BMC GASTROENTEROLOGY
·
2023
·Vol. 23
·期 1
·1-10
·
IF 2.4
Xiang Ping,Ge Tingrui,Zhou Jingyi,Zhang Yonggang
Background Increasing research indicates that circular RNAs (circRNAs) play critical roles in the development of ulcerative colitis (UC). This study aimed to determine the role of circRNA CCND1 in UC bio-progression, which has been shown to be downregulated in UC tissues. Methods Reverse transcription quantitative polymerase chain reaction was used to determine the levels of circRNA CCND1 , miR-142-5p, and nuclear receptor coactivator-3 ( NCOA3 ) in UC tissues and in lipopolysaccharide (LPS)-induced Caco-2 cells. Target sites of circRNA CCND1 and miR-142-5p were predicted using StarBase, and TargetScan to forecast potential linkage points of NCOA3 and miR-142-5p, which were confirmed by a double luciferase reporter-gene assay. Cell Counting Kit 8 and flow cytometry assays were performed to assess Caco-2 cell viability and apoptosis. TNF-α, IL-1β, IL-6, and IL-8 were detected using Enzyme-Linked Immunosorbent Assay kits. Results CircRNA CCND1 was downregulated in UC clinical samples and LPS-induced Caco-2 cells. In addition, circRNA CCND1 overexpression suppressed LPS-induced apoptosis and inflammatory responses in Caco-2 cells. Dual-luciferase reporter-gene assays showed that miR-142-5p could be linked to circRNA CCND1 . Moreover, miR-142-5p was found to be highly expressed in UC, and its silencing inhibited LPS-stimulated Caco-2 cell apoptosis and inflammatory responses. Importantly, NCOA3 was found downstream of miR-142-5p. Overexpression of miR-142-5p reversed the inhibitory effect of circRNA CCND1 -plasmid on LPS-stimulated Caco-2 cells, and the effects of miR-142-5p inhibitor were reversed by si- NCOA3 . Conclusion CircRNA CCND1 is involved in UC development by dampening miR-142-5p function, and may represent a novel approach for treating UC patients.
研究领域:
分子生物学
·
胃肠病学
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免疫学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Jing Lv,Guangyu Liu,Huimin Gao,Yutao He,Xiaorong Tang,Ziqi Wang,Kaikai Sun,Kulbaram Bayazitova,Zhongliang Jiang
Trehalose, as a food and feed additive, can regulate physiological and pathological processes by activating autophagy, yet the molecular mechanism of trehalose dominated a rise in autophagy has not been elucidated. This study investigated the mechanisms of trehalose-induced autophagy in porcine granulosa cells (PGCs). Trehalose was internalized into PGCs by endocytosis and caused a temporary change of the lysosome pH, ultimately inducing autophagy. Furthermore, miRNA-seq analysis of PGCs indicated that trehalose upregulated the expression of miR-221-5p_R-4, which can target nuclear receptor binding factor 2 (NRBF2) to induce autophagy of PGCs. In summary, this study reveals that miR-221-5p_R-4 targeting NRBF2 was involved in the autophagy of PGCs challenged by trehalose, which was taken up by PGCs through endocytosis.
