AbstractAimsThe underlying mechanism and constitution of spontaneous abortions are complicated and heterogeneous. Many factors, including epigenetic scenarios like micro‐ribonucleic acids (miRNAs, MIRs), can additively affect the progression of pregnancy losses. This study aimed to evaluate whether the expression levels of placental inhibitor and/or activator miRNAs had a difference between the numerically abnormal and normal karyotyped spontaneous abortions.MethodsThe case–control study included 100 spontaneous abortion materials consisting of trophoblastic tissues with 42 disomies (controls), 43 aneuploidies (including trisomy 16, 21, 22, and monosomy X), and 15 triploidies. Disomic abortion materials with XX normal karyotypes were omitted from the study to exclude possible maternal decidual cell contamination. Total RNA isolation was performed with TRIzol™ reagent directly from frozen trophoblastic tissues, and the mature miRNAs were obtained by reverse transcription via quantitative real‐time polymerase chain reaction (qRT‐PCR). Then, the expression levels of placental activators MIR378a‐5p, MIR376c, MIR195, and inhibitors MIR34a and MIR210 were relatively evaluated using MIR130 as a reference.ResultsThe expression level of placental inhibitor MIR34a was detected to be high in trisomic abortion materials (trisomy 16 and 21) when compared to the disomic ones (p = 0.0324). MIR195 (p = 0.0484) and MIR34a (p = 0.0346) expression levels were increased in numerically abnormal cases with advanced maternal age compared to the disomic ones within all maternal ages.ConclusionsIt seems likely that the high expression level of MIR34a and the coexistence of trisomic abortion materials are quite interrelated with the additive effect of advanced maternal age.

2020-04-01·Biomedicine & Pharmacotherapy2区 · 医学

MiR-195 regulates CD40 to maintain Th17/Treg balance in rats with non-alcoholic fatty liver disease

2区 · 医学

Article

作者: Li, Yang ; Gan, Jian-He ; Han, Li-Bing ; Jiang, Hai-Tao ; Xiao, Li

PURPOSEThis study aims to explore the relationship between miR-195 and CD40 and its effect on Th17/Treg balance in rats with non-alcoholic fatty liver disease (NAFLD).METHODSWe established rat models of NAFLD and made seven groups, Normal group (without modeling), Model group (model rats), NC group (model rats injected with negative control vector), miR-195 OE group (model rats injected with miR-195 mimic), anti-miR-195 group (model rats injected with miR-195 inhibitor), Si-CD40 group (model rats injected with CD40 silencing vector), and anti-miR-195+Si-CD40 group (model rats injected with miR-195 inhibitor and CD40 silencing vector). Dual-luciferase reporter gene assay verified the targeting relationship between miR-195 and CD40. The mRNA and protein expression levels of miR-195, CD40 as well as Th17/Treg associated cytokines in the liver tissues were detected. The pathological changes of liver tissues were detected, and the liver lesion scoring was carried out. The liver coefficient was calculated. The levels of liver function related indices, and Th17/Treg associated cytokines and inflammatory factors in serum were determined. The proportions of Th17/Treg cells in serum were determined by flow cytometry.RESULTSCompared with Normal group, miR-195 expression level in liver tissues of rats in other six groups was significantly reduced (all P < 0.05); the serum levels of AST, ALT, GGT, IL-17, TNF-α, IL-23, IL-6, IL-8, TC, TG, HDL, and LDL, and the Th17/Treg ratio, as well as the mRNA and protein expression levels of CD40, RORyt, IL-17, TNF-α, IL-23, and IL-8 in liver tissues were significantly increased (all P < 0.05); while the mRNA and protein expression levels of Foxp3, and IL-10 level were significantly reduced (all P < 0.05). Compared with Model group, the above parameters showed an opposite trend in miR-195 OE group and Si-CD40 group were significantly reduced (all P < 0.05). Moreover, anti-miR-195 group could aggravate the imbalance of Th17/Treg cells in rats with NAFLD and promote inflammatory response. Compared with anti-miR-195 group, the combined treatment in anti-miR-195+Si-CD40 group can partially avoid the imbalance of Th17/Treg cells, and inhibit inflammatory response.CONCLUSIONOverexpression of miR-195 can reduce the Th17/Treg ratio to maintain Th17/Treg balance by inhibiting CD40 expression in rats with NAFLD.

2019-08-01·Life Sciences3区 · 医学

LncRNA MALAT1 promotes tumorigenesis and immune escape of diffuse large B cell lymphoma by sponging miR-195

3区 · 医学

Article

作者: Huang, Yan-Fang ; Song, Yuan ; Lian, Guang-Yu ; Wang, Qing-Ming ; Gong, Yi

BACKGROUNDPD-L1 enhanced the tumorigenesis and immune escape abilities of cancers. The upstream mechanisms of PD-L1 in regulating tumorigenesis and immune escape of diffuse large B cell lymphoma (DLBCL) remained unclear.METHODSHuman DLBCL cell line OCI-Ly10 and DLBCL patient samples were used in this study. MALAT1 was knocked down by shRNA. MiR-195 was inhibited by miR-195 inhibitor. Levels of MALAT1, PD-L1, miR-195 and CD8 were detected by RT-qPCR. Protein levels of PD-L1, Ras, p-ERK1/2, ERK1/2, Slug, E-cadherin, N-cadherin, Vimentin were detected by western blotting. The interaction between MALAT1 and miR-195, miR-195 and PD-L1 were detected by luciferase assay. OCI-Ly10 cell proliferation and apoptosis were detected by MTT and Annexin V/PI assays, respectively. Migration was detected by transwell assay. Cytotoxicity of CD8⁺ T cells was detected by LDH cytotoxicity kit. Proliferation and apoptosis of CD8⁺ T cell co-cultured with OCI-Ly10 cells were analyzed by CFSE and Annexin V/PI staining.RESULTSMALAT1, PD-L1 and CD8 were up-regulated in DLBCL tissues while miR-195 was down-regulated. MiR-195 was negatively correlated with MALAT1 and PD-L1. MALAT1 could sponge miR-195 to regulate the expression of PD-L1. shMALAT1 treatment increased miR-195 level and decreased PD-L1 level. It also inhibited cell proliferation, migration and immune escape ability while increased apoptosis ratio of OCI-Ly10 cells. shMALAT1 treatment in OCI-Ly10 cells also promoted proliferation and inhibited apoptosis of CD8⁺ T cells. Knocking down of MALAT1 also suppressed EMT-like process via Ras/ERK signaling pathway. These effects were all rescued by miR-195 inhibitor.CONCLUSIONLong non-coding RNA MALAT1 sponged miR-195 to regulate proliferation, apoptosis and migration and immune escape abilities of DLBCL by regulation of PD-L1.

100 项与 miR-195 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
颈动脉狭窄	临床前	中国	高雄医学大学	-
缺血性卒中	临床前	中国	高雄医学大学	-
结直肠癌	药物发现	中国	高雄医学大学	-
宫颈癌	药物发现	中国	高雄医学大学	-