Translational Cancer Research
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2019
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IF 1.07
Guangyuan Sun,Fei Guo,Xueliang Wu,Lei Han,Jun Xue
Background LncRNA cancer susceptibility candidate 9 (CASC9) is up-regulated in various cancers. In this study, we explored the role of CASC9 in colon cancer (CC). Methods The level of CASC9 in CC tissues, adjacent normal tissues, intestinal epithelial cells (HIEC) and CC cell lines was evaluated by qRT-PCR. HCT116 and SW480 CC cells were transfected with siCASC9. The cell growth and cell proliferation makers (Ki-67 and PCNA) were detected by CCK-8, colony formation and western blotting, respectively. The cell apoptosis and cell cycle were determined by flow cytometry. MicroRNA sponged by CASC9 was predicted by starBase and verified by dual-luciferase reporter assay. Further analyses were performed to investigate the role of CASC9 sponging the microRNA in CC cells by transfection or co-transfection of siCASC9 and miR-145-5p inhibitor. Results LncRNA CASC9 was high-expressed in CC cells and tissues, especially in CC at advanced TNM stages. In HCT116 and SW480 cells, knockdown of CASC9 suppressed cell proliferation, promoted cell apoptosis and arrested cell cycle at G0/G1 phase. Furthermore, CASC9 was observed to sponge and regulate the expression of miR-145-5p, which was down-regulated in CC tissues. Moreover, increased cell proliferation and decreased cell apoptosis and arrested cell cycle caused by miR-145-5p inhibitor were abrogated by the knockdown of CASC9. Conclusions LncRNA CASC9 is an oncogene in CC cells through sponging miR-145-5p. The findings in the current study provide a new understanding on CASC9 in CC.
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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产品关联
DOI
PubMed
高影响因子
Human Cell
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2025
·Vol. 39
·期 1
·27
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IF 3.1
Xu Jianfeng,Lei Deng,Xu Peng,Wang Yuqi,Li Zhupeng,Wu Jiacheng,Feng Weizhong,Zhou Junqing
Esophageal cancer (EC) remains a highly aggressive malignancy with limited therapeutic success, partly due to heterogeneous responses to neoadjuvant chemotherapy (NAC). Tumor-derived exosomes and tumor-associated macrophages play critical roles in shaping the immunosuppressive tumor microenvironment, but their crosstalk in EC chemoresistance remains unclear. In this study, we identified tumor-derived exosomal miR-145-5p as a potential predictor of poor NAC response. Elevated exosomal miR-145-5p levels were associated with increased M2 macrophage infiltration and enhanced expression of M2 markers in EC tissues. Mechanistically, miR-145-5p promoted M2 macrophage polarization through the suppression of transferrin receptor (TFRC) and subsequent disruption of iron uptake. Consequently, these tumor-promoting M2-polarized macrophages enhanced EC cell proliferation, migration, invasion, and cisplatin resistance. In vivo, macrophages overexpressing miR-145-5p facilitated tumor growth and markedly weakened the therapeutic effects of cisplatin. Overall, our findings reveal that EC cells utilize exosomal miR-145-5p to remodel macrophages into a pro-tumorigenic phenotype through TFRC-dependent iron metabolic reprogramming, contributing to malignant progression and chemoresistance. Exosomal miR-145-5p may represent a promising biomarker for NAC response and a therapeutic target to improve treatment outcomes in EC.
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
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2021
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IF 2.319
Lili TAN,Limin LIU,Jian YAO,Chenghao PIAO
Myocardial ischemia-reperfusion (I/R) injury is a common complication following reperfusion therapy that involves a series of immune or apoptotic reactions. Studies have revealed the potential roles of miRNAs in I/R injury. Herein, we established a myocardial I/R model in rats and a hypoxia/reoxygenation (H/R) model in H9c2 cells and investigated the effect of miR-145-5p on myocardial I/R injury. After 3 h or 24 h of reperfusion, LVESP, EF, and FS were obviously decreased, and LVEDP was increased. Meanwhile, I/R induced an increase in myocardial infarction area. Moreover, a decrease in miR-145-5p and increase in NOH-1 were observed following I/R injury. With this in mind, we performed a luciferase reporter assay and demonstrated that miR-145-5p directly bound to NOH-1 3’ UTR. Furthermore, miR-145-5p mimics decreased the levels of TNF-α, IL-1β, and IL-6 via OGD/R stimulation. Upregulation of miR-145-5p increased cell viability and reduced apoptosis accompanied by downregulation of Bax, cleaved caspase-3, cleaved PARP and upregulation of Bcl2. In addition, miR-145-5p overexpression increased SOD activity and reduced ROS and MDA content under OGD/R stress. Notably, NOH-1 could significantly abrogate the above effects, suggesting that it is involved in miR-145-5p-regulated I/R injury. In summary, our findings indicated that miR-145-5p/NOH-1 has a protective effect on myocardial I/R injury by inhibiting the inflammatory response and apoptosis.
研究领域:
心脏病学
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分子生物学
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炎症
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细胞凋亡
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DOI
PubMed
高影响因子
CELL CYCLE
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2021
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IF 4.534
Zhensong Jiang,Jianru Zhang
EXs (Exosomes) secreted by mesenchymal stem cells (MSCs) have the potential to treat spinal cord injury (SCI), this study aimed to further explore the therapeutic effect of EXs on SCI. Firstly, EXs were extracted from MSCs and analyzed with a transmission electron microscope. Next, MSCs with or without the miR-145-5p plasmid were injected into the SCI rat model, and then rat damage was evaluated by BBB score, HE staining and Nissl staining. And then Luciferase experiment verified the targeting relationship between miR-145-5p and TLR4. Furthermore, LPS-induced PC12 cells were established and incubated with Dil-labeled MSC-EXs to explore their effects on cell viability, apoptosis and inflammation through MTT, flow cytometry and ELISA, respectively. In addition, expressions of TLR4/NF-κB signaling pathway related factors were measured by qRT-PCR and Western blot. The results showed that after MSCs were successfully isolated, the existence of EXs in MSCs was confirmed. Moreover, MSC-EXs containing miR-145-5p improved functional recovery and reduced histopathological injury and inflammation in SCI rats. And MSC-EXs promoted miR-145-5p expression in spinal cord tissue and inhibited TLR4/NF-κB pathway activation in SCI rats. MSC-EXs inhibited LPS-induced inflammatory response and activation of the TLR4/NF-κB pathway in PC12 cells. In addition, we also found that miR-145-5p specifically targeted TLR4. TLR4 overexpression significantly reversed the effect of EX-miR-145-5p on maintaining PC12 cell viability, inhibiting apoptosis and inflammatory response, and activating TLR4/NF- κB pathway. In conclusion, mesenchymal stem cell-derived EXs containing miR-145-5p reduce inflammation in spinal cord injury by regulating the TLR4/NF-κB signaling pathway.
研究领域:
神经科学
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干细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
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