Cardiovascular Therapeutics
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2022
·
IF 3.368
Sheng Wang,Zhaoyun Cheng,Xianjie Chen,Guoqing Lu,Xiliang Zhu,Gaojun Xu
Objective. Long noncoding RNAs (lncRNAs), including some members of small nucleolar RNA host gene (SNHG), are important regulators in myocardial injury, while the role of SNHG4 in myocardial infarction (MI) is rarely known. This study is aimed at exploring the regulatory role and mechanisms of SNHG4 on MI. Methods. Cellular and rat models of MI were established. The expression of relating genes was measured by qRT-PCR and/or western blot. In vitro, cell viability was detected by MTT assay, and cell apoptosis was assessed by caspase-3 level, Bax/Bcl-2 expression, and/or flow cytometry. The inflammation was evaluated by TNF-α, IL-1β, and IL-6 levels. The myocardial injury in MI rats was evaluated by echocardiography, TTC/HE/MASSON/TUNEL staining, and immunohistochemistry (Ki67). DLR assay was performed to confirm the target relationships. Results. SNHG4 was downregulated in hypoxia-induced H9c2 cells and MI rats, and its overexpression enhanced cell viability and inhibited cell apoptosis and inflammation both in vitro and in vivo. SNHG4 overexpression also decreased infarct and fibrosis areas, relieved pathological changes, and improved heart function in MI rats. In addition, miR-148b-3p was an action target of SNHG4, and its silencing exhibited consistent results with SNHG4 overexpression in vitro. DUSP1 was a target of miR-148b-3p, which inhibited the apoptosis of hypoxia-induced H9c2 cells. Both miR-148b-3p overexpression and DUSP1 silencing weakened the effects of SNHG4 overexpression on protecting H9c2 cells against hypoxia. Conclusions. Overexpression of SNHG4 relieved MI through regulating miR-148b-3p/DUSP1, providing potential therapeutic targets.
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Bioactive Materials
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2022
·
IF 16.874
Xiaoling Zeng,Baohui Chen,Luping Wang,Yingxiao Sun,Zhao Jin,Xuanyong Liu,Liping Ouyang,Yun Liao
Wound healing is one of the major global health concerns in patients with diabetes. Overactivation of pro-inflammatory M1 macrophages is associated with delayed wound healing in diabetes. miR-29ab1 plays a critical role in diabetes-related macrophage inflammation. Hence, inhibition of inflammation and regulation of miR-29 expression have been implicated as new points for skin wound healing. In this study, the traditional Chinese medicine, puerarin, was introduced to construct an injectable and self-healing chitosan@puerarin (C@P) hydrogel. The C@P hydrogel promoted diabetic wound healing and accelerated angiogenesis, which were related to the inhibition of the miR-29 mediated inflammation response. Compared to healthy subjects, miR-29a and miR-29b1 were ectopically increased in the skin wound of the diabetic model, accompanied by upregulated M1-polarization, and elevated levels of IL-1β and TNF-α. Further evaluations by miR-29ab1 knockout mice exhibited superior wound healing and attenuated inflammation. The present results suggested that miR-29ab1 is essential for diabetic wound healing by regulating the inflammatory response. Suppression of miR-29ab1 by the C@P hydrogel has the potential for improving medical approaches for wound repair.
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CELL CYCLE
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2022
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IF 5.173
Yong Fang,Jun Yin,Yaxing Shen,Hao Wang,Han Tang,Xiaosang Chen
Since circCDR1 was abnormally expressed in esophageal squamous cell cancer (ESCC), the current study explored whether circCDR1 affected ESCC. Detailedly, circCDR1 expression in ESCC and linear isoform and stability of circCDR1 were detected by RT-qPCR. The location of circCDR1 was detected by fluorescence in situ hybridization (FISH). After transfection, the cell biological functions were detected by wound-healing, CCK-8, colony formation, and flow cytometry assays. The target of circCDR1 was predicted by bioinformatics, FISH, RNA pull-down, and dual-luciferase reporter assays. The correlation between circCDR1 and miR-1290 was analyzed by Pearson’s correlation analysis. A subcutaneous-xenotransplant tumor model in BALB/c nude mice was established and the levels of circCDR1, miR-1290, and apoptosis/metastasis/proliferation-related factors in the cancer cells and tissues were detected by immunohistochemical analysis, western blot, or RT-qPCR. As a result, circCDR1 was low-expressed in ESCC tissues and cells, while miR-1290 was high-expressed. CircCDR1 was regulated and was negatively correlated with miR-1290. CircCDR1, located in cytoplasm, inhibited the viability, proliferation, migration, and invasion of the cancer cells and the expressions of Bcl-2, N-cadherin, and Vimentin, but enhanced cell apoptosis and the expressions of C caspase-3, Bax, E-cadherin, IGFBP4, LHX6 and NFIX. In vivo, circCDR1 promoted xenotransplanted tumor weight and volume, and the expressions of C caspase-3 and Bax yet suppressed the levels of Bcl-2, miR-1290, and Ki-67 in tumor tissues. The effects of circCDR1 on both cancer cells and tissues were opposite to and reversed by miR-1290 mimic. Collectively, circCDR1 sponged miR-1290 to regulate the progression of ESCC both in vitro and in vivo.