研究领域:
分子生物学
·
细胞生物学
·
生殖生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AQUATIC TOXICOLOGY
·
2017
·
IF 4.129
Jiebo Lin,Caihong Wang,Jinfeng Liu,Randy A. Dahlgren,Weiming Ai,Aibing Zeng,Xuedong Wang,Huili Wang
Triclosan (TCS) exposure has widely adverse biological effects such as influencing biological reproduction and endocrine disorders. While some studies have addressed TCS-induced expression changes of miRNAs and their related down-stream target genes, no data are available concerning how TCS impairs miRNA expression leading us to study up-stream regulating mechanisms. Four miRNAs (miR-125b, miR-205, miR-142a and miR-203a) showed differential expression between TCS-exposure treatments and the control group; their functions mainly involved fatty acid synthesis and metabolism. TCS exposure led to the up-regulation of mature miR-125b that was concomitant with consistent changes in pri-mir-125b-1 and pri-mir-125b-3 among its 3 pri-mir-125bs. Up-regulation of miR-125b originated from direct shear processes involving the two up-regulated precursors, but not pri-mir-125b2. Increased expression of pri-mir-125b-1 and pri-mir-125b-3 resulted from nfe2l2- and c/ebpα-integration with positive control elements of promoters for the two precursors. The overexpression of transcriptional factors, nfe2l2 and c/ebpα, initiated the promoter activity for the miR-125b precursor. CpG islands and Nfe2l2 were involved in constitutive expression of mir-125b-1 and mir-125b-3 . The activities of two promoter regions, −487 to −1 bp for pri-mir-125b1 and −1327 to +14 bp for pri-mir-125b-3 having binding sites for NFE2 and Nfe2l2/MAF:NFE2, were higher than other regions, further demonstrating that the transcriptional factor Nfe2l2 was involved in the regulation of pri-mir-125b1 and pri-mir-125b-3. TCS’s estrogen activity resulted from its effects on GPER, a novel membrane receptor, rather than the classical ERα and ERβ. These results explain, to some extent, the up-stream mechanism for miR-125b up-regulation, and also provide a guidance to future mechanistic study on TCS-exposure.
研究领域:
毒理学
·
分子生物学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2022
·Vol. 101
·期 3
·550-567
·
IF 2.873
Wenlin Lu,Xuhui Liu,Linghui Zhao,Shirong Yan,Qingyun Song,Cao Zou,Xun Li
Heart failure (HF) is often the inevitable manifestation of myocardial ischemia. Hypoxia can induce cardiomyocytes to express many microRNAs (miRNAs), which are highly expressed in exosomes. In addition, miR-22-3p is a marker in heart failure. Therefore, miR-22-3p was taken as the research object to explore its role and mechanism in HF. HF differentially expressed miRNAs were screened by bioinformatic analysis. The HF rats model was constructed and identified by detecting serum brain natriuretic peptide (BNP) and ultrasound analysis [left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS)]. The extracted exosomes were identified by transmission electron microscopy, and Western blot was used to detect the expressions of Tsg101 and CD63. Quantitative real-time polymerase chain reaction detected miR-22-3p expression in serum, exosomes, and serum without exosomes, while the cardiomyocytes cytotoxicity was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and PKH26 staining. After overexpressing/silencing miR-22-3p in cells, cell viability, apoptosis, and apoptosis-associated markers were detected. Bioinformatic analysis screened the target gene of miR-22-3p, which was verified by dual-luciferase assay. Regulation of miR-22-3p on FURIN was measured by rescue tests. In vivo experiments were verified the above results. MiR-22-3p was identified as the research object. BNP was increased in the model group, while LVEF and LVFS were decreased. MiR-22-3p was overexpressed in HF-treated serum and exosomes. Normal exosomes did not affect cardiomyocyte function, while high concentrations of HF-treated exosomes were cytotoxic. By regulating apoptosis-related genes, overexpressed miR-22-3p inhibited cell activity and promoted cell apoptosis. Silenced miR-22-3p with opposite effects counteracted effects of HF-treated exosomes. FURIN, target gene of miR-22-3p, was negatively regulated by miR-22-3p, while overexpressed FURIN promoted cell activity and inhibited apoptosis. In vivo research was consistent with the results of cell experiments. By regulating FURIN, miR-22-3p in exosomes increases the risk of HF damage.
