Reproductive Biology
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2023
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IF 2.1
Ganping Lai,Dan Bu,Maolin Chen,Hongfang Liu,Lei Dong
The present study aimed to identify the role of circPLOD2 in endometriosis and its underlying mechanisms. We determined circPLOD2 and miR-216a-5p expression in ectopic endometrial (EC) and eutopic endometrial (EU) samples as well as in endometrial samples from uterine fibroids of ectopic patients (EN) and embryonic stem cells (ESCs) using qRT-PCR. The association between circPLOD2 and miR-216a-5p or miR-216a-5p and zinc finger E-box binding homeobox 1 (ZEB1) expression was analyzed using Starbase, TargetScan, and dual-luciferase reporter gene assays. Cell viability , apoptosis , and migration and invasion were assessed using MTT, flow cytometry, and transwell assays, respectively. In addition, qRT-PCR and western blotting was used to measure circPLOD2, miR-216a-5p, E-cadherin, N-cadherin, and ZEB1 expression. circPLOD2 was upregulated and miR-216a-5p was downregulated in EC samples compared with that in EU samples. Similar trends were observed in ESCs. circPLOD2 interacted and negatively regulated miR-216a-5p expression in EC-ESCs. circPLOD2-siRNA significantly inhibited EC-ESC growth; promoted cellular apoptosis; and inhibited EC-ESC migration, invasion, and epithelial–mesenchymal transition; these effects could be reversed following miR-216a-5p inhibitor transfection. miR-216a-5p directly targeted and negatively regulated ZEB1 expression in EC-ESCs. In conclusion, circPLOD2 promotes the proliferation, migration, and invasion of EC-ESCs and inhibits their apoptosis by targeting miR-216a-5p. These findings indicate potential therapeutic targets for endometriosis.
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JOURNAL OF HUMAN HYPERTENSION
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2020
·Vol. 35
·期 8
·696-708
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IF 2.26
Lv Lingchun,Shen Jiayi,Xu Jian,Wu Xiaoyan,Zeng Chunlai,Lin Li,Mao Wei,Wei Tiemin
Through previous literature studies, we found that miR-124-3p may be associated with hypertension. Therefore, we investigated the relationship between miR-124-3p and hypertension in Human Umbilical Vein Endothelial Cells (HUVECs) induced by angiotensin II (AngII). AngII-induced HUVECs model was constructed and the expression of miR-124-3p was detected by qRT-PCR. After transfected cells, apoptosis and ROS production were detected by flow cytometry, caspase-3 kit, and DCFH-DA staining. The target genes of miR-124-3p were predicted and verified by TargrtScan, Luciferase assay, qRT-PCR, and western blot. After silencing Early growth response factor 1 (siEGR1), its effects on apoptosis and ROS production were explored. Finally, the rescue experiments were conducted to explore the mechanism of miR-124-3p to reduce hypertension. MiR-124-3p was underexpressed in the cell model. In Ang II-induced HUVECs, the number of apoptosis increased, the content of caspase-3 was higher, and ROS production increased. However, these effects could be partially inhibited by miR-124-3p mimic. EGR1 was down-regulated by miR-124-3p, and siEGR1 was able to inhibit apoptosis and ROS production of cell model. In the final rescue experiments, miR-124-3p partially reversed the effect of Ang-II on the viability, migration, invasion and apoptosis and ROS production in HUVECs by down-regulating EGR1. MiR-124-3p inhibits Ang II-induced apoptosis and ROS production in HUVECs by down-regulating EGR1.