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DNA AND CELL BIOLOGY
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2022
·Vol. 41
·期 4
·424-436
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IF 3.55
Feng Chi,Fang Qiu,Xiaoming Jin,Long Chen,Guijin He,Sijia Han
Breast cancer (BC) is one of the most frequently occurring malignant tumors in female adults. The long intergenic nonprotein coding RNA 00982 (LINC00982) has been regarded as a cancer suppressor in several human cancers. However, the function and the underlying mechanisms of LINC00982 have not been studied in BC. The present study found that LINC00982 was significantly downregulated in BC tumor tissues, and the low LINC00982 level predicts a poor prognosis of BC. Through the overexpression and suppression of LINC00982 in two BC cell lines, we found that LINC00982 could inhibit cell proliferation, migration, and invasion by suppressing the activity of the signal transducer and activator of transcription 3 (STAT3)/nuclear factor kappa B (NF-κB) signal pathway. Furthermore, luciferase reporter assay has been used to verify that LINC00982 functions as a molecular sponge for miR-765, which could target DPF3. The relative expression of miR-765 decreased with LINC00982 overexpressing, and DPF3 increased at the same time.In addition, the suppression of cell malignant phenotype caused by overexpression of LINC00982 can be reversed by inhibition of DPF3. To verify the function of LINC00982 in vivo, the BC cells were implanted in nude mice and the results suggested the tumor growth and malignant phenotype were suppressed by LINC00982. In this study, we prove that LINC00982 regulates the growth and development of BC through STAT3/NF-κB signal pathway, mediated by the miR-765/DPF3 axis. LINC00982 may function as a target molecule to take part in the prognosis and therapy of BC.
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PATHOLOGY RESEARCH AND PRACTICE
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2022
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IF 3.309
Hong Zhang,Qi Zhou,Jue Jiang
Background Previous data have shown that circular RNA (circRNA) is a key regulator in papillary thyroid cancer (PTC). However, the role and the detailed mechanism of circ_0027446 in PTC progression have not been reported. Methods Circ_0027446, miR-129–5p, claudin 1 (CLDN1), C-myc and MMP2 expression were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western Blot or immunohistochemistry (IHC) assay. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Cell proliferation was investigated by 5-Ethynyl-2′-deoxyuridine (EdU) assay and cell colony formation assay. Cell apoptosis , invasion and migration were assessed by flow cytometry analysis, transwell assay and wound-healing assay, respectively. Dual-luciferase reporter assay was conducted to identify the associations among circ_0027446, miR-129–5p and CLDN1. The effect of circ_0027446 on PTC cell malignancy in vivo was revealed by a xenograft mouse model assay. Results Circ_0027446 and CLDN1 expression were significantly upregulated, while miR-129–5p expression was downregulated in PTC tissues and cells. High circ_0027446 expression was closely associated with the poor prognosis of PTC patients . Circ_0027446 depletion inhibited PTC cell proliferation, migration and invasion but increased cell apoptosis. In addition, circ_0027446 acted as a miR-129–5p sponge, and miR-129–5p bound to CLDN1. Moreover, miR-129–5p inhibitors attenuated circ_0027446 depletion-induced effects in PTC cells. CLDN1 also participated in the regulation of miR-129–5p in PTC cell tumor properties. Importantly, circ_0027446 mediated CLDN1 expression by interacting with miR-129–5p. In vivo data showed that the decreased expression of circ_0027446 led to delayed tumor formation. Conclusion Circ_0027446 contributed to PTC cell tumor properties by regulating the miR-129–5p/CLDN1 pathway, showing circ_0027446 might be a therapeutic target in PTC.