研究领域:
心脏病学
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分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Analytical Chemistry
·
2024
·
IF 1.5
Bingyuan Fan,Qian Wang,Shan Wang,Yahui Gao,Yan Liang,Jinru Pan,Xinrui Fu,Li Li,Wei Meng
MiR-378 is abnormally expressed in various cancers, such as hepatocellular carcinoma, renal cell carcinoma, and nonsmall cell lung cancer. Here, we developed a label- and immobilization-free ratiometric homogeneous electrochemical strategy based on exonuclease III (Exo III) for the facile and rapid determination of miR-378. Two 3′-protruding hairpin DNA probes (HPs) are designed in this strategy. Doxorubicin (DOX) and potassium ferrocyanide (Fe 2+ ) were used as label-free probes to produce a response signal (I DOX ) and a reference signal (I Fe 2+ ) in the solution phase. When no target was present in the solution, the HP was stable, most of the DOX was intercalated in the stem of the HP, and the diffusion rate of DOX was significantly reduced, resulting in reduced electrochemical signal response. When miR-378 was present, double-cycle signal amplification triggered by Exo III cleavage was initiated, ultimately disrupting the hairpin structures of HP1 and HP2 and releasing a large amount of DOX into the solution, yielding a stronger electrochemical signal, which was low to 50 pM. This detection possesses excellent selectivity, demonstrating high application potential in biological systems, and offers simple and low-cost electrochemical detection for miR-378.
研究领域:
生物化学
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分子生物学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Genes
·
2023
·Vol. 14
·期 5
·1011
·
IF 3.5
Lei Yang,Sheng He,Ling Ling,Fangfang Wang,Lei Xu,Lei Fang,Fan Wu,Shuting Zhou,Fan Yang,Hongwei Wei,Duonan Yu
miR-144/451and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulate two antioxidative systems that have been identified to maintain redox homeostasis in erythroid cells by removing excess reactive oxygen species (ROS). Whether these two genes coordinate to affect ROS scavenging and the anemic phenotype, or which gene is more important for recovery from acute anemia, has not been explored. To address these questions, we crossedmiR-144/451knockout (KO) andNrf2KO mice and examined the phenotype change in the animals as well as the ROS levels in erythroid cells either at baseline or under stress condition. Several discoveries were made in this study. First,Nrf2/miR-144/451double-KO mice unexpectedly exhibit similar anemic phenotypes asmiR-144/451single-KO mice during stable erythropoiesis, although compound mutations ofmiR-144/451andNrf2lead to higher ROS levels in erythrocytes than single gene mutations. Second,Nrf2/miR-144/451double-mutant mice exhibit more dramatic reticulocytosis thanmiR-144/451orNrf2single-KO mice during days 3 to 7 after inducing acute hemolytic anemia using phenylhydrazine (PHZ), indicating a synergistic effect ofmiR-144/451and Nrf2 on PHZ-induced stress erythropoiesis. However, the coordination does not persist during the whole recovery stage of PHZ-induced anemia; instead,Nrf2/miR-144/451double-KO mice follow a recovery pattern similar tomiR-144/451single-KO mice during the remaining period of erythropoiesis. Third, the complete recovery from PHZ-induced acute anemia inmiR-144/451KO mice takes longer than inNrf2KO mice. Our findings demonstrate that complicated crosstalk betweenmiR-144/451and Nrf2 does exist and the crosstalk of these two antioxidant systems is development-stage-dependent. Our findings also demonstrate thatmiRNAdeficiency could result in a more profound defect of erythropoiesis than dysfunctional transcription factors.Keywords:miR-144/451;Nrf2;hemolytic anemia;reactive oxygen species
研究领域:
血液学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Toxicology Research
·
2015
·Vol. 5
·期 1
·160-167
·
IF 3.983
Liye Zhu,Tao Yu,Xiaozhe Qi,Bo Yang,Lei Shi,Haoshu Luo,Xiaoyun He,Kunlun Huang,Wentao Xu
OTA can induce hepatotoxicity. Our previous research has shown that miRNAs play important roles in the OTA-induced hepatotoxicity. And miR-122 is the most abundant miRNA in the liver and is involved in diverse biological processes. This study was performed to clarify the role of miR-122 in OTA-induced hepatotoxicity. The expression levels of miR-122 and the target genes were quantified by real-time PCR. The OTA-induced apoptosis of hepatocyte and HepG2 cells was evaluated using a TUNEL kit, a CCK-8 kit, a flow cytometer and Hoechst 33342. miR-122 was inhibited in HepG2 cells. The results revealed that OTA affected rat hepatocyte apoptosis. miR-122 decreased at 4 weeks but increased at 13 weeks in the OTA-treated livers, and increased in the OTA-treated HepG2 cells; and the mRNA levels of CCNG1 and Bcl-w increased at 4 weeks and decreased at 13 weeks in the high-dose OTA-treatment groups and decreased in HepG2 cells. The apoptosis of HepG2 cells displayed a dose-related increase with OTA. However, the inhibition of miR-122 greatly reduced OTA-induced apoptosis. p53 decreased in vivo and in vitro. miR-122 is a primary effector of OTA-induced hepatocyte apoptosis through the CCNG1/p53 pathway and Bcl-w/caspase-3 pathway in vivo and in vitro. And miR-122 plays an important role in OTA-induced hepatotoxicity.