研究领域:
心血管研究
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分子生物学
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细胞生物学
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ENDOCRINE JOURNAL
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2019
·
IF 1.94
Lili Zhuang,Hongmei Qu,Jianxiang Cong,Huangguan Dai,Xiaoyan Liu
MicroRNAs (miRNAs), which is a type of non-coding and single-stranded small molecule RNA, bind either completely or incompletely to 3’-UTR of the target gene mRNA to inhibit mRNA translation or degradation. In our study, we aimed to explore the roles and mechanisms of miR-181c in the apoptosis of RL95-2 human endometrial carcinoma cells. Cell activity and apoptosis were detected by cell counting Kit-8 (CCK-8) assay and flow cytometry (FCM), respectively. Related mRNAs and proteins expression was determined by quantitative real-time reverse transcription PCR (qRT-PCR) and western blot assays, respectively. The binding capacity of PTEN-3’-UTR and miR-181c was assessed by luciferase reporter assay. The obtained results suggested that E2 evidently increased the cell activity of RL95-2 cells. In addition, miR-181c inhibitor suppressed the cell viability and enhanced the apoptosis capacity of E2-induced RL95-2 cells and distinctly reduced the miR-181c expression. We also found that miR-181c could bind to PTEN-3’-UTR and miR-181c inhibitor up-regulated the expression level of PTEN in E2-induced RL95-2 cells. Besides, overexpression of PTEN markedly promoted the apoptosis of E2-induced RL95-2 cells through regulating the Bax and Bcl-2 expression, and modulated the expression of AKT pathway, p53 and Cyclin D. In conclusion, our findings revealed that miR-181c affected the estrogen-dependent endometrial carcinoma cell growth by targeting PTEN. The potential effects of miR-181c on the apoptosis of E2-induced RL95-2 cells suggest that miR-181c could be an effective target for endometrial carcinoma therapies.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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Cancer Management and Research
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2020
·
IF 2.886
Peiqiang Jiang,Wei Han,Yu Fu,Qingmin Chen
Purpose: Circular RNAs (circRNAs) play important roles in hepatocellular carcinoma (HCC) development. The circRNA hsa_circ_0091579 (circ_0091579) is dysregulated in HCC, while the mechanism of circ_0091579 in HCC development is largely unknown.Patients and Methods: Thirty paired cancer and adjacent normal tissues were harvested from HCC patients. SNU-387 and Huh7 cells were cultured in this study. circ_0091579, microRNA-940 (miR-940) and tachykinin-1 receptor (TACR1) abundances were measured via quantitative reverse transcription-polymerase chain reaction or Western blot. Cell viability, migration, invasion, colony ability, cell cycle distribution and apoptosis were assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, transwell assay, colony formation assay and flow cytometry. The interaction among circ_0091579, miR-940 and TACR1 was tested via dual-luciferase reporter analysis. The anti-HCC role of circ_0091579 knockdown in vivo was investigated using xenograft model.Results: circ_0091579 expression was enhanced in HCC tissue samples and cells. circ_0091579 silence inhibited cell viability, migration, invasion and colony formation, induced cell cycle arrest at G0/G1 phase, and promoted apoptosis in HCC cells. miR-940 was targeted via circ_0091579 and miR-940 knockdown reversed the suppressive effect of circ_0091579 silence on HCC development. miR-940 targeted TACR1 to repress HCC development. circ_0091579 could regulate TACR1 expression by mediating miR-940. Down-regulation of circ_0091579 decreased xenograft tumor growth.Conclusion: Knockdown of circ_0091579 repressed HCC development by mediating miR-940/TACR1 axis, indicating a new pathogenesis of HCC.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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Food Bioscience
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2023
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IF 5.2
Hengju Ge,Jiaxin Li,Yang Xu,Jiahong Xie,Naymul Karim,Fujie Yan,Jianling Mo,Wei Chen
Curcumin (CUR), the main compound extracted from Curcuma longa , has various biological actions, including hepatoprotective, anti-infective, anti-inflammatory, antioxidant, and neurotrophic properties. But it has not yet been clarified how CUR affects the accumulation of fatty in hepatic cells. Our study uncovered that CUR decreased the lipid deposition in free fat acids (FFAs)-treated hepatocytes, which could be blocked by Compound C (an AMPK inhibitor). This result suggests that protective effect was associated with the AMPK pathway activation. MiR-3666 directly targets the AMPK gene, and overexpression of miR-3666 greatly weakens the hypolipidemic effect of CUR. Our results showed that CUR reduced FFAs-induced lipid deposition by targeting miR-3666. This boosted AMPK phosphorylation and inhibited its downstream targets, including ACC and SREBP1 . These findings together confirm that CUR-mediated inhibition of miR-3666 to activate the AMPK pathway is a potential alternative for alleviation of hepatic lipid deposition.