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ANTI-CANCER DRUGS
·
2021
·Vol. 33
·期 1
·e145
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IF 2.248
Liu Dan,Wang Yaya,Li Haiming,Peng Sida,Tan Huo,Huang Zhenqian
Multiple myeloma is a frequent hematologic malignancy. Bortezomib is the first-line drug for multiple myeloma chemotherapy. The present study aimed to investigate the potential role and mechanism of circular RNA chaperonin containing TCP1 subunit 3 (circ-CCT3) in bortezomib resistance of multiple myeloma . The levels of circ-CCT3, microRNA-223-3p ( miR-223-3p ), and bromodomain-containing 4 (BRD4) were detected by quantitative real-time PCR or western blot. Cell Counting Kit-8 (CCK-8) method was used to measure the half-inhibitory concentration of bortezomib and cell viability. Cell cycle distribution, apoptosis, proliferation and migration were determined by flow cytometry, 5-ethynyl-2′-deoxyuridine, and wound healing assay. The levels of relevant proteins were checked via western blot. The binding association between miR-223-3p and circ-CCT3/BRD4 was validated via a dual-luciferase reporter assay. Circ-CCT3 and BRD4 were upregulated, while miR-223-3p was downregulated in bortezomib -resistant multiple myeloma patients and cells. Silencing of circ-CCT3 enhanced the sensitivity of bortezomib -resistant multiple myeloma cells to bortezomib . Circ-CCT3 knockdown weakened bortezomib resistance via modulating miR-223-3p . Moreover, miR-223-3p increased bortezomib sensitivity by inhibiting BRD4. Downregulation of circ-CCT3 attenuated bortezomib resistance of multiple myeloma via regulating miR-223-3p /BRD4 pathway, which provided a new potential target for multiple myeloma chemoresistance.
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EXPERIMENTAL ANIMALS
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2021
·
IF 2.319
Jianhua Wu,Lizhen Wu,Li Zhang,Huanhuan Xu,Min Wang,Lin Wang,Jie Chen,Kaiyue Sun
Inflammatory allergic reaction is the main cause of allergic rhinitis (AR). Previous studies indicated that miR-224-5p was downregulated in the nasal mucosa of patients with AR, while the function of miR-224-5p in AR remains unclear. To explore this issue, AR mouse model was established using ovalbumin (OVA). For treatment group, lentivirus (LV)-miR-224-5p or its control was intranasally administrated to AR mice. miR-224-5p expression was detected by reverse transcription-quantitative PCR, followed by assessing the immunoglobulin E (IgE) level. Pathological alterations in nasal mucosa were detected using Hematoxylin-Eosin staining and Sirius red staining, followed by assessing the levels of inflammatory cells and factors. The NLRP3 inflammasome and TLR4/MyD88/NF-κB pathway were measured by Western blot, and then the relationship between miR-224-5p and toll-like receptor 4 (TLR4) was verified. The results showed that miR-224-5p was significantly decreased in nasal mucosa of AR mice. AR mice exhibited increased sneezing and nasal rubbing events, IgE level in serum, and pathological alterations in nasal mucosa, while overexpression of miR-224-5p markedly attenuated these changes. The levels of inflammatory cells in nasal lavage fluid and pro-inflammatory factors in serum and nasal mucosa were significantly increased in AR mice, which were reduced by miR-224-5p overexpression. Of note, LV-miR-224-5p treatment remarkably suppressed the activations of NLRP3 inflammasome and the TLR4/MyD88/NF-κB pathway in AR mice. Furthermore, miR-224-5p could bind to 3’-untranslated region (3’-UTR) of TLR4 and negatively regulate TLR4 level. Overall, we conclude that miR-224-5p may relieve AR by negatively regulating TLR4/MyD88/NF-κB pathway, indicating that miR-224-5p may be a promising target for AR treatment.
