miR-384-5p regulates inflammation in Candida albicans-induced acute lung injury by downregulating PGC1ß and enhancing the activation of Candida albicans-triggered signaling pathways.

Acute lung injury (ALI) is one of the most prevalent respiratory syndromes of excessive inflammatory reaction during lung infection. Candida albicans (C. albicans) infection is among the leading causes of ALI. MicroRNAs (miRNAs) regulate the expression of target mRNAs, including those involved in inflammatory processes, by binding to the 3'UTR. To date, the roles of miRNAs in C. albicans-induced ALI remain unclear. In this study, we investigated the role of miR-384-5p in C. albicans-induced ALI and its underlying molecular mechanism. RT-PCR, Western blot, ELISA, Myeloperoxidase (MPO) assay, microRNA target analysis, transient transfection, and luciferase reporter assay were utilized. In vivo study was conducted on mouse model. The expression of miR-384-5p was upregulated and positively correlated with inflammatory cytokine production in lung tissues and RAW264.7 and J774A.1 macrophages infected with C. albicans. The miR-384-5p inhibitor alleviated the inflammatory reaction induced by C. albicans. Target prediction analysis revealed that PGC1ß was a target of miR-384-5p, which was further validated by the PGC1ß 3'-UTR luciferase assay and the inverse correlation between the expression of miR-384-5p and PGC1ß in C. albicans-infected ALI tissues and macrophages. Moreover, macrophages transfected with miR-384-5p mimic exhibited reduced levels of PGC1ß. The suppression of the expression of PGC1ß by C. albicans infection in the macrophages was abrogated by miR-384-5p inhibitor. Then, we demonstrated that PGC1ß played an inhibitory role in C. albicans-induced production of inflammatory cytokines. Furthermore, suppression of miR-384-5p in macrophages inhibited the activation of the NF-κB, MAPK, and Akt signaling pathways triggered by C. albicans, but not the STAT3 pathway. These results demonstrate that miR-384-5p contributes to C. albicans-induced ALI at least in part by targeting PGC1ß and enhancing the activation of the NF-κB, MAPK, and Akt inflammatory signaling pathways. Thus, targeting miR-384-5p might exert a protective effect on C. albicans-induced ALI.

miR-4698-Trim59 axis plays a suppressive role in hepatocellular carcinoma.

microRNAs (miRNAs) are important players in tumor suppression and oncogenesis. In this study, we aimed to explore the role of miR-4698 with its potential target tripartite motif-containing 59 (Trim59), a protein with oncogenic function, in hepatocellular carcinoma (HCC). The expression of miR-4698 was significantly lower in HCC tissues and HCC cell lines compared to normal tissues adjacent to tumors and in normal hepatic cell lines. Overexpression of miR-4698 in HCC cells by transfection of its mimic significantly inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), whereas its antisense oligonucleotides (ASOs) exerted the opposite effect. Trim59 was identified as a target of miR-4698 in miRDB, and consistent with this prediction, the expression of Trim59 was inversely correlated with that of miR-4698 in HCC, and miR-4698 overexpression led to a significant decrease in the luciferase activity of pRL-Trim59-3'-UTR but not mutant pRL-Trim59-3'-UTR. Moreover, the miR-4698 mimic inhibited the expression of Trim59. Overexpression of Trim59 abrogated the inhibitory effects of miR-4698. In conclusion, these data show that the miR-4698-Trim59 axis plays a tumor-suppressive role in HCC.

Unusual findings of acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2): A multicenter study.

INTRODUCTION: AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2) [inv(3)/t(3;3)] was very rare. Currently, most reports of AML-inv(3)/t(3;3) were from Western countries, and few reports were from Asian countries. Racial differences in patients with AML-inv(3)/t(3;3) are still unknown. METHODS: Between January 1996 and April 2018, a total of 37 AML cases with inv(3)/t(3;3) were studied retrospectively. They were collected from 2229 primary AML cases performed with conventional cytogenetic analysis (37/2229, 1.66%). RESULTS: Here, some differences were found by comparing our data with those from Western countries. In our series, AML with inv(3)(q21q26) had a lower incidence than that with t(3;3)(q21;q26) (11 vs 26 cases). Our patients seemed to be more younger (median, 43 years) and have lower hemoglobin concentrations (median, 73 g/L) and higher platelet count (median, 351 × 109 /L). A higher incidence of acute monoblastic and monocytic leukemia (45.9%) was observed in our patients. Immunophenotypic studies showed that CD38 (30.8%) was not so frequently expressed as that in the earlier reports. Mutations analysis showed a high frequency of NRAS mutations (45.0%), followed by SF3B1(15.0%), GATA2(15.0%), FLT3-ITD(10.0%), C-Kit/D816(5.0%), and CEBPA(5.0%), without mutation of NPM1(Exon12)or JAK2V617. CONCLUSION: Ethnic differences do exist between the Chinese and Western patients with AML-inv(3)/t(3;3), and more attention should be paid involving different ethnic populations and geographic regions.