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JOURNAL OF PSYCHOPHARMACOLOGY
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2018
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IF 4.738
Li-Tao Yi,Rong-Hao Mu,Shu-Qi Dong,Shuang-Shuang Wang,Cheng-Fu Li,Di Geng,Qing Liu
Our previous study demonstrated that gypenosides produced antidepressant-like effects in mice exposed to chronic mild stress in a brain-derived neurotrophic factor-dependent manner. However, whether other mechanisms are involved in the antidepressant-like effects of gypenosides is not clear. miR-124 is one of the most abundant microRNAs in the hippocampus, and its dysregulation is related to the pathophysiology of depression. The glucocorticoid receptor is dysfunctional in depression, and it is a direct target of miR-124. Therefore, the present study used corticosterone-induced mice as a model to evaluate the role of miR-124 on the antidepressant-like effects of gypenosides. miR-124 agomir was intracerebrally injected prior to administration of gypenosides and corticosterone injection. Sucrose preference and forced swimming tests were performed 21 days later. Proteins related to glucocorticoid receptors and brain-derived neurotrophic factor-tyrosine receptor kinase B signaling in the hippocampus were evaluated. Our results demonstrated that gypenosides reversed the chronic corticosterone injection-induced decreased sucrose preference and increased immobility time. In contrast, this effect was antagonized by miR-124 injection. In addition, gypenosides increased glucocorticoid receptor and tyrosine receptor kinase B expression in the hippocampus, which activated brain-derived neurotrophic factor signaling. miR-124 also blocked these effects. In conclusion, this study demonstrated that a reduction in miR-124 was required for the antidepressant-like effects of gypenosides induced by chronic corticosterone injection in mice.
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JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
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2021
·Vol. 31
·期 11
·1508-1518
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IF 2.351
Bao Yuyan,Yu Yanjie,Hong Bing,Lin Zhenjian,Qi Guoli,Zhou Jie,Liu Kaiping,Zhang Xiaomin
Hsa_circ_0001947 is associated with multiple cancers, but its function in non-small cell lung cancer (NSCLC) is ambiguous and needs further research. The targeting relationship among circ_0001947, miR-661, and downstream of tyrosine kinase 7 (DOK7) was predicted by database and further verified by dual-luciferase reporter assay, while their expressions in cancer tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). After transfection, cell biological behaviors and expressions of miRNAs, miR-661 and DOK7 were determined by cell function experiments and qRT-PCR, respectively. Circ_0001947 was low-expressed in NSCLC tissues and cells. Circ_0001947 knockdown intensified cell viability and proliferation, induced cell cycle arrest at S phase, suppressed apoptosis and evidently enhanced miR-510, miR-587, miR-661 and miR-942 levels, while circ_0001947 overexpression did the opposite. MiR-661 was a target gene of circ_0001947 that participated in the regulation of circ_0001947 on cell biological behaviors. Furthermore, DOK7, the target gene of miR-661, partly participated in the regulation of miR-661 on cell viability. Hsa_circ_0001947 acts as a sponge of miR-661 to repress NSCLC development by elevating the expression of DOK7.
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World Journal of Surgical Oncology
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2021
·Vol. 19
·期 1
·1-14
·
IF 2.754
Zhang Weitong,Wang Zhenfen,Cai Guohao,Huang Ping
Background Circular RNAs (circRNAs) take part in colorectal cancer malignancies. CircRNA dedicator of cytokinesis 1 (circ_DOCK1) is involved in colorectal cancer progression, but the mechanism underlying this circRNA that takes part in colorectal cancer development remains largely undetermined.Methods Tumor and normal para-cancerous tissues were collected from 42 colorectal cancer patients. Human colorectal cancer cell lines (HCT116 and SW480) were used for the experiments in vitro. Circ_DOCK1, microRNA (miR)-132-3p, and ubiquitin-specific protease 11 (USP11) levels were measured through quantitative real-time polymerase chain reaction and Western blotting. Cell growth, metastasis, and apoptosis were investigated via colony formation, 5-ethynyl-2′-deoxyuridine (EdU) staining, MTT, flow cytometry, Western blotting, and transwell analyses. The target association was evaluated via dual-luciferase reporter analysis, RNA pull-down, and immunoprecipitation (RIP). Xenograft assay was performed using HCT116 cells. USP11 and Ki67 levels in tumor tissues were detected via immunohistochemistry.Results Circ_DOCK1 expression was enhanced in colorectal cancer tissues and cells. Silencing circ_DOCK1 repressed cell growth, migration, and invasion, and facilitated apoptosis. Circ_DOCK1 sponged miR-132-3p, and miR-132-3p silence mitigated the effect of circ_DOCK1 interference on cell growth, metastasis, and apoptosis. MiR-132-3p targeted USP11, and circ_DOCK1 could regulate USP11 level by miR-132-3p. MiR-132-3p suppressed cell growth, metastasis, and apoptosis, and USP11 attenuated these effects. Knockdown of circ_DOCK1 decreased colorectal cancer cell xenograft tumor growth.Conclusion Circ_DOCK1 interference suppressed cell growth and metastasis, and increased apoptosis of colorectal cancer via decreasing USP11 by increasing miR-132-3p.