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Frontiers in Molecular Biosciences
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2021
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IF 5.246
Zhang Yin,Wang Qinge,Xu Yuping,Sun Jing,Ding Yanbo,Wang Li,Chen Bingfang,Sun Kewen,Chen Jianping
Benign esophageal strictures (BESs) frequently results from esophageal fibrosis. The transformation of fibroblasts into fibrocyte is an important cause of fibrosis. The treatment of fibrosis is challenging. Some previous studies have indicated the antifibrotic effect of mitomycin C (MMC). However, the mechanism of action of MMC and its optimal dose for treatment remains unclear. In the present study, the role of MMC in fighting fibrosis and its mechanism was investigated. Human esophageal fibroblast cells (HEFs)were treated without or with MMC, at 2, 5, 10 μg/ml, combining with mimic lncRNA-ATB, miR-200b inhibitor, rapamycin (RAPA), and 3-Methyladenine (3-MA). The cell viability, and cell apoptosis were evaluated. In addition, expression of apoptosis related proteins (caspase8 and caspase3), autophagy related proteins (LC3II and ATG5) and fibrosis related proteins (α-SMA collagen-1 and TGF-β) were also evaluated. Furthermore, autophagosome was observed by transmission electron microscope. Results showed that the expression of lncRNA-ATB was down-regulated and miR-200b was up-regulated after treated with MMC. And MMC induced cell apoptosis and inhibited cell autophagy. On the other hand, RAPA, mimic lncRNA-ATB and miR-200b inhibitor reduced fibrogenic effect of MMC on HEFs. Collectively, this study suggests that MMC inhibited esophageal fibrosis by regulating cell apoptosis and autophagy via downregulating lncRNA-ATB and upregulating miR-200b.
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BIOCHEMICAL PHARMACOLOGY
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2021
·
IF 5.858
Xiaodan Tan,Wenjia Guo,Zhe Peng,Chao Gu,Pu Xiang,Yujun Tu,Huizhi Fei,Xia Liu,Yi Lu,Miaomiao Li,Hong Wang,Ying Luo,Junqing Yang
Based on the previous studies, this study was carried out to explore the interaction of LncRNA-Malat1/miR-211-5p in cerebral ischemia reperfusion injury (CIRI). Firstly, the expression changes of LncRNA-MALAT1 and miR-211-5p in ischemia patients’ blood were determined, and the binding sites of them were predicted by bioinformatics. Furthermore, middle cerebral artery occlusion/reperfusion (MCAO/R) injury model was established in adult male SD rats , and primary neuronal oxygen-glucose deprivation/reoxygen-glucose reoxygenation (OGD/R) was established in vitro. The results showed that LncRNA-MALAT1 was significantly up-regulated and miR-211-5p down-regulated in the peripheral blood of patients with ischemic stroke, and the expression changes were negatively correlated. Bioinformatics prediction results showed that LncRNA-MALAT1 had a binding site with miR-211-5p. We also found that LncRNA-Malat1 was significantly up-regulated while miR-211-5p down-regulated in rat cortex tissue and primary neurons treated with OGD/R. In addition, lentivirus interfered with LV-Malat1-RNAi decreased the expression of LncRNA-Malat1 and promoted the up-regulation of miR-211-5p. Combination of LV-Malat1-RNAi and miR-211-5p inhibitor significantly reversed the protective effect of down-regulation of LncRNA-Malat1. Inhibition of LncRNA-Malat1 expression alleviated the neurological deficit score after MCAO/R, improved histopathological damage, and reduced the size of cerebral infarction . Combined administration of LV-Malat1-RNAi + Antagomir-211-5p reversed these effects above. In short, our data suggest that LncRNA-Malat is involved in the occurrence and development of cerebral ischemia reperfusion injury by acting on miR-211-5p and is then regulating the expression of COX-2.
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FOLIA NEUROPATHOLOGICA
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2020
·Vol. 58
·期 1
·10-21
·
IF 1.278
Chengyan Sun,Ning Jia,Rui Li,Ze Zhang,Yi Zhong,Kun Han
IntroductionAlzheimer’s disease (AD) is still the fifth leading cause of death and most common dementia worldwide. To date, there is no efficient strategy that can slow down the progression of AD owing to delayed diagnosis and limited therapies. MiR-143-3p is up-regulated in serum of AD patients, yet the exact role it plays in AD pathology is still poorly understood. The aim of this study was to investigate the effect of miR-143-3p on neuronal survival.Material and methodsWe induced neuronal differentiation in SH-SY5Y cells using all-trans-retinoic acid (RA), and Aβ1-42 was used to establish the in vitro AD cell model. The expression of tubulin β III and neuregulin-1 (NRG1) was evaluated by immunofluorescence. TUNEL assay was performed to assess cell apoptosis. Cell viability was evaluated using the Cell Counting Kit-8 assay. The binding interaction between miR-143-3p and NRG1 was verified using the luciferase reporter assay.ResultsTypical neuronal-like axons were observed in RA-induced SH-SY5Y cells, followed by increased tubulin β III. A dramatically increased apoptotic rate and reduced cell viability were observed in the AD cell model. Then we silenced the miR-143-3p expression, and Aβ1-42 induced cell apoptosis was alleviated after miR-143-3p inhibition, accompanied by decreased cleaved caspase-3 and cleaved caspase-9 levels. Additionally, NRG1 was confirmed to be a downstream target of miR-143-3p, increased cell viability and suppressed cell apoptosis after miR-143-3p inhibition was abolished by NRG1 knockdown.ConclusionsOur findings reveal that miR-143-3p inhibition promotes neuronal survival in an in vitro cell model via targeting NRG1, and the miR-143-3p/NRG1 axis is a potential therapeutic target and promising biomarker for AD treatment.
