lower than that of adjacent tissues (P=0.001). For further detection, the level of miR-196b in pancreatic ductal adenocarcinoma tissues was significantly positively correlated with the expression level of TGFβR1 protein (r=0.803, P<0.001), while the expression level of miR-217 was negatively correlated with the expression level of TGFβR1 protein (r=–0.839, P<0.001). Conclusions Expression TGFβR1 protein in pancreatic ductal adenocarcinoma tissues may be bi-directionally regulated by miR-196b and miR-217. This two-way regulating mechanism may be one of the important mechanisms for restricting the development of pancreatic ductal adenocarcinoma, implying a potential target for treatment of pancreatic cancer.
Hematopoietic stem cells (HSCs) are tissue specific stem cells that replenish all mature blood lineages during the lifetime of an individual. Hematopoietic cell clusters in the aorta of vertebrate embryos play a pivotal role in the formation of the adult blood system. Recently, people have learned a lot about the embryonic HSCs on their development and homing. During their differentiation, HSCs are regulated by the transcription factors, such as Runx1 and Notch signaling pathway, etc. MicroRNAs also regulate the self-renewal and differentiation of hematopoietic stem/progenitor cells on the post-transcriptional levels. Since the onset of circulation, the formation of HSCs and their differentiation into blood cells, especially red blood cells, are regulated by the hemodynamic forces. It would be of great significance if we could treat hematologic diseases with induced HSCs in vitro on the basis of fully understanding of hemotopoietic stem cell development. This review is focused on the advances in the research of HSCs' development and regulation.
ObjectiveTo summarize the regulating mechanism of microRNA in tumor microenvironment. MethodThe literatures about the studies on the mechanism regulated by microRNA for tumor microenvironment were reviewed according to the results searched from PubMed in recent years. ResultsmicroRNA might be participated in regulation of tumor microenvironment factors such as hypoxia-inducible factor, tumor associated fibroblasts, extracellular matrix, which leaded to a change in biological behavior of tumor cells by reforming the microenviroment. ConclusionsmicroRNA has been participated in regulating many factors of tumor microenvironment. The change of neoplastic microenvironment has been recognized to play a critical role in the development of cancer. Therefore revealing microRNA mechanism for tumor microenvironment could not only help exploring the biological behavior of tumor cells, but also come an important insight for new means of diagnosis and treatment of cancer.