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COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
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2021
·
IF 3.228
Hui Li,Guilan Di,Yi Zhang,Junping Liang,Xianfeng Wang,Zhenshan Xu,Xianghui Kong
MicroRNAs (miRNAs) play a critical role in regulating the response of animals exposed to heavy metal stress. As a globally dispersed heavy metal in aquatic ecosystems , cadmium (Cd) is highly toxic to many aquatic species . However, little is known about the miRNA response to Cd stress in fish. To investigate the regulatory effect of miRNAs in response to Cd, common carp ( Cyprinus carpio ) were exposed to Cd 2+ -containing water (0.005 mg/L, 0.05 mg/L, 0.5 mg/L) for 30 days. After exposure, Cd 2+ contents were significantly higher in the kidneys of C. carpio compared to other tissues, when exposed to 0.5 mg/L Cd 2+ . Hematoxylin and eosin staining images revealed that elevated Cd induced inflammatory damage in the kidneys of C.carpio . Further, miRNA sequencing revealed nine differentially expressed miRNAs (miR-217, miR-205 and seven novel miRNAs) in the kidneys, between 0.5 mg/L Cd 2+ exposure and control groups. Potential target mRNAs of miRNAs suggest that miR-217 is involved in immunotoxicity . miR-217 agomir was intraperitoneally administered to C. carpio and RT-PCR revealed that the expression of IL-8 and SIRT1 decreased, while TLR-4, TRAF6 , NF-kB, TNF-α, IL-1β, and TGF-β increased in the kidneys of C.carpio . Additionally, the expression of SIRT1 decreased, while the expression of other mRNAs increased in kidneys of C. carpio exposed to Cd. According to mRNAs expression in the agomir and Cd treatment, miRNAs inhibit the expressions of target mRNAs. These results demonstrate that miR-217 via SIRT1 plays a regulatory role in the immunotoxicity of Cd to C. carpio .