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EXPERIMENTAL CELL RESEARCH
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2020
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IF 3.383
Guangduo Zhu,Xiaowei Yang,Cheng Peng,Lei Yu,Yingjie Hao
The transplantation of bone marrow mesenchymal stem cells (BMSCs) has been found to be used as an effective therapy of intervertebral disc degeneration (IDD). However, the underlying mechanisms of BMSCs in the progress of IDD are not fully explained. In this study, we found that exosomes derived from BMSCs (BMSCs-Exos) inhibited the apoptotic rate , extracellular matrix (ECM) degradation, and fibrosis deposition in TNF-α-induced nucleus pulposus cells (NPCs). Importantly, the level of miR-532–5p was observed to be decreased in apoptotic NPCs, but abundant in BMSCs-Exos with TNF-α treatment. The results showed that BMSCs-Exos under TNF-α stimuli exerted better effects on NPCs than BMSCs-Exos, which might be mitigated by the inhibition of miR-532–5p in BMSCs-Exos. The gain-of-function results suggested that the direct overexpression of miR-532–5p in NPCs could inhibit TNF-α-induced increase of apoptotic process, activation of apoptotic proteins, imbalance of anabolism/catabolism levels, and accumulation of collagen I. In addition, RASSF5 was demonstrated to be a target of miR-532–5p. Knockdown of RASSF5 could decrease the apoptotic cells and reduce the activated apoptotic protein levels in TNF-α-induced NPCs. Overall, these data indicate that exosomes from BMSCs may suppress TNF-α-induced apoptosis, ECM degradation, and fibrosis deposition in NPCs through the delivery of miR-532–5p via targeting RASSF5. This work provides a promising therapeutic strategy for the progress of IDD.
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JOURNAL OF CONTROLLED RELEASE
·
2020
·
IF 7.727
Xue Yang,Fang Gao,Wenan Zhang,Huipeng Li,Xinzhi Huang,Jiajia Wei,Jiayi Bian,Ying Yang,Chenggen Qian,Minjie Sun
Invasion and metastasis of tumor cells is one of the major obstacles in cancer therapy. The process of tumor metastasis and diffusion is coordinated by multiple pathways associated with chemokine signals and migration microenvironment. In our previous work, chemokine CXC receptor 4 (CXCR4) antagonists showed significant anti-metastatic effects by blocking the CXCR4/stromal cell-derived factor-1(SDF-1) axis in pancreatic cancer and breast cancer. Here, we proposed to achieve migration chain-treatment for metastatic tumors by introducing a cell adhesion molecules CD44 inhibitor (Star miR-34a) to deprive of cell migration capability on the basis of CXCR4 antagonism (cyclam monomer , CM). Dextrin modified 1.8 k PEI with CM-end was prepared to deliver therapeutic miR-34a (named DPC/miR-34a) for efficient anti-metastasis by downregulating adhesion protein CD44 and targeting the CXCR4/SDF-1 axis. Additionally, reduced expression of the anti-apoptotic protein Bcl2 caused by miR-34a could enhance the anti-tumor efficacy of DPC/miR-34a nanoplex administration. Compared with inhibition of the CXCR4/SDF-1 axis or CD44 expression, the multidimensional therapy (DPC/miR-34a) exhibited considerable suppression of cancer cell invasion as assessed by an in vitro cell invasion assay and in vivo anti-metastasis model. Moreover, DPC/miR-34a demonstrated a superior antitumor and anti-metastatic efficacy both in lung metastatic model and orthotopic MDA-MB-231 tumor models, thus providing an efficient approach for combating metastatic tumors.
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