研究领域:
分子生物学
·
毒理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED GENETICS
·
2025
·
IF 1.9
Li Yan,Zhou Hongwei,Yao Yibing,Fan Zaiwen
Lung squamous cell carcinoma (LUSC) is one of the major subtypes of lung cancer. Non-SMC condensin I complex subunit H (NCAPH) is highly regarded as a valuable biomarker in certain malignant tumors. However, the specific roles of NCAPH in LUSC are not well understood. The objective of this work was to determine the effect of NCAPH on the progression of LUSC and to identify the microRNAs (miRNAs) located upstream of NCAPH that regulate its function. MicroRNA and mRNA expression profiles, as well as clinical data of LUSC (Normal: 49, LUSC: 502), were obtained from the TCGA database for the purpose of differential analysis and survival analysis. The expression of NCAPH and miR-1976 in LUSC cell lines was detected using Quantitative reverse transcription PCR (qRT-PCR) and western blot techniques. In this study, the impact of NCAPH on the proliferation of LUSC cells was assessed using CCK-8 and colony formation assay. Additionally, the effects of NCAPH on the migration and invasion of LUSC cells were evaluated using the Transwell assay. Furthermore, the effects of NCAPH on the apoptosis of LUSC cells were evaluated using flow cytometry. The target miRNAs of NCAPH were predicted using bioinformatics, and the targeting link between miR-1976 and NCAPH was confirmed using a dual-luciferase reporter gene experiment. The findings indicated that the expression of NCAPH was notably elevated in LUSC tissues ( P < 0.05), while the expression of its upstream miRNA (miR-1976) was notably reduced ( P < 0.05). The dual-luciferase test results indicated that miR-1976 functions as an upstream target miRNA of NCAPH. Low expression of NCAPH may inhibit the proliferation ( P < 0.05), migration ( P < 0.05), invasion ( P < 0.05), and promote apoptosis ( P < 0.05) in LUSC cells. However, the suppression of miR-1976 may reverse this inhibitory effect by specifically targeting NCAPH. This study showed that NCAPH can serves as a novel potential oncogenic biomarker for LUSC and its regulation is controlled by upstream miR-1976. miR-1976 can directly targets NCAPH to affect the proliferation, migration, invasion, and apoptosis of LUSC cell.
研究领域:
分子生物学
·
癌症研究
·
生物信息学
·
遗传学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2025
·
IF 3.8
Xiaomin Ye,Peiqu Zhong,Qiongfang Chen,Dongmei Zhou,Jieyu Luo,Youcai Liang,Jiayuan Zhang,Lijian Zhao
The widespread use of perfluorooctanesulfonic acid (PFOS) has raised concerns regarding its potential on pregnant women, particularly in relation to the development of pre-eclampsia (PE). This study investigates the impact of PFOS exposure on the LncRNA/Rnd3 axis in pregnant mice and its association with trophoblast cell functions in PE. Bioinformatics analysis revealed PFOS-related gene alterations in PE, with pathways enriched in apoptotic signaling and cytokine interactions. Experimental findings showed the downregulation of Oip5os1 and Rnd3, along with the upregulation of miR-155, affecting trophoblast behavior. Animal experiments confirmed that PFOS-induced gene expression changes are linked to PE progression. PFOS exposure impairs trophoblast proliferation and migration via the Oip5os1/miR-155/Rnd3 axis, contributing to PE development.