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CANCER BIOLOGY & THERAPY
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2020
·
IF 3.659
Chunhua Zhou,Wencheng Kong,Tongfa Ju,Qi Xie,Lulu Zhai
Background Studies showed that microRNAs (miRNAs) are important regulators in drug resistance. The current study investigated the role of miR-185-3p and its predicted target gene AQP5 in 5-FU-insensitive colorectal cancer (CRC) cells.Methods Quantitative real-time polymerase chain reaction (qRT-PCR) and Spearman’s correlation analysis were conducted to determine the correlation of expression levels of miR-185-3p and AQP5 from CRC tissues. HCT-116 and HCT-8 cells were treated by gradient concentration of 5-FU to construct 5-FU-resistant CRC model. The inhibition and viability of 5-FU-resistant cells were detected by MTT assay, and cell migration and invasion ability were determined by wound healing and transwell assay. The expressions of miR-185-3p and AQP5 were measured by qRT-PCR. StarBase and dual-luciferase reporter assay were used to predict and confirm the interaction between miR-185-3p and AQP5. Further experiments were performed to explore the function of miR-185-3p in 5-FU-resistant cells through regulating aquaporin-5 (AQP5). The levels of EMT-associated markers and AQP5 were determined by conducting Western Blot and qRT-PCR.Results We found that 5-FU-resistant CRC cells showed a lower inhibition rate, and higher migration and invasion abilities. MiR-185-3p was low-expressed in CRC tissues and 5-FU-resistance cells, and it targeted and regulated the expression of AQP5, which was found up-regulated in CRC and 5-FU-resistance CRC cells (r = −0.29, P < .05). Furthermore, miR-185-3p mimic enhanced the chemo-sensitivity of 5-FU-resistant cells, while overexpressed AQP5 reversed such an effect produced by miR-185-3p mimic.Conclusion MiR-185-3p mimic enhances the chemosensitivity of CRC cells via AQP5. Our research provides a potential therapeutic target for 5-FU-resistant CRC cells.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2019
·
IF 3.585
Guangxu Cao,Shuang Li,Hezhan Shi,Peidi Yin,Jialing Chen,Huifeng Li,Ying Zhong,Li-Ting Diao,Bin Du
Tubulointerstitial fibrosis (TIF) is the main pathologic feature of end-stage renal disease. Epithelial-mesenchymal transition (EMT) of proximal tubular cells (PTCs) is one of the most significant features of TIF. MicroRNAs play critical roles during EMT in TIF. However, whether miRNAs can be used as therapeutic targets in TIF therapy remains undetermined. We found that miR-30e, a member of the miR-30 family, is deregulated in TGF-β1-induced PTCs, TIF mice and human fibrotic kidney tissues. Moreover, transcription factors that induce EMT, such as snail, slug, and Zeb2, were direct targets of miR-30e. Using a cell-based miR-30e promoter luciferase reporter system, Schisandrin B (Sch B) was selected for the enhancement of miR-30e transcriptional activity. Our results indicate that Sch B can decrease the expression of snail, slug, and Zeb2, thereby attenuating the EMT of PTCs during TIF by upregulating miR-30e, both in vivo and in vitro. This study shows that miR-30e can serve as a therapeutic target in the treatment of patients with TIF and that Sch B may potentially be used in therapy against renal fibrosis
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MOLECULAR PHARMACEUTICS
·
2019
·
IF 4.396
Huanling Guo,Ming Xu,Zhong Cao,Wei Li,Lida Chen,Xiaoyan Xie,Wei Wang,Jie Liu
Ultrasound-induced microbubble sonoporation has been shown to effectively improve drug/gene delivery efficiency by enhancing tissue and cell permeability. However, the microscale size and short duration of ultrasound contrast agents limit their accumulation in target areas. Here, a kind of ultrasound-triggered phase-transitioning and size-changing cationic nanodroplet, perfluoropentane/C9F17-PAsp(DET)/miR-122/poly(glutamic acid)-g-MeO-poly(ethylene glycol) (PGA-g-mPEG) ternary nanodroplets (PFP-TNDs/miR-122), was developed to deliver microRNA-122 (miR-122) for hepatocellular carcinoma (HCC) treatment. PFP served as an ultrasound-sensitive core for ultrasound-triggered phase transition and size change from the nanoscale to the microscale. Positively charged C9F17-PAsp(DET) ensured adequate miRNA loading. PGA-g-mPEG, which served as the shell of the nanodroplet, modified the nanodroplets, enhanced their stability in serum, and protected miR-122 from degradation in vivo. The results exhibited that PFP-TNDs/miR-122 has a nanosize diameter (362 ± 15 nm) and remained stable for 24 h. After treatment with PFP-TNDs/miR-122 combined with ultrasound irradiation, the miR-122 expression level was significantly increased by approximately 600-fold in HepG2 cells, 500-fold in SMMC-7721 cells, and 30-fold in human HCC xenografts. Moreover, PFP-TNDs/miR-122 combined with ultrasound radiation effectively suppressed the growth, migration, and invasion of HCC cells, and inhibited tumor proliferation in mice. This study revealed that the biodegradable PFP-TNDs is a promising therapeutic gene carrier with functions of gene protection and effective gene delivery for clinical applications. Furthermore, PFP-TNDs/miR-122 associated with ultrasound irradiation may pave a new way to improve the prognosis of patients with HCC.
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