Upregulation of long noncoding RNA TUG1 by EGR1 promotes adenomyotic epithelial cell migration and invasion through recruiting EZH2 and suppressing TIMP2.

Emerging studies showed that lncRNA taurine upregulated 1 (TUG1) plays important roles in diverse biological processes. However, there is no previously published research reporting the regulatory role of lncRNAs in the progression of adenomyosis. In the present study, we found that TUG1 is upregulated in human adenomyosis, and the overexpression of TUG1 is associated with the transcription factor early growth response 1 (EGR1). Functionally, the knockdown of TUG1 inhibited adenomyotic epithelial cell migration and invasion but not growth. The mechanistic experiments demonstrated that the function of TUG1 in adenomyotic epithelial cell invasion is, at least in part, through recruiting the enhancer of zeste homolog 2 (EZH2) to the promoter of tissue inhibitor of metalloproteinases 2 (TIMP2) and negatively regulating its expression. Our study demonstrated that TUG1 promotes the migration and invasion of human adenomyotic epithelial cells, and EGR1/TUG1/EZH2/TIMP2 may be a potential therapeutic target for adenomyosis.

Inhibition of Phospholipase D1 mRNA Expression Slows Down the Proliferation Rate of Prostate Cancer Cells That Have Transited to Androgen Independence.

To explore the role of phospholipase D1 (PLD1) mRNA in transition of prostate cancer (PCa) cells to androgen independence, we used Arraystar Human LncRNA Microarray V3.0 to detect and compare the differential expression of PLD1 and its signaling pathway-related gene in standard androgen dependence prostate cancer (ADPC) cell line LNCaP before and after the occurrence of androgen independence prostate cancer (AIPC) transition. In addition, we used the shRNA lentiviral vector to inhibit the PLD1 mRNA expression and observed its effect on LNCaP cell proliferation after AIPC transition by using MTS method. The results showed that the expression level of PLD1 mRNA was increased by 373-fold after AIPC transition (P<0.05); the PI3K/AKT signaling pathway-related gene expression was also elevated (P<0.05); the growth rate of LNCaP cells that had transited to androgen independence was reduced by about 30% when the PLD1 mRNA expression was inhibited by the shRNA lentivirus as compared with the negative control group (P<0.05). All these results suggest that PLD1 mRNA and the related PI3K/AKT signaling pathway may play an important role in AIPC. Down-regulating the expression of PLD1 mRNA could to some extent inhibit the proliferation rate of PCa cells after AIPC transition.

Clinical value of integrated-signature miRNAs in colorectal cancer: miRNA expression profiling analysis and experimental validation.

MicroRNA (miRNA) expression profiling of colorectal cancer (CRC) are often inconsistent among different studies. To determine candidate miRNA biomarkers for CRC, we performed an integrative analysis of miRNA expression profiling compared CRC tissues and paired neighboring noncancerous colorectal tissues. Using robust rank aggregation method, we identified a miRNA set of 10 integrated-signature miRNAs. In addition, the qRT-PCR validation demonstrated that 9 miRNAs were consistent dysregulated with the integrative analysis in CRC tissues, 4 miRNAs (miR-21-5p, miR-183-5p, miR-17-5p and miR-20a-5p) were up-regulated expression, and 5 miRNAs (miR-145-5p, miR-195-5p, miR-139-5p, miR-378a-5p and miR-143-3p) were down-regulated expression (all p < 0.05). Consistent with the initial analysis, 7 miRNAs were found to be significantly dysregulated in CRC tissues in TCGA data base, 4 miRNAs (miR-21-5p, miR-183-5p, miR-17-5p and miR-20a-5p) were significantly up-regulated expression, and 3 miRNAs (miR-145-5p, miR-139-5p and miR-378a-5p) were significantly down-regulated expression in CRC tissues (all p < 0.001). Furthermore, miR-17-5p (p = 0.011) and miR-20a-5p (p = 0.003) were up-regulated expression in the III/IV tumor stage, miR-145-5p (p = 0.028) and miR-195-5p (p = 0.001) were significantly increased expression with microscopic vascular invasion in CRC tissues, miR-17-5p (p = 0.037) and miR-145-5p (p = 0.023) were significantly increased expression with lymphovascular invasion. Moreover, Cox regression analysis of CRC patients in TCGA data base showed miR-20a-5p was correlated with survival (hazard ratio: 1.875, 95%CI: 1.088-3.232, p = 0.024). Hence, the finding of current study provides a basic implication of these miRNAs for further clinical application in CRC.