研究领域:
毒理学
·
生殖生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-18
·
IF 12.6
Wang Yingqian,Ma Zeqiang,Jiang Lehua,Bojan Nataraj,Sha Yiwen,Huang Boyu,Ming Lianxi,Shen Junnan,Pang Weijun
Background Skeletal muscle lipid deposition is a key manifestation of obesity, often accompanied by decreased exercise capacity and muscle atrophy. Skeletal muscle as the largest organ in the body, makes it challenges for designing targeted drug delivery systems. Lipid nanoparticles (LNPs) are widely used as a safe and efficient delivery carrier, there is limited research on LNPs that specifically target skeletal muscle. Results A LNP designed with five specific receptor complements on its surface, which specifically targets skeletal muscle in vivo in mice, without off-target effects on other tissues and organs. MiR-130a, a regulator of PPARG, which is a key factor in skeletal muscle lipid deposition, was encapsulated with LNP (LNP@miR-130a). In high-fat diet (HFD) mice, LNP@miR-130a effectively reduced skeletal muscle lipid deposition, increased exercise activity and enhanced muscle mass. Interestingly, the myokines in skeletal muscle have also changed which may leading to reduce the adipose tissue weight and liver lipid deposition in HFD mice. Conclusions These results indicated LNP@miR-130a is a promising inhibitor of skeletal muscle lipid deposition and may help alleviate obesity. This study provides new insights for obesity treatment and lays foundation for the development of targeted skeletal muscle therapeutics. Graphical
研究领域:
生物医学
·
分子生物学
·
药剂学
✓ 已验证
DOI
PubMed
高影响因子
TECHNOLOGY IN CANCER RESEARCH & TREATMENT
·
2020
·
IF 2.074
Feng Xia,Wei Xia,Xudong Yu
Objective:The study was aim to investigate the effect of HOX transcript antisense RNA (HOTAIR) on the growth, migration, and invasion of papillary thyroid carcinoma (PTC) and its underlying mechanisms.Methods:Cell growth, invasion, and migration was respectively investigated using the MTT assay, trans-well assay, and wound healing assay. The expression of genes and proteins was respectively determined by Western blot analysis and RT-PCR experiments.Results:It was demonstrated that high expression of HOTAIR in PTC cells (BCPAP) and tissues resulted in fast tumor growth and poor survival time of the PTC-bearing mice models. Moreover, overexpression of HOTAIR leaded to markedly enhanced proliferation, migration, and invasion of BCPAP cells. Increase the levels of HOTAIR in BCPAP cells signally down-regulated the miR-488-5p levels which was able of inhibiting the growth rate, increasing the apoptosis rate, and decreasing the invasion/migration ability of BCPAP cells. Further studies indicated that HOTAIR promoted BCPAP cell growth, invasion, and migration mainly through regulating the miR-488-5p/NUP205 axis and the levels of Bcl-2 as well.Conclusion:HOTAIR promoted the growth, migration, and invasion of papillary thyroid carcinoma mainly through regulating the miR-488-5p/NUP205 axis.
研究领域:
肿瘤学
·
分子生物学
·
遗传学
✓ 已验证
DOI
PubMed
高影响因子
Neural Regeneration Research
·
2022
·Vol. 18
·期 7
·1591
·
IF 6.058
Liu Yu-Tian,Xu Zhao,Liu Wei,Ren Sen,Xiong He-Wei,Jiang Tao,Chen Jing,Kang Yu,Li Qian-Yun,Wu Zi-Han,Machens Hans-GüNther,Yang Xiao-Fan,Chen Zhen-Bing
Circular RNAs (circRNAs) play a vital role in diabetic peripheral neuropathy . However, their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood. Here, we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls. Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group. Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation. A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs. circ_0002538 was markedly downregulated in patients with diabetic peripheral neuropathy . Further in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin (PLLP) expression. Moreover, overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function. The results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p, while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell migration. These findings suggest that the circ_0002538 /miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients, improving myelin sheath structure and nerve function. Thus, this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy .
研究领域:
神经科学
·
分子生物学
·
糖尿病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）